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Colorectal cancer (CRC) ranks among the top five most common malignant tumors worldwide and has a high mortality rate. Angiogenesis plays an important role in CRC progression; however, anti-angiogenesis therapy still has many limitations. Long non-coding RNAs (lncRNAs) participate in tumor progression by regulating vascular endothelial growth factor expression in metastatic CRC. Thus, targeting specific lncRNA may provide some new hope for anti-angiogenic strategies. Through analyzing data both from both clinical samples and The Cancer Genome Atlas database, we found that the lncRNA LINC01503 was specifically upregulated in CRC tissues, and was associated with tumor progression and a poor overall survival. We also demonstrated that LINC01503 enhanced the capacity of tube formation and migration of vascular endothelial cells, thus promoting CRC tumorigenesis by upregulating vascular endothelial growth factor A (VEGFA) expression in CRC cells. Mechanistically, LINC01503 promoted the expression of VEGFA by simultaneously regulating the stability of both the mRNA and VEGFA by binding to miR-342-3p and the chaperone HSP60. The upregulation of LINC01503 in CRC cells was attributed to the CREB-binding protein CBP/p300-mediated H3K27 acetylation of the LINC01503 promoter region. Taken together, our findings clarify the mechanism by which LINC01503 may promote CRC angiogenesis, implicating that LINC01503 may serve as a potential prognostic biomarker and therapeutic target for CRC.

Oral submucous fibrosis (OSF) is an oral potentially malignant disorder that is closely related to the habit of areca nut chewing. Long non-coding RNA (lncRNA) myocardial infarction-associated transcript ( MIAT ) has been identified as an essential regulator in the fibrosis progression. However, the role of MIAT in the development of OSF remains unknown. The transcriptomic profile showed that MIAT is significantly overexpressed in the OSF cohort, with a positive correlation to fibrotic markers. The silencing of MIAT expression in primary buccal mucosal fibroblasts (BMFs) markedly inhibited arecoline-induced myofibroblast transformation. Mechanistically, MIAT functioned as a miR-342-3p sponge and suppressed the inhibitory effect of miR-342-3p on SOX6 mRNA, thereby reinstating SOX6 expression. Subsequent RNA expression rescue experiments confirmed that MIAT enhanced resistance to apoptosis and facilitated myofibroblastic properties such as cell mobility and collagen gel contraction by regulating the miR-342-3p/SOX6 axis. Taken together, these results suggest that the abnormal upregulation of MIAT is important in contributing persistent activation of myofibroblasts in fibrotic tissue, which may result from prolonged exposure to the constituents of areca nut. Furthermore, our findings demonstrated that therapeutic avenues that target the MIAT/miR-342-3p/SOX6 axis may be a promising approach for OSF treatments.

Background: Casticin (CAS), a natural flavonoid found in Viticis Fructus, Viticis Cannabifoliae Fructus, and Semen Euphorbiae, shows anti-inflammatory activity and efficacy against various cancers. However, its effect on stemness associated with self-renewal in cervical cancer (CC) cells remains unclear, as well as the underlying mechanism., Purpose: The primary objective of this study was to examine the effect of CAS on CC stemness and to explore the underpinning regulatory mechanism., Methods: HeLa cells underwent treatment with varying concentrations of CAS (0, 10, 30, 100 nM). To evaluate the impacts of CAS on CC stemness and tumorigenicity, sphere- and colony-formation assays and a xenograft model were employed. The study involved screening for changes in miRNAs and their target genes. The miRNA array identified an upregulation in miRNAs, whereas the mRNA array detected a downregulation of specific target genes. The latter genes were found to regulate stem cell-related genes through miR-342-3p in HeLa cells administered CAS. Next, whether miR-342-3p directly targets FOXM1 when upregulated by CAS was assessed by the luciferase reporter assay. qRT-PCR was performed to analyze miR-342-3p expression. Additionally, immunoblotting was conducted to assess the protein amounts of FoxM1 and stemness-related factors (CD133, CD49f, Nanog, and Sox2). Function rescue experiments were conducted to determine the mechanism of CAS in stemness regulation. These experiments involved utilizing a miR-342-3p inhibitor and overexpressing FOXM1 in HeLa cells., Results: CAS decreased in vitro stemness, suppressing sphere- and colony-formation capabilities of CC. It also dose-dependently downregulated the expression of stemness-associated proteins, including CD133, CD49f, Nanog, and Sox2. Moreover, CAS inhibited in vivo carcinogenesis, remarkably reducing tumor growth in mice bearing HeLa cell xenografts. Analysis revealed downregulated FOXM1 expression in HeLa cells treated with CAS. In the luciferase reporter assay, miR-342-3p was found to directly target FOXM1 in CAS-treated HeLa cells. Additionally, miR-342-3p inhibitor transfection successfully rescued CAS' suppressive impact on stemness. Furthermore, overexpression of FOXM1 did not induce changes in miR-342-3p expression. However, it effectively rescued CAS' suppressive effects on stemness. Moreover, CAS also inhibited stemness, upregulated miR-342-3p, and lowered FOXM1 expression in the SiHa cell line., Conclusion: CAS suppresses self-renewal-associated stemness by targeting FOXM1 via miR-342-3p upregulation. These findings suggest CAS is promising as a novel therapeutic candidate in CC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier GmbH.)

Podocyte damage plays a crucial role in the occurrence and development of diabetic nephropathy (DN). Accumulating evidence suggests that dysregulation of transcription factors plays a crucial role in podocyte damage in DN. However, the biological functions and underlying mechanisms of most transcription factors in hyperglycemia-induced podocytes damage remain largely unknown. Through integrated analysis of data mining, bioinformatics, and RT-qPCR validation, we identified a critical transcription factor forkhead box F1 (FOXF1) implicated in DN progression. Moreover, we discovered that FOXF1 was extensively down-regulated in renal tissue and serum from DN patients as well as in high glucose (HG)-induced podocyte damage. Meanwhile, our findings showed that FOXF1 might be a viable diagnostic marker for DN patients. Functional experiments demonstrated that overexpression of FOXF1 strikingly enhanced proliferation, outstandingly suppressed apoptosis, and dramatically reduced inflammation and fibrosis in HG-induced podocytes damage. Mechanistically, we found that the downregulation of FOXF1 in HG-induced podocyte damage was caused by DNMT1 directly binding to FOXF1 promoter and mediating DNA hypermethylation to block FOXF1 transcriptional activity. Furthermore, we found that FOXF1 inhibited the transcriptional expression of miR-342-3p by binding to the promoter of miR-342, resulting in reduced sponge adsorption of miR-342-3p to E2F1, promoting the expression of E2F1, and thereby inhibiting HG-induced podocytes damage. In conclusion, our findings showed that blocking the FOXF1/miR-342-3p/E2F1 axis greatly alleviated HG-induced podocyte damage, which provided a fresh perspective on the pathogenesis and therapeutic strategies for DN patients., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To explore the effects of microRNA-342-3p/Mg 2+ Mn 2+ -dependent protein phosphatase 1E (miR-342-3p/PPM1E) on the proliferation, migration, and invasion of clear cell renal cell carcinoma (ccRCC) cells., Methods: The gene chips GSE12105, GSE23085, GSE66271, and GSE66270 were searched, and the relationship between miR-342-3p, PPM1E, and the clinical malignant phenotypes of ccRCC was analyzed. ACHN and 769-P cells were transfected with miR-342-3p inhibitor. The effects of miR-342-3p on cell proliferation, migration, and invasion were examined. ACHN cell line with stable and high expression of miR-342-3p was constructed, and the tumorigenicity of the cell line in BALB/c nude mice was observed. The targeted relationship between miR-342-3p and PPM1E was verified by dual-luciferase reporter gene assay. The cells were transfected with miR-342-3p mimic and pcDNA- PPM1E plasmids to observe whether PPM1E could reverse the effects of miR-342-3p overexpression on the proliferation, migration, and invasion of the cells., Results: The expression of miR-342-3p was upregulated in ccRCC, and there were significant differences among patients with tumors of different T stages and G stages and those with different prognoses ( P <0.05). The overall survival in the miR-342-3p high-expression group was significantly shorter than that in the low-expression group ( P <0.05). Compared with those in the miR-NC group, the miR-342-3p level was significantly downregulated in the inhibitor group, and the cell proliferation ability and the numbers of migrating and invading cells were also significantly decreased ( P <0.05). Compared with the miR-NC group, miR-342-3p group had significantly increased volume and mass of tumor tissues and miR-342-3p level, but significantly decreased level of PPM1E mRNA ( P <0.05). The expression of PPM1E was downregulated in ccRCC, and there were significant differences among patients with tumors of different M stages, N stages, and G stages, and different recurrence statuses ( P <0.05). The miR-342-3p could inhibit the expression of PPM1E in a targeted way. Compared with the miR-NC group, the miR-342-3p group had significantly increased cell proliferation ability and increased numbers of migrating and invading cells ( P <0.05). However, PPM1E could reverse the promotion effect of miR-342-3p mimic on ccRCC cells ( P <0.05)., Conclusion: The miR-342-3p can inhibit PPM1E expression in a targeted way, and thus promotes the proliferation, migration, and invasion of ccRCC cells., Competing Interests: 利益冲突　所有作者均声明不存在利益冲突, (© 2024《四川大学学报（医学版）》编辑部 版权所有Copyright ©2024 Editorial Office of Journal of Sichuan University (Medical Sciences).)

Background: To explore the diagnostic role and potential mechanism of serum lncRNA UCA1 in Alzheimer's disease (AD)., Methods: UCA1 concentration was determined using quantitative RT-PCR. The receiver operating characteristic curve was plotted to assess the diagnostic value. Cell viability and apoptotic capacity were assessed by cell counting kit-8 (CCK-8) and flow cytometry. Water maze experiments were used to test cognitive function in mice. The target genes of UCA1 were identified with a dual luciferase reporter assay. Functional and pathway analysis of miR-342-3p target genes was determined using enrichment analysis., Results: The concentration of UCA1 was elevated in the AD group and represented a diagnostic possibility of AD. The silenced UCA1 reduced the roles of Aβ on viability and apoptosis of SH⁃SY5Y cells by sponging miR-342-3p. The impaired cognitive impairment was partly recovered by the knockdown of the UCA1/miR-342-3p axis. Potential targets of miR-342-3p were enriched in function and pathways related to AD progression., Conclusion: The UCA1/miR-342-3p axis contributed to the occurrence of AD by regulating cognitive ability., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Coronary slow flow (CSF) is characterized by slow progression of coronary angiography without epicardial stenosis. The aim of this study was to explore the potential biomarkers and regulatory mechanism for CSF. Peripheral blood mononuclear cells from 3 cases of CSF and 3 healthy controls were collected for high-throughput sequencing of mRNA and miRNA, respectively. The differentially expressed mRNAs (DE-mRNAs) and miRNAs (DE-miRNAs) was identified. A total of 117 DE-mRNAs and 32 DE-miRNAs were obtained and they were mainly enriched in immune and inflammatory responses. Twenty-six DE-mRNAs were the predicted target genes for miRNAs by RAID, and then the regulatory network of 15 miRNAs were constructed. In addition, through the PPI network, we identified the three genes (FPR1, FPR2 and CXCR4) with larger degrees as hub genes. Among them, FPR1 was regulated by hsa-miR-342-3p, hsa-let-7c-5p and hsa-miR-197-3p and participated in the immune response. Finally, we validated the differential expression of hub genes and key miRNAs between 20 CSF and 20 control. Moreover, we found that miR-342-3p has a targeted regulatory relationship with FPR1, and their expression is negatively correlated. Then we established a hypoxia/reoxygenation (H/R) HUVEC model and detected FPR1, cell proliferation and apoptosis. Transfection with miR-342-3p mimics can significantly promote the proliferation of HUVEC under H/R conditions. FPR1 were associated with CSF as a biomarker and may be regulated by miR-342-3p potential biomarkers., (© 2024. The Author(s).)

Long noncoding RNAs (lncRNAs) play important roles in modulating the tumorigenesis and progression of malignant tumors. LINC02086 is a newly identified oncogene associated with tumorigenesis, but its role in pancreatic cancer (PC) has not been fully elucidated. In this study we examined the expression levels of LINC02086, miR-342-3p, and CA9 in PC. The relationship of ferroptosis with these factors was analyzed by detecting the expression levels of Fe 2+ , reactive oxygen species (ROS), and ferroptosis marker proteins. The expression of these genes was altered to observe their effects on cell proliferation, migration, and invasion ability. Bioinformatics was used to predict target genes, and the binding relationship was verified luciferase reporter assay. Finally, the function of LINC02086 was evaluated in vivo. The findings suggest that LINC02086 is highly expressed in PC tissues and cell lines and is correlated with a poor prognosis. In vitro experiments demonstrated that LINC02086 knockdown promoted ferroptosis in PC cells to suppress their malignant phenotype. LINC02086 acts as a competitive endogenous RNA that adsorbed miR-342-3p. miR-342-3p hinders the malignant progression of PC by promoting ferroptosis. In addition, miR-342-3p targets CA9 and affects its function. Further mechanistic studies revealed that LINC02086 inhibits ferroptosis and promotes PC progression by acting as a sponge for miR-342-3p to upregulate CA9 expression. In vivo experiments further confirmed this mechanism. Taken together, LINC02086 upregulates CA9 expression by competitively binding with miR-342-3p, thereby inhibiting ferroptosis in PC cells and promoting their malignant phenotype. The results of our study provide new insights into how LINC02086 contributes to the progression of PC., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

LINC00624 is a long noncoding RNA (lncRNA) which was seldom investigated before. The goal of our study is to clarify the expression and underlying network of LINC00624 in hepatocellular carcinoma (HCC). Here, both HCC and normal living cell lines were employed. Real-time quantitative PCR and western blot were used to determine the pattern of genes and proteins. Colony formation, flow cytometry and western blot tests were used to determine cell proliferation and apoptosis, respectively. Dual luciferase was used to verify molecule-molecule interactions. LINC00624 expression was increased in HCC cell lines and miR-342-3p was decreased. Elimination of LINC00624 increased proliferation while decreasing cell apoptosis. LINC00624 acted as a molecular sponge for miR-342-3p, hence facilitating DNAJC5 expression. Functional tests demonstrated that miR-342-3p suppression could reverse the effect of LINC00624 silence and overexpression of DNAJC5 significantly mitigated the biological consequences of miR-342-3p. These finding demonstrated that LINC00624 aggravated HCC progression by modulating proliferation and apoptosis via targeting miR-342-3p/DNAJC5 axis. These data support that inhibition of LINC00624 may a potential treatment strategies of HCC., (© 2024 Wiley Periodicals LLC.)

Background: Chronic renal failure (CRF) is the result of kidney damage. Puerarin is a flavonoid with specific nephroprotective effect, but its effect on CRF needs further research. This study explored the effect of puerarin on CRF and the potential molecular mechanism., Methods: Adenine was used to establish an in vivo CRF model in rats, and rats were intragastrically administered with puerarin at a dose of 400 mg/kg body weight once a day from day 1 to day 28. Hematoxylin and eosin (HE) and Masson staining were used to observe the morphology and fibrosis of kidney tissue. Lipopolysaccharide (LPS) (400 ng/mL)/H 2 O 2 (200 µM) was applied to human kidney 2 (HK-2) cells to construct an in vitro CRF model. Enzyme-linked immunosorbent assay (ELISA) was performed to validate interleukin (IL)-1β and IL-18 levels. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) was performed to detect microRNA (miR)-342-3p levels. Transforming growth factor beta (TGF-β)1, SMAD2, SMAD3, and pyroptosis marker proteins were detected by Western blot. The interaction between miR-342-3p and TGF-β/SMAD was determined by a dual-luciferase reporter gene assay. Cell Counting Kit-8 (CCK-8) assay was utilized to determine cell viability., Results: In the CRF model, puerarin alleviated renal injury and fibrosis and reduced creatinine (Cr) and blood urea nitrogen (BUN) levels. At the same time, miR-342-3p was downregulated, while the TGF-β/SMAD axis was activated and levels of IL-1β and IL-18 were increased. After treatment of CRF rats with puerarin, the expression level of miR-342-3p was increased, the TGF-β/SMAD axis was inhibited, and the secretion of IL-1β and IL-18 was decreased. MiR-342-3p directly bound to and negatively regulated the expression of TGF-β1, SMAD2, and SMAD3. In the in vitro CRF model, miR-342-3p inhibited HK-2 cell pyroptosis by inhibiting the TGF-β/SMAD axis., Conclusion: Puerarin reduced renal injury and pyroptosis in CRF rats by targeting the miR-342-3p/TGF-β/SMAD axis., (© 2023. The Author(s) under exclusive licence to The Genetics Society of Korea.)

Background: Tendon-derived stem cells (TDSCs) are proposed as a potential cell-seed for the treatment of tendon injury due to their tenogenic differentiation potential. In this work, we defined the action of long non-coding RNA (lncRNA) muscle differentiation 1 (LINCMD1) in tenogenic differentiation of human TDSCs (hTDSCs)., Methods: Quantitative real-time PCR (qRT-PCR) was used to assess the levels of LINCMD1, microRNA (miR)-342-3p, and early growth response-1 (EGR1) mRNA. Cell proliferation was detected by the XTT colorimetric assay. Protein expression was quantified by western blot. hTDSCs were grown in an osteogenic medium to induce osteogenic differentiation, and the extent of osteogenic differentiation was assessed by Alizarin Red Staining (ARS). The activity of alkaline phosphatase (ALP) was measured by the ALP Activity Assay Kit. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were used to evaluate the direct relationship between miR-342-3p and LINCMD1 or EGR1., Results: Our results showed that enforced expression of LINCMD1 or suppression of miR-342-3p accelerated the proliferation and tenogenic differentiation and reduced osteogenic differentiation of hTDSCs. LINCMD1 regulated miR-342-3p expression by binding to miR-342-3p. EGR1 was identified as a direct and functional target of miR-342-3p, and knockdown of EGR1 reversed the effects of miR-342-3p suppression on cell proliferation and tenogenic and osteogenic differentiation. Furthermore, the miR-342-3p/EGR1 axis mediated the regulation of LINCMD1 on hTDSC proliferation and tenogenic and osteogenic differentiation., Conclusion: Our study suggests the induction of LINCMD1 in tenogenic differentiation of hTDSCs through miR-342-3p/EGR1 axis.

Purpose: Dysregulated circular RNAs (circRNAs) have shown crucial modulatory functions in tumorigenesis, containing non-small cell lung cancer (NSCLC). The purpose of this study was to explore the biological functions and regulatory theory of circ&#95;0006220 in NSCLC., Methods: Reverse transcription-quantitative polymerase chain reaction and Western blot assay were conducted to measure RNA and protein expression, respectively. A total of 73 cases of NSCLC tumor samples were collected for expression analysis, and A-549 and NCI-H1299 cell lines were used for functional experiments. Cell proliferation was assessed by cell counting kit-8 assay, colony formation assay, 5-ethynyl-2'-deoxyuridine assay, and flow cytometry. Cell apoptosis, motility, and angiogenesis ability were analyzed by flow cytometry, transwell assays, and capillary-like network formation assay. Dual-luciferase reporter assay and RNA immunoprecipitation assay were conducted to verify the target relationships., Results: Circ&#95;0006220 was highly expressed in NSCLC tissues and cell lines. Circ&#95;0006220 silencing inhibited the proliferation, migration, invasion, and angiogenesis but induced the apoptosis of NSCLC cells. Circ&#95;0006220 acted as a microRNA-342-3p (miR-342-3p) sponge, and circ&#95;0006220 knockdown-induced changes on the phenotypes of NSCLC cells were largely overturned by the knockdown of miR-342-3p. miR-342-3p interacted with the 3' untranslated region of glutamic-oxaloacetic transaminase 2 (GOT2), and GOT2 overexpression largely diminished miR-342-3p overexpression-mediated influences in NSCLC cells. Circ&#95;0006220 could up-regulate GOT2 expression by sponging miR-342-3p., Conclusion: Circ&#95;0006220 promoted the malignant behaviors of NSCLC cells through mediating the miR-342-3p/GOT2 regulation cascade.

Purpose: The aim of this study was to investigate the diagnostic ability and prognostic value of miR-342-3p in SLE patients by detecting the expression level of serum miR-342-3p in SLE patients., Patients and Methods: The expression level of serum miR-342-3p in all subjects was determined by qRT-PCR technology, and the correlation of miR-342-3p with SLEDAI scores was evaluated using Spearman correlation coefficient. The diagnostic value of miR-342-3p in SLE was assessed using ROC curve. The prognostic value of miR-342-3p in SLE patients was analyzed by Kaplan-Meier survival curve and multivariate COX regression., Results: The qRT-PCR results showed that the expression level of serum miR-342-3p in SLE patients was significantly lower than that in healthy controls ( P < 0.001). Serum miR-342-3p expression level was negatively correlated with SLEDAI scores (r = - 0.810, P < 0.001). The ROC curve suggested that serum miR-342-3p expression level was discriminative between SLE patients and healthy controls. Survival analysis results indicated that SLE patients with low serum miR-342-3p expression had a higher probability of poor prognosis of SLE (Log rank P = 0.003)., Conclusion: The expression level of serum miR-342-3p was valuable in the diagnosis of SLE. Meanwhile, the low expression level of serum miR-342-3p was associated with the poor prognosis of SLE., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 You et al.)

Background: Epileptogenesis is a process that results in neurons firing abnormally, causing seizures. Increasing evidence has shown that miRNAs expressed in the epileptic hippocampus are involved in epileptogenesis. We demonstrated the expression changes of miRNAs that may be effective in epileptogenesis in silico analysis in the kindling model created with Pentylenetetrazole (PTZ). Thus, we aimed to identify the target genes responsible for epileptogenesis., Methods and Results: Fifteen male Wistar-albino rats (200-230 g) were randomly divided into two groups control (n = 6) and PTZ (n = 9). The control group received 0.5 ml saline, and the PTZ group (35 mg/kg i.p.) intraperitoneally (i.p.) (11 times, every other day) to induce tonic-clonic seizures. Seizures were observed and scored 30 min after PTZ injection. After the last dose of PTZ (75 mg/kg) administration, the hippocampus tissues of the rats were removed by anesthesia. Analysis of miRNAs was performed with the Affymetrix gene chip miRNA sequence (728 miRNA) and confirmed by the Real-Time Polymerase Chain Reaction (Real-Time PCR) method (29 miRNAs). We evaluated the expression change of the target gene of miRNA, whose expression change was detected using in silico analysis, by q-RT PCR. Eight miRNAs with changes in expression were detected. Of these miRNAs, miR-342-p was downregulated in the PTZ group and was statistically significant (p < 0.005). Ultimately, we determined that the target gene of miR-342-p is a metabotropic glutamate receptor 2 (GRM2) and that GRM2 expression is upregulated., Conclusions: Downregulation of miR-342-3p in the PTZ kindling model may result in the upregulation of GRM2., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Objective: To investigate the expression level of miR-342-3p in peripheral blood mononuclear cells (PBMCs) of patients with rheumatoid arthritis (RA) and its effect on inflammatory response and migration of synovial fibroblasts in RA (RA-FLS)., Methods: PBMCs were collected from 30 healthy individuals and 50 RA patients for detecting the expression of miR-342-3p, and its correlation with the clinical indicators RF, ESR, anti-CCP, hs-CRP, C3, DAS-28, SAS, and SDS was analyzed. In RA-FLS cultures, the effect of transfection of miR-342-3p mimics and inhibitor on TNF- α -induced inflammatory response of the cells was evaluated by detecting the expressions of IL-1β, IL-6, IL-10, and TNF- α using ELISA. CCK8 assay and Transwell assay were used for detecting the changes in cell viability and migration ability of the synovial cells., Results: In RA patients, the expression level of miR-342-3p was significantly lowered in the PBMCs ( P < 0.05) with an area under the ROC curve of 97.53% and showed inverse correlations with RF ( r =-0.321), ESR( r =-0.284), anti-CCP ( r =-0.355), hs-CRP ( r =-0.320), C3 ( r =-0.294), DAS-28 ( r =-0.395), SAS ( r =-0.366), and SDS ( r =-0.397) (all P < 0.05); a low expression of miR-342-3p was strongly associated with elevated levels of anti-CCP, DAS-28, SDS, and SAS (all with a rule support greater than 85%, confidence greater than 88%, and lift greater than 1). In cultured RA-FLS, TNF- α stimulation significantly increased the cell viability ( P < 0.05), upregulated the expressions of IL-1β, IL-6, and TNF- α , and lowered the expression of IL-10 ( P < 0.05). These changes were significantly suppressed by transfection of the cells with miR-342-3p mimics ( P < 0.05) but enhanced by transfection with miR-342-3p inhibitor ( P < 0.05)., Conclusion: The expression of miR-342-3p is decreased in the PBMCs of RA patients. A lowered expression of miR-342-3p contributes to the pathogenesis of RA by promoting inflammatory responses and migration of RA-FLS.

Due to its difficulty in early diagnosis and lack of sensitivity to chemotherapy and radiotherapy, renal cell carcinoma (RCC) remains to be a frequent cause of cancer-related death. Here, we probed into new targets for its early diagnosis and treatment for RCC. microRNA (miRNA) data of M2-EVs and RCC were searched on the Gene Expression Omnibus database, followed by the prediction of the potential downstream target. Expression of target genes was measured via RT-qPCR and Western blot, respectively. M2 macrophage was obtained via flow cytometry with M2-EVs extracted. The binding ability of miR-342-3p to NEDD4L and to CEP55 ubiquitination was studied with their roles in the physical abilities of RCC cells assayed. Subcutaneous tumor-bearing mouse models and lung metastasis models were prepared to observe in vivo role of target genes. M2-EVs induced RCC growth and metastasis. miR-342-3p showed high expression in both M2-EVs and RCC cells. M2-EVs carrying miR-342-3p promoted RCC cell abilities to proliferate, invade and migrate. In RCC cells, M2-EV-derived miR-342-3p could specifically bind to NEDD4L and consequently elevate CEP55 protein expression via suppressing NEDD4L, thereby exerting tumor-promoting effects. CEP55 could be degraded by ubiquitination under the function of NEDD4L, and miR-342-3p delivered by M2-EVs facilitated the RCC occurrence and development by activating the PI3K/AKT/mTOR signaling pathway. In conclusion, M2-EVs promote RCC growth and metastasis by delivering miR-342-3p to suppress NEDD4L and subsequently inhibit CEP55 ubiquitination and degradation via activation of the PI3K/AKT/mTOR signaling pathway, strongly driving the proliferative, migratory and invasive of RCC cells., Competing Interests: The authors declare that they have no conflicts of interest to report regarding the present study., (© 2022 Feng et al.)

Long noncoding RNAs (lncRNAs) are important players in laryngeal squamous cell carcinoma (LSCC). However, the function of the long noncoding RNA small nucleolar RNA host gene 20 (SNHG20) in LSCC is hardly known. We therefore analyzed the role of this lncRNA in LSCC. Our data showed that SNHG20 was significantly overexpressed in LSCC cell lines and human LSCC tissue. SNHG20 significantly promoted cell proliferation, migration and invasion of LSCC cells. The actions of SNHG20 are likely mediated by miR-342-3p expression, which results in increased expression of MTDH. Finally, the results of in vivo models confirmed that SNHG20 promotes LSCC progression through modulating miR-342-3p and MTDH expression. Taken together, our study demonstrates that SNHG20/miR-342-3p/MTDH axis participates in LSCC progression., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s).)

MicroRNAs (miRNAs) play vital roles in the development of oocytes and ovarian follicles. We have previously shown differential expression of miR-342-3p during yak oocyte maturation. In this study, we investigated the role of miR-342-3p in meiotic maturation of yak oocytes and the underlying mechanism. The profile of ovarian DNA methyltransferase 1 (DNMT1) expression was investigated in yak by RT-qPCR and western blot analyses. The pattern of Dnmt1 expression in various meiotic stages (GV stage, MI stage and MII stage) of yak oocyte maturation was then measured by immunofluorescence staining. The interaction between Dnmt1 and miR-342-3p was verified by dual-luciferase reporter assay. Finally, miR-342-3p inhibitors were microinjected into yak cumulus-oocyte complex to evaluate the effects on oocyte maturation. MiR-342-3p expression was upregulated in oocytes during meiotic maturation, with significantly higher levels in the MII stage compared with the GV- and MI stages (p < .05), whereas the opposite pattern of Dnmt1 expression was detected. In the period to sexual maturity (3-year-old), DNMT1 showed an age-related pattern of ovarian expression at both the gene and protein levels. Immunohistochemistry analysis also indicated maturation-stage-related differences in DNMT1 expression in the ovarian follicles and corpus luteum, with expression predominantly detected in cumulus cells and oocytes. MiR-342-3p inhibitors effectively upregulated Dnmt1 expression and significantly inhibited oocyte meiotic maturation. Taken together, our results indicate that miR-342-3p plays a vital role in the meiotic maturation of yak oocytes by targeting the 3'-untranslated regions (UTR) of Dnmt1 and provide a new perspective on the mechanism of this process., (© 2022 Wiley-VCH GmbH.)

Background: The mesenchymal stem cell-derived exosome (MSCs-exo) carrying microRNAs have been proved to regulate tumor biological activities. Clarifying molecular mechanism and identifying predictive microRNAs will be of great value in anti-tumor therapy improvement., Objective: We aimed to investigate the regulatory role of microRNA-342-3p (miR-342-3p) in MSCs-exo on breast cancer., Methods: Breast cancer tissues and cell lines were used to evaluate miR-342-3p expression in patients with or without lymph node/distal organ metastasis. The impact of MSCs-exo expression on tumor cell chemo-resistance and invasion/migration was measured. Dual-luciferase reporter gene assay was applied to identify binding site. Inhibitor of differentiation 4 (ID4) siRNA and miR-342-3p inhibitor transfection was conducted to further explore the miR-342-3p/ID4 axis on chemo-resistance and metastasis of breast cancer cells., Results: Breast cancer cells revealed significantly lower level of miR-342-3p in patients with metastatic diseases. miR-342-3p suppressed invasive and chemo-resistant behavior of breast cancer tumor cells. Binding site between miR-342-3p and ID4 was proved. ID4 could reverse the influence of miR-342-3p on chemo-resistance. The tumor inhibition effect of IDA siRNA in vivo was also identified., Conclusions: This study demonstrated that miR-342-3p acted as potential tumor suppressor by inhibiting metastasis and chemo-resistance of breast cancer cells through targeting ID4. This study might provide potential therapy targets for the treatment of breast cancer., (© 2021. The Author(s) under exclusive licence to The Genetics Society of Korea.)

Hepatocellular carcinoma (HCC) is a highly mortal cancer that could be treated by radiotherapy. DNA damage response (DDR) is a vital factor affecting cancer development after radiotherapy. Long non-coding RNAs (lncRNAs) have been revealed to regulate DNA damage response and repair in cancer cells. Nevertheless, the function of long intergenic non-protein coding RNA 1134 (LINC01134) has not been explored in DDR. In this study, we targeted digging into the function of LINC01134 in DDR and exploring the underlying mechanism in HCC cells. RT-qPCR was employed to measure LINC01134 expression, and we found LINC01134 was significantly upregulated in HCC cells. Functional analysis suggested that LINC01134 depletion attenuated radioresistance of HCC cells by facilitating DNA damage. In vivo assays demonstrated LINC01134 depletion hindered HCC tumor growth. Mechanism assays unveiled LINC01134 sequestered microRNA-342-3p (miR-342-3p) and recruited insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) protein to modulate mitogen-activated protein kinase 1 (MAPK1) expression, consequently activating MAPK signaling pathway. Rescue assays validated the LINC01134/miR-342-3p/MAPK1 axis in the radio-resistant HCC cells. In conclusion, LINC01134 might be identified to be a useful biomarker for the therapy of HCC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Wang, Rong, Dai, Qin, Wang and Geng.)

Background: Nasopharyngeal carcinoma (NPC) is a deadly cancer, mainly presenting in southeast and east Asia. Long noncoding RNAs (lncRNAs) play essential roles in cancer progression. Exosomes are critical for intercellular communication. Thus, the aim of this study was to identify the functional lncRNAs in NPC and its relevant mechanisms., Methods: Data from public databases were utilized to screen for functional lncRNAs in NPC. Functional and mechanical experiments were performed to determine the role of lncRNAs in NPC and its relative molecular mechanisms. Exosomes derived from NPC cells were isolated to determine their function in tumor-associated macrophages., Results: LncRNA TP73-AS1 was increased in NPC cells and tissues and was associated with a poor prognosis. TP73-AS1 overexpression promoted proliferation, colony formation, and DNA synthesis of NPC cells while TP73-AS1 knockdown showed opposite roles. TP73-AS1 could directly bind with miR-342-3p. MiR-342-3p overexpression attenuated the effect of TP73-AS1 in NPC cells. Furthermore, TP73-AS1 was transferred by exosomes to promote M2 polarization of macrophages. Lastly, exosomal TP73-AS1 enhanced the motility and tube formation of macrophages., Conclusions: Together, this study suggests that TP73-AS1 promotes NPC progression through targeting miR-342-3p and exosome-based communication with macrophages and that TP73-AS1 might be an emerging biomarker for NPC., (© 2021. The Author(s).)

Objective: This study aims to explore the effects of miR-342-3p on liver cancer stem cells (LCSC) and related mechanism., Methods: LCSC were sorted using immunomagnetic beads and flow cytometry was used to determine CD133+ and CD133- sorted cells. The self-renewal ability and growth ability of LCSC were measured by tumor spheroid formation assay and soft agar colony formation assay. Protein and mRNA expressions of CD44, ALDH1, Bmi1, Sox2 and Oct4 were detected by western blot and quantitative PCR. The relationship between miR-342-3p and HDAC7 was analyzed by dual-luciferase assay. The acetylation level of H3 protein was measured by acetyl Lysine antibody., Results: miR-342-3p overexpression in LCSC lead to lower tumor volume, reduced tumor spheroid formation and agar colony formation rates, as well as lower mRNA and protein expressions of CD44, ALDH1, Bmi1, Sox2, and Oct4. Dual-luciferase reporter assay confirmed HDAC7 as a target gene of miR-342-3p. Inhibition of HDAC7 or overexpression of PTEN suppressed the carcinogenicity and stemness of LCSC. PTEN expression was increased in sh-HDAC7 group and decreased in pcDNA3.1-HDAC7 group. HDAC7 promoted H3 deacetylation and inhibited PTEN expression. Overexpression of HDAC7 or silencing of PTEN could reverse the inhibitory effect of overexpression of miR-342-3p on LCSC carcinogenicity and cell stemness., Conclusion: MiR-342-3p inhibited LCSC oncogenicity and cell stemness by promoting PTEN and inhibiting HDAC7., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Long non-coding RNAs (lnc-RNAs) and microRNAs (miRNAs) play key roles in the development of stroke. However, the role of lncRNA FTX in stroke is limited known., Methods: Real-time polymerase chain reaction (real-time PCR) assays were used to measure the expression of lncRNA FTX, miR-342-3p and SPI1. Western blot assays were employed to examine SPI1 protein expression. The cell viability was measured by CCk8 assay. Cell migration was detected by wound healing assays and transwell assays. Angiogenesis was evaluated by matrigel tube formation assays. The interaction between lncRNA FTX, miR-342-3p and SPI1 was confirmed by site-directed mutagenesis and luciferase assays., Results: The expression of lncRNA FTX was down-regulated in blood sample from stroke patients, MAO mice tissues and OGD/R treated BMECs. Overexpression of lncRNA FTX could increase the cell viability, migration and angiogenesis in OGD/R treated BMECs. LncRNA FTX could act as a ceRNA for miR-342-3p. Furthermore, miR-342-3p inhibition increased migration and angiogenesis in OGD/R-induced BMECs. Dual-luciferase reporter assay verified that SPI1 was a target of miR-342-3p., Conclusion: In summary, lncRNA FTX enhanced the angiogenesis in stroke by acting as a sponge of miR-342-3p to regulate the expression of SPI1 level., Competing Interests: The authors declare that they have no competing interests., (© 2021 Gao and Wang.)

Purpose: Glioma has been categorized as the most common primary malignant brain tumor. Long non-coding RNA SNHG7 (lncRNA SNHG7) has been recognized in various cancers as a possible oncogene. In this study, the effect of SNHG7 on glioma cells was investigated., Materials and Methods: Thirty glioma tissues and adjacent normal tissues were collected. Pc-SNHG7, sh-SNHG7, miR-342-3p mimic and miR-342-3p inhibitor were transfected into the glioma cells. Cell Counting Kit-8, Transwell and scratch assay evaluated glioma cells viability, invasion and migration, respectively. TargetScan, Starbase and dual-luciferase reporter were used to predict and confirm the target genes and potential binding sites of SNHG7, miR-342-3p and AKT2. Relative miR-342-3p and AKT2 expressions were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Pearson's analysis was adopted for correlation analysis between SNHG7, miR-342-3p and AKT2., Results: SNHG7 expressions in glioma tissues and cells were increased, upregulation of SNHG7 promotes cell viability, invasion and migration. SNHG7 was shown to bind with miR-342-3p, and upregulating SNHG7 reduced miR-342-3p expression. AKT2 was the target gene of miR-342-3p, and miR-342-3p expression was decreased while AKT2 expression was increased in glioma tissues. High expression of miR-342-3p inhibited cell viability, invasion and migration and reduced AKT2 expression, whereas low expression of miR-342-3p did the opposite effect., Conclusions: Upregulating SNHG7 might promote glioma cells viability, migration and invasion with the regulation of decreasing miR-342-3p level and increasing AKT2 level.

Background: Accumulating evidence demonstrated that circular RNAs (circRNAs) play pivotal regulatory roles in the pathology of cancers. Disclosing the roles and molecular mechanisms of circRNAs in tumorigenesis and development is essential to identify novel diagnostic and therapeutic targets. In this study, we explored the role of circVAPA in non-small-cell lung cancer (NSCLC) progression and its associated mechanism., Methods: The expression level of RNA was analyzed by real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferation was assessed by MTT assay and colony-forming assay. Cell apoptosis was analyzed by flow cytometry. Cell migration and invasion were assessed by transwell assays. Dual-luciferase reporter, RNA pull-down, and RNA immunoprecipitation (RIP) assays were used to test the intermolecular interactions. The role of circVAPA was assessed in vivo. And xenograft tumor tissues were analyzed by immunohistochemistry (IHC) staining., Results: CircVAPA expression was upregulated in NSCLC tissues and cell lines, and a high level of circVAPA was associated with a poor prognosis of NSCLC patients. CircVAPA silencing suppressed the proliferation, migration, and invasion and induced the apoptosis of NSCLC cells. CircVAPA served as a molecular sponge for microRNA-342-3p (miR-342-3p). miR-342-3p interference largely reversed circVAPA knockdown-mediated anti-tumor effects in NSCLC cells. Zinc finger E-box-binding homeobox 2 (ZEB2) was a target of miR-342-3p, and miR-342-3p overexpression suppressed the malignant behaviors of NSCLC cells largely by downregulating ZEB2. CircVAPA silence repressed xenograft tumor growth in vivo, and IHC assay confirmed that circVAPA silence restrained the proliferation and metastasis but induced the apoptosis of NSCLC cells in vivo., Conclusion: CircVAPA contributes to the progression of NSCLC by binding to miR-342-3p to upregulate ZEB2. CircVAPA/miR-342-3p/ZEB2 axis might be a novel potential target for NSCLC treatment., (© 2021. The Author(s).)

Purpose: Physical activity is associated with altered levels of circulating microRNAs (ci-miRNAs). Changes in miRNA expression have great potential to modulate biological pathways of skeletal muscle hypertrophy and metabolism. This study was designed to determine whether the profile of ci-miRNAs is altered after different approaches of endurance exercise., Methods: Eighteen healthy volunteers (aged 24 ± 3 years) participated this three-arm, randomized-balanced crossover study. Each arm was a single bout of treadmill-based acute endurance exercise at (1) 100% of the individual anaerobic threshold (IANS), (2) at 80% of the IANS and (3) at 80% of the IANS with blood flow restriction (BFR). Load-associated outcomes (fatigue, feeling, heart rate, and exhaustion) as well as acute effects (circulating miRNA patterns and lactate) were determined., Results: All training interventions increased the lactate concentration (LC) and heart rate (HR) (p < 0.001). The high-intensity intervention (HI) resulted in a higher LC than both lower intensity protocols (p < 0.001). The low-intensity blood flow restriction (LI-BFR) protocol led to a higher HR and higher LC than the low-intensity (LI) protocol without BFR (p = 0.037 and p = 0.003). The level of miR-142-5p and miR-197-3p were up-regulated in both interventions without BFR (p < 0.05). After LI exercise, the expression of miR-342-3p was up-regulated (p = 0.038). In LI-BFR, the level of miR-342-3p and miR-424-5p was confirmed to be up-regulated (p < 0.05). Three miRNAs and LC show a significant negative correlation (miR-99a-5p, p = 0.011, r = - 0.343/miR-199a-3p, p = 0.045, r = - 0.274/miR-125b-5p, p = 0.026, r = - 0.302). Two partial correlations (intervention partialized) showed a systematic impact of the type of exercise (LI-BFR vs. HI) (miR-99a-59: r = - 0.280/miR-199a-3p: r = - 0.293)., Conclusion: MiRNA expression patterns differ according to type of activity. We concluded that not only the intensity of the exercise (LC) is decisive for the release of circulating miRNAs-as essential is the type of training and the oxygen supply., (© 2021. The Author(s).)

Plasma exosomes derived from healthy people have been shown to be beneficial in terms of protecting against ischemia-reperfusion injury or acute myocardial infarction (AMI). However, a pathological condition may severely affect the constitution and biological activity of exosomes. In our study, we isolated plasma exosomes from healthy volunteers and convalescent AMI patients (3-7 d after onset). Compared to exosomes from healthy controls (Nor-Exo), exosomes from convalescent AMI patients (AMI-Exo) exhibited an impaired ability to repair damaged cardiomyocytes both in vitro and in vivo. miRNA sequencing and PCR analysis indicated that miR-342-3p was significantly downregulated in AMI-Exo. Moreover, miR-342-3p alleviated H 2 O 2 -induced injury and reduced apoptosis and autophagy in H9c2 cardiomyocytes, while in vivo restoration of miR-342-3p expression enhanced the reparative function of AMI-Exo. Further mechanistic studies revealed that the SOX6 and TFEB genes were two direct and functional targets of miR-342-3p. Taken together, during the early convalescent phase after AMI, dysregulated miR-342-3p in plasma exosomes might be responsible for their impaired cardioprotective potential. miR-342-3p contributed to exosome-mediated heart repair by inhibiting cardiomyocyte apoptosis and autophagy through targeting SOX6 and TFEB, respectively. Our work provided novel insights on the role of plasma exosomes in the natural process of cardiac repair after AMI and suggestions for therapy development., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: The occurrence of chemoresistance is a common problem in tumor treatment. Circular RNA (circRNA) has been confirmed to be related to tumor chemoresistance. However, the role and the underlying molecular mechanism of hsa&#95;circ&#95;0004674 in the chemoresistance of osteosarcoma (OS) are still unclear., Methods: The expression of hsa&#95;circ&#95;0004674, miR-342-3p, and fibrillin-1 (FBN1) was determined by qRT-PCR. Cell counting kit 8 assay was used to evaluate the doxorubicin (DXR) resistance of cells. The proliferation and apoptosis of cells were measured using colony formation assay and flow cytometry. Western blot analysis was utilized to examine the protein levels of resistance markers, Wnt/β-catenin pathway markers and FBN1. The interaction between miR-342-3p and hsa&#95;circ&#95;0004674 or FBN1 was confirmed by dual-luciferase reporter assay and RNA pull-down assay. Moreover, animal experiments were performed to assess the effect of hsa&#95;circ&#95;0004674 silencing on the DXR sensitive of OS in vivo., Results: The upregulated hsa&#95;circ&#95;0004674 was found in DXR-resistant OS tissues and cells. Knockdown of hsa&#95;circ&#95;0004674 could inhibit the DXR resistance of OS cells in vitro and promote the DXR sensitive of OS tumors in vivo. In addition, we discovered that hsa&#95;circ&#95;0004674 could sponge miR-342-3p, and miR-342-3p could target FBN1. MiR-342-3p inhibitor could reverse the inhibition effect of hsa&#95;circ&#95;0004674 knockdown on the DXR resistance of OS cells. Similarly, the suppressive effect of miR-342-3p on the DXR resistance of OS cells also could be reversed by FBN1 overexpression. Furthermore, we revealed that hsa&#95;circ&#95;0004674 silencing inhibited the activity of Wnt/β-catenin pathway by the miR-342-3p/FBN1 axis., Conclusion: Hsa&#95;circ&#95;0004674 facilitated the DXR resistance of OS through Wnt/β-catenin pathway via regulating the miR-342-3p/FBN1 axis, suggesting that hsa&#95;circ&#95;0004674 was a promising target for the chemoresistance of OS., (© 2021. The Author(s).)

Background: Cancer-associated fibroblasts (CAFs) play a pivotal role in regulating tumor progression by transferring exosomes to adjacent cells. Our aim was to clarify the role of LINC00659 encapsulated in CAFs-derived exosomes (CAFs-exo) in colorectal cancer (CRC)., Methods: CAFs and normal fibroblasts (NFs) were isolated and cultured. CAFs-exo and NFs-derived exosomes (NFs-exo) were characterized by transmission electron microscope and Western blot. The mRNA level of LINC00659 in CAFs-exo and NFs-exo were measured. Then we analyzed cell proliferation by CCK-8 and clone formation assay, cell migration by cell scratch, and cell invasion by Transwell. Epithelial mesenchymal transformation (EMT) related markers E-cadherin, N-cadherin, Vimentin and Snail-1 expressions were assessed by Western blot. The binding of LINC00659 and miR-342-3p, miR-342-3p and ANXA2 were analyzed by dual-luciferase reporter gene assay., Results: CAFs and NFs showed a spindle-like morphology. CAFs-exo promoted CRC cell proliferation, migration, invasion and EMT progression. The expression of LINC00659 in CAF-derived exosomes was significantly increased, and fibroblasts could transfer exosomal LINC00659 to CRC cells. We further revealed that transfection of miR-342-3p mimic or sh-ANXA2 could obviously reverse the promotion effect of exosomal LINC00659 on CRC progression. Functional studies reveal that LINC00659 is transferred from CAFs to the cancer cells via exosomes, where it promotes CRC cell proliferation, invasion, migration and EMT progression in vitro. Mechanistically, LINC00659 interacts directly with miR-342-3p to increase ANXA2 expression in CRC cells., Conclusion: Collected evidence supported that CAFs-derived exosomal LINC00659 promotes CRC cell proliferation, invasion and migration via miR-342-3p/ANXA2axis.

Background: Long non-coding RNAs (lncRNAs) play important roles in the progression of tumors. However, the function and expression of SCARNA2 in cutaneous squamous cell carcinoma (cSCC) is still unreported., Methods: A quantitative polymerase chain reaction was applied to study the expression of SCARNA2 and miR-342-3p. Cell counting kit-8, flow cytometry and transwell assays were performed to study cell growth, cycle and cell invasion., Results: We found that SCARNA2 expression is up-regulated in cSCC cell lines and SCARNA2 expression is higher in cSCC tissues than in adjacent non-tumor specimens. Ectopic expression of SCARNA2 promoted cell growth, cell cycle and invasion in SCC13 cells. In addition, the data indicate that miR-342-3p expression is down-regulated in cSCC cell lines and miR-342-3p is down-regulated in cSCC tissues compared to adjacent non-tumor specimens. We showed that the SCARNA2 expression is negatively associated with miR-342-3p in cSCC. Moreover, we noted that SCARNA2 sponges miR-342-3p expression in cSCC cells. Overexpression of SCARNA2 suppressed the miR-342-3p expressed in SCC13 cells. We found that elevated expression of SCARNA2 promotes cell growth, cell cycle and invasion via regulating miR-342-3p expression in SCC13 cells., Conclusions: These data suggest that SCARNA2 acts in an oncogenic role and may be a potential target for cSCC., (© 2020 John Wiley & Sons, Ltd.)

Background: Radiotherapy is an effective strategy for preventing cancer metastasis, including osteosarcoma. However, cancer radioresistance limits the efficiency of radiotherapy. Therefore, it is essential to investigate the mechanism of osteosarcoma radioresistance., Methods: The osteosarcoma tissues and adjacent healthy tissues were collected from 53 osteosarcoma patients. The expression of LINC00210, miR-342-3p, and GFRA1 mRNA were determined using qRT-PCR. Cell viability, cell apoptosis, and cell surviving fraction were determined by MTT assay, flow cytometry, and colony formation assay, respectively. Western blot was performed to detect the protein levels. Luciferase assay was conducted to verify the relationship between LINC00210, miR-342-3p, and GFRA1., Results: LINC00210 and GFRA1 were up-regulated, and miR-342-3p was down-regulated in osteosarcoma tissues and cells. The expression of LINC00210 in osteosarcoma was negatively related to miR-342-3p expression and positively associated with GFRA1. Besides, there was a negative correlation between LINC00210 and GFRA1 expression in osteosarcoma. Also, LINC00210 and GFRA1 were up-regulated, and miR-342-3p was down-regulated in osteosarcoma cells exposed to 4 Gy irradiation treatment. Furthermore, either LINC00210 knockdown or miR-342-3p overexpression enhanced the radiosensitivity of osteosarcoma cells. Moreover, LINC00210 increased GFRA1 expression via sponging miR-342-3p. Additionally, LINC00210 knockdown improved the radiosensitivity of osteosarcoma cells by regulating GFRA1 expression via sponging miR-342-3p., Conclusion: LINC00210 modulated the radiosensitivity of osteosarcoma cells via the miR-342-3p/GFRA1 axis, making LINC00210 a novel target for improving radiotherapy efficiency in osteosarcoma., (© 2020 The Authors. Journal of Clinical Laboratory Analysis Published by Wiley Periodicals LLC.)

Background: Prostate cancer (PCa) is the second most common cancer among men, threatening men's health and life. Long noncoding RNA Zinc-finger E-box binding homeobox 1 antisense gene 1 (ZEB1-AS1) and Cullin 4B (CUL4B) were reported to be connected with the tumorigenesis of PCa. However, it is unclear whether ZEB1-AS1 regulates the expression of CUL4B in PCa. Materials and Methods: The levels of ZEB1-AS1 and CUL4B in PCa tissues and cells were evaluated by quantitative real-time polymerase chain reaction. Protein levels of CUL4B, p21, CyclinD1, matrix metalloprotease 9 (MMP9), E-cadherin, phosphorylated-phosphatidylinositol 3 kinase (p-PI3K), PI3K phosphorylated protein kinase B (p-AKT), AKT, p-mTOR and mammalian target of rapamycin (mTOR) in PCa tissues or cells were assessed by Western blot analysis. The proliferation, migration, and invasion abilities of PCa cells were determined with 3-(4, 5-dimethylthiazol-2-YI)-2,5-diphenyltetrazolium bromide (MTT) or transwell assay. The interaction between ZEB1-AS1 or CUL4B and microRNA-342-3p (miR-342-3p) was predicted using starBase v2.0 database and confirmed by the dual-luciferase reporter assay. Results: ZEB1-AS1 and CUL4B were upregulated and miR-342-3p was downregulated in PCa tissues and cells. Both ZEB1-AS1 and CUL4B inhibition constrained proliferation, migration, and invasion of PCa cells. Moreover, the elevation of CUL4B reversed the effects of ZEB1-AS1 silencing on the proliferation, migration, and invasion of PCa cells. Importantly, ZEB1-AS1 modulated CUL4B expression by sponging miR-342-3p in PCa cells. Besides, ZEB1-AS1 mediated PI3K/AKT/mTOR signal pathway by miR-342-3p/CUL4B axis in PCa cells. Conclusion: ZEB1-AS1 modulated PCa progression through mediating PI3K/AKT/mTOR signaling by miR-342-3p/CUL4B axis, providing a possible strategy for the treatment of PCa.

Background: miR-342-3p, localized to 14q32, is a tumor suppressor miRNA implicated in carcinogenesis. Given the presence of a promotor-associated CpG island for its host gene, EVL, we hypothesized that intronic miR-342-3p is a tumor suppressor co-regulated with host gene by promoter DNA methylation in B cell lymphoma., Results: By bisulfite pyrosequencing-verified methylation-specific PCR (MSP), EVL/MIR342 methylation was detected in five (50%) lymphoma cell lines but not normal peripheral blood and tonsils. EVL/MIR342 methylation correlated with repression of both miR-342-3p and EVL in cell lines. In completely methylated SU-DHL-16 cells, 5-AzadC treatment resulted in promoter demethylation and re-expression of miR-342-3p and EVL. In 132 primary lymphoma samples, EVL/MIR342 was preferentially methylated in B cell lymphomas (N = 68; 68.7%) than T cell lymphoma (N = 8; 24.2%) by MSP (P < 0.0001). Moreover, EVL/MIR342 methylation was associated with lower miR-342-3p expression in 79 primary NHL (P = 0.0443). In SU-DHL-16 cells, the tumor suppressor function of miR-342-3p was demonstrated by the inhibition of cellular proliferation and increase of cell death upon over-expression of miR-342-3p. Mechanistically, overexpression of miR-342-3p resulted in a decrease of LC3-II, a biomarker of autophagy, which was pro-survival for SU-DHL-16. Pre-treatment with 3-methyladenine, an autophagy inhibitor, abrogated tumor suppression associated with miR-342-3p overexpression. By luciferase assay, MAP1LC3B, a precursor of LC3-II, was confirmed as a direct target of miR-342-3p. Finally, in SU-DHL-16 cells, overexpression of miR-342-3p downregulated the known target DNMT1, with promoter demethylation and re-expression of tumor suppressor E-cadherin., Conclusions: Intronic miR-342-3p is co-regulated with its host gene EVL by tumor-specific promoter DNA methylation in B cell lymphoma. The tumor suppressor function of miR-342-3p was mediated via inhibition of pro-survival autophagy by targeting MAP1LC3B and downregulation of DNMT1 with demethylation and re-expression of tumor suppressor genes.

Abdominal aortic aneurysm (AAA) is fatal meanwhile unpredictable asymptomatic cardiovascular disease. Available data suggests the potential participation of circular RNAs (circRNAs) in AAA pathogenesis. But direct evidence is limited. The present study is to functionally and mechanically characterize circRNA CCDC66 (circCCDC66) in AAA. Previous work indicated the differentially expressed circCCDC66 in AAA. At molecular level, circCCDC66, miR-342-3p and CCDC66 transcript were measured through real-time quantitative polymerase chain reaction assay. Functionally, we examined the cellular behaviours of circCCDC66-depleted or CCDC66-depleted vascular smooth muscle cells (VSMCs) including proliferation and apoptosis. It elucidated that depletion of circCCDC66 induced proliferation facilitation and apoptosis reduction. Mechanically, we addressed the interplay among circCCDC66, miR-342-3p and CCDC66 transcript using RNA immunoprecipitation, RNA pull-down and luciferase reporter experiments. Through mechanical validation, we discovered the positive regulation of circCCDC66 on its host gene CCDC66. Loss of CCDC66 mimicked the effects of circCCDC66 silencing on VSMC growth. Moreover, it uncovered that circCCDC66 regulated CCDC66-dependent VSMC growth through sponging miR-342-3p. Rescue experiments aimed to address the functional role of regulatory network formed by circCCDC66, miR-342-3p and CCDC66 in VSMC growth and apoptosis. Suppressing miR-342-3p or overexpressing CCDC66 could reverse VSMC growth caused by circCCDC66 deficiency. Our study further emphasized and first unveiled the function of circCCDC66 in VSMC proliferation. CircCCDC66 upregulated its host gene through its role of miR-342-3p sponge, and hinted a novel molecular mechanism in AAA. SIGNIFICANCE OF THE STUDY: It was firstly displayed in our study that depletion of circCCDC66 induced proliferation augmentation and apoptosis reduction of vascular smooth muscle cells (VSMCs). Meanwhile, circCCDC66/miR-342-3p/CCDC66 axis was proved can play the function of modulating the cell proliferation and apoptosis of VSMCs, which provided us a novel molecular mechanism in AAA., (© 2020 John Wiley & Sons Ltd.)

Background: Non-small cell lung cancer (NSCLC) is one of the major types of lung cancer, which is a prevalent human disease all over the world. LncRNA LINC01503 is a super-enhancer-driven long non-coding RNA that is dysregulated in several types of human cancer. However, its role in NSCLC remains unknown., Methods: Thirty NSCLC patients were recruited between April 2012 and April 2016. Luciferase reporter assay, qRT-PCR, Cell Counting Kit-8 (CCK-8), Transwell migration assay, RNA pull-down assay, western blotting, 5-ethynyl-29-deoxyuridine (EdU) assays, and flow cytometry were utilized to characterize the roles and relationships among LINC01503, miR-342-3p, and LASP1 in NSCLC. The transplanted mouse model was built to examine their biological functions in vivo., Results: We demonstrated that the expression of lncRNA LINC01503 and LIM and SH3 domain protein 1 (LASP1) were upregulated and miR-342-3p was downregulated in NSCLC samples and cell lines. Functional experiments revealed that inhibiting the expression of LINC01503 or over-expression of miR-342-3p inhibited NSCLC growth and metastasis both in vitro and in vivo. In addition, LINC01503 could bind to miR-342-3p and affect the expression of LASP1., Conclusion: These results provide a comprehensive analysis of the roles of LINC01503 as a competing endogenous RNA (ceRNA) in NSCLC progression.

Background: Glioma is the most common and lethal primary brain tumor in adults, and angiogenesis is one of the key factors contributing to its proliferation, aggressiveness, and malignant transformation. However, the discovery of novel oncogenes and the study of its molecular regulating mechanism based on circular RNAs (circRNAs) may provide a promising treatment target in glioma., Methods: Bioinformatics analysis, qPCR, western blotting, and immunohistochemistry were used to detect the expression levels of ISL2, miR-342-3p, circRNA ARF1 (cARF1), U2AF2, and VEGFA. Patient-derived glioma stem cells (GSCs) were established for the molecular experiments. Lentiviral-based infection was used to regulate the expression of these molecules in GSCs. The MTS, EDU, Transwell, and tube formation assays were used to detect the proliferation, invasion, and angiogenesis of human brain microvessel endothelial cells (hBMECs). RNA-binding protein immunoprecipitation, RNA pull-down, dual-luciferase reporter, and chromatin immunoprecipitation assays were used to detect the direct regulation mechanisms among these molecules., Results: We first identified a novel transcription factor related to neural development. ISL2 was overexpressed in glioma and correlated with poor patient survival. ISL2 transcriptionally regulated VEGFA expression in GSCs and promoted the proliferation, invasion, and angiogenesis of hBMECs via VEGFA-mediated ERK signaling. Regarding its mechanism of action, cARF1 upregulated ISL2 expression in GSCs via miR-342-3p sponging. Furthermore, U2AF2 bound to and promoted the stability and expression of cARF1, while ISL2 induced the expression of U2AF2, which formed a feedback loop in GSCs. We also showed that both U2AF2 and cARF1 had an oncogenic effect, were overexpressed in glioma, and correlated with poor patient survival., Conclusions: Our study identified a novel feedback loop among U2AF2, cARF1, miR-342-3p, and ISL2 in GSCs. This feedback loop promoted glioma angiogenesis, and could provide an effective biomarker for glioma diagnosis and prognostic evaluation, as well as possibly being used for targeted therapy.

The aim of this paper was to investigate the effect of flavonoids of Sophorae Fructus on the proliferation, migration and invasion of hepatocellular carcinoma cells and analyze the regulatory mechanism of LncRNA FBXL19-AS1/miR-342-3 p pathway. MTT assay and plate cloning assay were used to detect the effect of flavonoids of Sophorae Fructus at different concentrations(1, 5, 10 mg·mL~(-1)) on the proliferation of liver cancer Huh7 cells. The effect of flavonoids of Sophorae Fructus on the migration and invasion of Huh7 cells was examined by Transwell chamber assay. qRT-PCR was used to detect the effect of flavonoids of Sophorae Fructus on the expression levels of FBXL19-AS1 and miR-342-3 p in Huh7 cells. The dual luciferase reporter assay was used to detect whether FBXL19-AS1 targeted at miR-342-3 p. The effect on the inhibition of FBXL19-AS1 expression or FBXL19-AS1 overexpression and then the proliferation, migration and invasion of Huh7 cells were examined by the above methods. Gelatin zymography was used to detect the activities of MMP-2 and MMP-9. The expression levels of cyclinD1, p21, MMP-2 and MMP-9 proteins were detected by Western blot. Flavonoids of Sophorae Fructus significantly inhibited the proliferation, migration and invasion of Huh7 cells(P&lt;0.05), promoted the expression of p21 protein(P&lt;0.05), and inhibited the expressions of cyclinD1, MMP-2 and MMP-9(P&lt;0.05) in a dose-dependent manner, and could reduce the activity of MMP-2 and MMP-9(P&lt;0.05). The expression level of FBXL19-AS1 was significantly decreased in Huh7 cells treated with flavonoids of Sophorae Fructus(P&lt;0.05), whereas the expression level of miR-342-3 p was significantly increased(P&lt;0.05). The dual luciferase reporter assay confirmed that FBXL19-AS1 targeted at the inhibition of miR-342-3 p expression. After inhibiting the expression of FBXL19-AS1, the inhibition rate of cell proliferation was significantly increased(P&lt;0.05), the number of cell clone formation was significantly reduced(P&lt;0.05), the number of migrated cells and the number of invasive cells were significantly decreased(P&lt;0.05), and the expression levels of cyclinD1, MMP-2 and MMP-9 were significantly decreased(P&lt;0.05), the activities of MMP-2 and MMP-9 were significantly reduced(P&lt;0.05), while the expression level of p21 protein was significantly increased(P&lt;0.05). The overexpression of FBXL19-AS1 reversed the inhibitory effect of flavonoids of Sophorae Fructus on the proliferation, migration and invasion of Huh7 cells. Flavonoids of Sophorae Fructus could inhibite the proliferation, migration and invasion of hepatoma cells by regulating LncRNA FBXL19-AS1/miR-342-3 p pathway.

Cervical cancer (CC), an aggressive malignancy, has a high risk of relapse and death, mainly occurring in females. Accumulating investigations have confirmed the critical role of long noncoding RNAs (lncRNAs) in diverse cancers. LncRNA LINC01503 has been reported as an oncogene in several cancers. Nonetheless, its role and molecular mechanism in CC have not been explored. In the present study, we found that FXYD3 expression was considerably up-regulated in CC tissues and cells. Moreover, FXYD3 deficiency conspicuously hampered cell proliferation and migration while facilitated cell apoptosis in CC cells. Subsequently, molecular mechanism experiments implied that FXYD3 was a downstream target gene of miR-342-3p, and FXYD3 expression was reversely mediated by miR-342-3p. Moreover, we discovered that LINC01503 acted as the endogenous sponge for miR-342-3p. Besides, LINC01503 negatively regulated miR-342-3p expression and positively regulated FXYD3 expression in CC. Rescue assays revealed that LINC01503 depletion-induced repression on CC progression could be partly recovered by miR-342-3p inhibition, and then the co-transfection of sh-FXYD3#1 rescued this effect. Conclusively, LINC01503 aggravated CC progression through sponging miR-342-3p to mediate FXYD3 expression, providing promising therapeutic targets for CC patients., (© 2020 The Author(s).)

Hepatocellular carcinoma (HCC) is the fifth most common malignant tumor in the world. It ranks third among cancer-induced deaths worldwide and has the characteristics of high metastasis and high recurrence rate. Long non-coding RNA (LncRNA) LINC00460 is significantly up-regulated in multiple types of cancers and is closely related to the progression of tumors. However, effects of LINC00460 and corresponding regulatory path in HCC are still poorly investigated.In our study, we found that expression of LINC00460 was up-regulated in HCC tissues and cell lines compared with the control. Then we revealed that knockdown of LINC00460 suppressed cell proliferation and cell mobility and induced cell apoptosis in HCC cells. Further study demonstrated that knockdown of LINC00460 suppressed the progression of HCC by elevating the expression of microRNA (miRNA, miR)-342-3p. Besides that, metastasis marker, Anterior gradient homolog 2 (AGR2) was found to be a target of miR-342-3p and overexpression of AGR2 promoted the progression of HCC. Finally, the in vivo experiments further verified the anti-tumor effects of LINC00460 / miR-342-3p / AGR2 axis in HCC.The LINC00460 / miR-342-3p / AGR2 axis exerts anti-tumor effect in HCC in vitro and in vivo , consolidating and expanding the research about targeted gene therapy for early diagnosis and treatment of HCC.

Opa-interacting protein 5 antisense RNA 1 (OIP5-AS1), a long non-coding RNA (lncRNA), has been reported to link with the progression of some cancers. However, its biological functions and underlying molecular mechanisms in pancreatic cancer are largely unknown. The aim of this study was to investigate the role of lncRNA OIP5-AS1 in pancreatic cancer. Quantitative real-time PCR analysis revealed that OIP5-AS1 is highly expressed in pancreatic cancer tissues versus adjacent non-tumor tissues. In vitro functional assays showed that downregulation of OIP5-AS1 or overexpression of miR-342-3p inhibited the proliferation, decreased Ki67 expression, and induced cell cycle arrest in pancreatic cancer cells. The expression of cyclinD1, CDK4, and CDK6 was decreased by knockdown of OIP5-AS1. Moreover, we found that OIP5-AS1 acted as a miR-342-3p sponge to suppress its expression and function. Dual-luciferase assay confirmed the interaction of OIP5-AS1 and miR-342-3p and verified anterior gradient 2 (AGR2) as a direct target of miR-342-3p. Results showed that depletion of miR-342-3p abolished the inhibitory effects of OIP5-AS1 knockdown on pancreatic cancer cell growth. The expression of Ki67, AGR2, cyclinD1, CDK4, CDK6, p-AKT, and p-ERK1/2 was reversed by silencing of miR-342-3p in pancreatic cancer cells with OIP5-AS1 knockdown. Further, knockdown of OIP5-AS1 suppressed tumor growth in a xenograft mouse model of pancreatic cancer. OIP5-AS1 induced pancreatic cancer progression via activation of AKT and ERK signaling pathways. Therefore, we demonstrate that OIP5-AS1 functions as oncogene in pancreatic cancer and its downregulation inhibits pancreatic cancer growth by sponging miR-342-3p via targeting AGR2 through inhibiting AKT/ERK signaling pathway.

Purpose: Osteosarcoma (OS) is the most common primary bone tumor, with high morbidity in infants and adolescents. Long noncoding RNA LINC00313 has been found to modulate papillary thyroid cancer tumorigenesis and to be dysregulate in lung cancer. However, the role of LINC00313 in OS has not yet been addressed., Materials and Methods: We evaluated mRNA and protein expression using real-time quantitative PCR and Western blotting. Cell proliferation was evaluated using MTT; apoptosis and autophagy were assessed with flow cytometry, Western blotting, and/or GFP-LC3 assay. Transwell assay was conducted to measure cell migration and invasion. Potential target sites for LINC00313 and miR-342-3p were predicted with starBase v.2.0 and TargetScan Human, and verified using luciferase reporter assay, RNA immunoprecipitation, and RNA pull-down assay. In vivo, xenogeneic tumors were induced with U2OS and MG-63 cells, separately., Results: LINC00313 was upregulated and miR-342-3p was downregulated in OS tissues and cells. High expression of LINC00313 was associated with shorter overall survival. FOSL2 downregulation and miR-342-3p overexpression suppressed cell proliferation and migratory and invasive abilities while promoting apoptosis and autophagy, all of which were consistent with the effects of LINC00313 knockdown. miR-342-3p, sponged by LINC00313, inversely modulated FOSL2 by targeting MG-63 cells, and FOSL2 expression was positively controlled by LINC00313. LINC00313 knockdown suppressed tumor growth in vivo., Conclusion: LINC00313 is upregulated in OS, and LINC00313 knockdown plays a vital anti-tumor role in OS cell progression through a miR-342-3p/FOSL2 axis. Our study suggests that LINC00313 may be a novel, promising biomarker for diagnosis and prognosis of OS., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2020.)

Pancreatic ductal adenocarcinoma (PDAC) is one of the most invasive solid tumours and has the highest cancer-related mortality rate. Despite intense investigation, the molecular mechanisms underlying the invasiveness and aetiology of PDAC remain elusive. MicroRNAs (miRNAs) are key regulators of tumour cell plasticity, but their roles in PDAC metastasis have not been characterized. Our early studies showed that dysbindin protein levels are elevated in PDAC patients compared with control individuals and that dysbindin upregulation elicits PDAC cell proliferation via the PI3K pathway. Here, we show that dysbindin promoted PDAC metastasis via the NF-κB/MDM2 signalling axis. Increased dysbindin levels correlated with aggressive features in PDAC, and the overexpression of dysbindin significantly promoted PDAC metastasis and invasion in vitro and in vivo. Surprisingly, dysbindin was identified as a direct target of miR-342-3p, which promotes NF-κB activation and PDAC metastasis. Thus, dysbindin-mediated NF-κB activation via miR-342-3p represents a context-dependent switch that enables PDAC cell proliferation and metastasis. Our data suggest that dysbindin and miR-342-3p are potential leads for the development of targeted therapy for PDAC., Competing Interests: Declaration of competing interest The authors have declared that no conflict interests exist., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Hepatocellular carcinoma (HCC) is the leading cause of cancer-related death worldwide. LINC00460, a novel long non-coding RNA (lncRNA), was recently confirmed as an oncogene in various cancers. However, the biological function and underlying mechanism of LINC00460 in HCC is largely obscure., Methods: Fifty pairs of tumor tissue and adjacent normal tissues from HCC patients, as well as six HCC cell lines and a normal human hepatic epithelial cell line were subjected to qRT-PCR assay to evaluate the expression levels of LINC00460. CCK-8 assays were used to detect the proliferation of HCC cells. Transwell assay was used to measure the migration and invasion abilities of HCC cells. RNA pull-down and luciferase assays were performed to verify the direct interaction between LINC00460 and miR-342-3p. A xenograft model of HCC was established to validate the in vivo function of LINC00460 in HCC progression., Results: We firstly detected LINC00460 expression was significantly upregulated in both HCC tumor tissues and cell lines. The upregulation of LINC00460 was positively associated with HCC progression. Functionally, LINC00460 facilitated HCC cell proliferation, migration, and invasion capacities, which due to that LINC00460 could physically bind to and repress miR-342-3p to elevate the expression of AGR2., Conclusion: Our data firstly reveal the clinical relevance, biological function, and regulatory mechanism of LINC00460 in HCC development. LINC00460 promotes HCC progression by elevating AGR2 expression via sponging miR-342-3p, providing a promising therapeutic target for HCC treatment., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Yang et al.)

Background: Aberrant expression of long non-coding RNAs (lncRNAs) is closely associated with development and prognosis of human cancers. LncRNA SNHG16 is reportedly involved in human cancer; however, its roles in multiple myeloma (MM) remain unclear., Methods: In this study, we investigated the function and molecular mechanisms of SNHG16 in MM. MM cells were transfected with si-SNHG16 or si-NC. SNHG16 expression levels was measured by qRT-PCR. Cell proliferation was monitored using the MTS. Flow cytometry assay was performed to measure the cell cycle and apoptosis. Luciferase reporter assay were performed to confirm the sponged miRNAs of SNHG16., Results: SNHG16 expression was up-regulated in MM tissues. SNHG16 knockdown suppressed cell proliferation, arrested cell cycle transition from G1 to S phase, and promoted the apoptosis of MM cells. Moreover, SNHG16 knockdown promoted cleaved-Caspase-3, cleaved-Caspase-9, Foxa3a, and Bax expression, while markedly inhibiting CCND1 , Bcl-2, Cyclin D1, PI3K, and p-AKT expression in MM cells. miR-342-3p was a direct target of SNHG16. SNHG16 knockdown significantly increased miR-342-3p expression in MM cells. Overexpression miR-342-3p markedly suppressed cell proliferation, arrested cell cycle transition from G1 to S phase, and promoted apoptosis of MM cells. Overexpression of miR-342-3p markedly promoted cleaved-Caspase-3/-9, Foxa3a, and Bax expression, and inhibited CCND1 , Bcl-2, Cyclin D1, PI3K, and p-AKT expression in MM cells. Additionally, repression of miR-342-3p could rescue the effect of SNHG16 knockdown on MM cell proliferation, cycle arrest, apoptosis, and related protein expression., Conclusion: Knockdown of lncRNA SNHG16 suppresses MM cell proliferation by sponging miR-342-3p, implicating SNHG16 as a novel therapeutic target for MM., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2020.)

Aim: This study aimed to explore the miR-342-3p expression in pre-eclampsia (PE) placentas and confirm whether miR-342-3p exerts effects on proliferation and migration of HTR-8/SVneo trophoblastic cells., Methods: The PE placentas (n = 8) were taken from gravidas complicated by PE and delivered after 34 weeks. The chorionic plates and the basal plates were separately taken from the placenta disc near the position of umbilical cord insertion. RT-qPCR was used to measure the expression of miR-342-3p in the chorionic plates and the basal plates. Cell invasion assay and MMT assay were used to assess the effects of miR-342-3p on proliferation and migration of HTR-8/SVneo trophoblastic cells. Luciferase reporter assay and Western blotting were used to analyze the target of miR-342-3p and investigate the detailed mechanisms., Results: The expression of miR-342-3p was upregulated in both basal plates and chorionic plates in patients with PE compared with healthy pregnant individuals. MiR-342-3p inhibitor suppressed the cell viability and invasion, and induced apoptosis in trophoblast cells. Furthermore, inhibitor of DNA binding (ID)-4 (ID4) was a direct target of miR-342-3p, and knockdown of ID4 abrogated the regulation effect of miR-342-3p on cell viability, apoptosis and invasion., Conclusion: Inhibition of miR-342-3p expression may suppress the occurrence of PE by targeting ID4 in vitro., (© 2019 Japan Society of Obstetrics and Gynecology.)

Many long noncoding RNAs reportedly have tumor suppressive roles or are oncogenic in esophageal cancer. We have previously performed a chip-based expression analysis of primary esophageal cancer tissues and found that the expression of LINC00634 in these tissues was higher than that in nontumor tissues. Quantitative real-time-polymerase chain reaction, cell counting kit-8, flow cytometry, caspase3/7 assay, dual-luciferase reporter assay, and restore assay were used to detect the proliferative and apoptotic effects of LINC00634 in esophageal cancer cells. The results showed that the expression of LINC00634 in these tissues was higher than that in nontumor tissues and associated with tumor-node-metastasis (TNM) stage of patients. Knockdown of LINC00634 decreased cell viability and increased cell apoptosis levels in EC9706 and EC1 cells. LINC00634 could target Bcl2L1 through miR-342-3p. In this study, we show that LINC00634 is upregulated in esophageal cancer. We also show that the knockdown of LINC00634 decreased cell viability and increased cell apoptosis levels in EC9706 and EC1 cells through the miR-342-3p/Bcl2L1 axis.

Background: Non-small cell lung cancer (NSCLC) accounts for about 80-85% of lung cancers. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) such as gefitinib are considered the best choice for first-line treatment for the patients with NSCLC harboring EGFR-activating alterations. Nonetheless, 10-30% of patients may not obtain an objective response and may also experience rapid progression. The aim of our research, based on the integrative bioinformatics review, was to identify the possible miRNAs involved in gefitinib resistance., Method: A gefitinib-resistant network composed of 15 miRNAs and 34 targets were constructed by using the bioinformatics analyses of three microarray datasets. Of these miRNAs, effects of miR-342-3p on gefitinib resistance were investigated on a gefitinib-resistant cell model (A549/GR and PC/GR cells)., Results: We reported that over-expression of miR-342-3p could significantly increase the resistance to gefitinib of A549/GR and PC9/GR cells and vice versa. Then, we recognized CPA4 as a target of hsa-miR-342-3p by a luciferase reporter assay. The increase in hsa-miR-342-3p levels led to a significant reduction in CPA4 protein expression. However, the opposite results were observed upon miR-342-3p knockdown. Finally, we found that enforced CPA4 expression partially reversed miR-342-3p effects in A549/GR cells., Conclusions: Collectively, these findings suggest that the upregulation of miR-342-3p contributes to gefitinib resistance by targeting CPA4, which may serve as a potential treatment option to overcome gefitinib resistance in patients with NSCLC., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (2019 Journal of Thoracic Disease. All rights reserved.)

Objective: To investigate the mechanism of LncRNA H19 in Th17 cell differentiation and endometrial stromal cells (ESCs) proliferation in endometriosis (EMS)., Methods: LncRNA H19, miR-342-3p and IER3 expressions were detected by qRT-PCR and western blot. The percentage of Th17 cells/CD4+ T cells was detected by flow cytometry. IL-17 level was measured by ELISA. The interaction of miR-342-3p and IER3 was confirmed by Luciferase reporter assay., Results: LncRNA H19 and IER3 expressions were down-regulated in mononuclear cells from peritoneal fluid (PFMCs) of patients with EMS or under Th17 differentiation conditions, whereas miR-342-3p expression was up-regulated and the percentage of Th17 cells was increased in PFMCs of patients with EMS or under Th17 differentiation conditions. Over-expression of LncRNA H19 decreased IL-17 level and the percentage of Th17 cells/CD4+ T cells. Besides, we confirmed that miR-342-3p could target to IER3 and negatively regulate IER3 expression. LncRNA H19 over-expression suppressed Th17 differentiation and ESC proliferation through regulating miR-342-3p/IER3. In vivo experiments showed LncRNA H19 over-expression suppressed the growth of Th17 cell differentiation-induced endometriosis-like lesions., Conclusion: LncRNA H19 was down-regulated in PFMC of patients with EMS or under Th17 polarizing conditions, and LncRNA H19 over-expression suppressed Th17 cell differentiation and ESCs proliferation through miR-342-3p/IER3 pathway., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2019.)

Atherosclerosis has been recognized as a chronic inflammation process induced by lipid of the vessel wall. Oxidized low-density lipoprotein (ox-LDL) can drive atherosclerosis progression involving macrophages. Recently, long noncoding RNAs (lncRNAs) have been reported to play critical roles in atherosclerosis development. In our current study, we focused on the biological roles of lncRNA NEAT1 in atherosclerosis progress. Here, we found that ox-LDL was able to trigger human macrophages THP-1 cells, a human monocytic cell line, apoptosis in a dose-dependent and time-dependent course. In addition, we observed that NEAT1 was significantly increased in THP-1 cells incubated with ox-LDL and meanwhile miR-342-3p was greatly decreased. Then, NEAT1 was silenced by transfection of small interfering RNA (siRNA) of NEAT1 into THP-1 cells. As exhibited, CD36, oil-red staining levels, total cholesterol (TC), total cholesterol (TG) levels and THP-1 cell apoptosis were obviously repressed by knockdown of NEAT1. Furthermore, inhibition of NEAT1 contributed to the repression of inflammation in vitro. Interleukin 6 (IL-6), IL-1β, cyclooxygenase-2 (COX-2) and tumour necrosis factor-alpha (TNF-α) protein levels were remarkably depressed by NEAT1 siRNA in THP-1 cells. By using bioinformatics analysis, miR-342-3p was predicted as a downstream target of NEAT1 and the correlation between them was confirmed in our study. Moreover, overexpression of miR-342-3p could also greatly suppress inflammation response and lipid uptake in THP-1 cells. Knockdown of NEAT1 and miR-342-3p mimics inhibited lipid uptake in THP-1 cells. In conclusion, we implied that blockade of NEAT1 repressed inflammation response through modulating miR-342-3p in human macrophages THP-1 cells and NEAT1 may offer a promising strategy to treat atherosclerotic cardiovascular diseases., (© 2018 Wiley Periodicals, Inc.)

Background: Small nucleolar RNA host gene 7 (SNHG7) is a novel identified oncogenic gene in tumorigenesis. However, the role that SNHG7 plays in pancreatic cancer (PC) remains unclear. In this study, we aimed to investigate the functional effects of SNHG7 on PC and the possible mechanism., Methods: The expression levels of SNHG7 in tissues and cell lines were measured by RT-qPCR. Cell viability, apoptosis, migration and invasion were examined to explore the function of SNHG7 on PC. Bioinformatics methods were used to predict the target genes. The mechanism was further investigated by transfection with specific si-RNA, miRNA mimics or miRNA inhibitor. Tumor xenograft was carried out to verify the effects of SNHG7 in vivo., Results: We found that SNHG7 was overexpressed in both PC tissues and cell lines. High expression level of SNHG7 was correlated with the poor prognosis. SNHG7 knockdown inhibited the proliferation, migration and invasion of PC cells. Moreover, SNHG7 was found to regulate the expression of ID4 via sponging miR-342-3p. Additionally, this finding was supported by in vivo experiments., Conclusions: LncRNA SNHG7 was overexpressed in PC tissues, and knockdown of SNHG7 suppressed PC cell proliferation, migration and invasion via miR-342-3p/ID4 axis. The results indicated that SNHG7 as a potential target for clinical treatment of PC., Competing Interests: The authors declare that they have no competing interests.