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Ovarian cancer (OC) is among the most common and deadly solid malignancies in women. Despite many advances in OC research, the incidence of OC continues to rise, and its pathogenesis remains largely unknown. Herein, we elucidated the function of hsa_circ_0061179 in OC. The levels of hsa_circ_0061179, miR-143-3p, TIMELESS, and DNA damage repair-related proteins in OC or normal ovarian tissues and cells were measured using real-time quantitative polymerase chain reaction and immunoblotting. The biological effects of hsa_circ_0061179 and miR-143-3p on proliferation, clone formation, DNA damage, and apoptosis of OC cells were detected by the cell counting kit-8 assay, 5-methylethyl-2'-deoxyuridine, flow cytometry, the comet assay, and immunofluorescence staining combined with the confocal microscopy. The interaction among hsa_circ_0061179, miR-143-3p, and TIMELESS was validated by the luciferase reporter assay. Mice tumor xenograft models were used to evaluate the influence of hsa_circ_0061179 on OC growth in vivo. We found that human OC biospecimens expressed higher levels of hsa_circ_0061179 and lower levels of miR-143-3p. Hsa_circ_0061179 was found to bind with miR-143-3p, which directly targets TIMELESS. Hsa_circ_0061179 knockdown or miR-143-3p overexpression suppressed the proliferation and clone formation of OC cells and increased DNA damage and apoptosis of OC cells via the miR-143-3p/TIMELESS axis. Furthermore, we demonstrated that METTL3 could direct the formation of has_circ_0061179 through a specific m6A modification site. YTHDC1 facilitated the cytoplasmic transfer of has_circ_0061179 by directly binding to the modified m6A site. Our findings suggest that hsa_circ_0061179 acts as the sponge of miR-143-3p to activate TIMELESS signaling and inhibits DNA damage and apoptosis in OC cells., (© 2024 The Authors. Molecular Carcinogenesis published by Wiley Periodicals LLC.)

Porcine circovirus type 2 (PCV2) infection leads to multi-system inflammation in pigs, and this effect can be achieved by upregulating host miR-21. The underlying mechanism of miR-21 regulates PCV2-induced inflammation is already known, however, how PCV2 regulates miR-21 levels and function using both autonomic and host factors remains to be further revealed. Here we present the first evidence that PCV2 ORF5 induces an inflammatory response by up-regulating miR-21 level through targeting nuclear miR-30d. In this study, we found that overexpression of ORF5 significantly increased miR-21 level and promoted the expression of inflammatory cytokines and activation of the NF-κB pathway, while ORF5 mutation had the opposite effect. Moreover, the differential expression of miR-21 could significantly change the pro-inflammatory effect of ORF5, indicating that ORF5 promotes inflammatory response by up-regulating miR-21. Bioinformatics analysis and clinical detection found that nuclear miR-30d was significantly down-regulated after ORF5 overexpression and PCV2 infection, and targeted pri-miR-21 and PCV2 ORF5. Functionally, we found that miR-30d inhibited the levels of miR-21 and inflammatory cytokines in cells. Mechanistically, we demonstrated that ORF5 inhibits miR-30d expression levels through direct binding but not via the circRNA pathway, and miR-30d inhibits miR-21 levels by targeting pri-miR-21. In summary, the present study revealed the molecular mechanism of ORF5 upregulation of miR-21, further refined the molecular chain of PCV2-induced inflammatory response and elucidated the role of miRNAs in it., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Purpose: It is well acknowledged that tobacco-derived lung carcinogens can induce lung injury and even lung cancer through a complex mechanism. MicroRNAs (MiRNAs) are differentially expressed in tobacco-derived carcinogen nicotine-derived nitrosamine ketone (NNK)-treated A/J mice., Experimental Approach: RNA sequencing was used to detect the level of long non-coding RNAs (lncRNAs). Murine and human lung normal and cancer cells were used to evaluate the function of lncRNA XIST and miR-328-3p in vitro, and NNK-treated A/J mice were used to test their function in vivo. In vivo levels of miR-328-3p and lncRNA XIST were analysed, using in situ hybridization. miR-328-3p agomir and lncRNA XIST-specific siRNA were used to manipulate in vivo levels of miR-328-3p and lncRNA XIST in A/J mice., Key Results: LncRNA XIST was up-regulated in NNK-induced lung injury and dominated the NNK-induced ectopic miRNA expression in NNK-induced lung injury both in vitro and in vivo. Either lncRNA XIST silencing or miR-328-3p overexpression exerted opposing effects in lung normal and cancer cells regarding cell migration. LncRNA XIST down-regulated miR-328-3p levels as a miRNA sponge, and miR-328-3p targeted the 3'-UTR of FZD 7 mRNA, which is ectopically overexpressed in lung cancer patients. Both in vivo lncRNA XIST silencing and miR-328 overexpression could rescue NNK-induced lung injury and aberrant overexpression of the lung cancer biomarker CK19 in NNK-treated A/J mice., Conclusions and Implications: Our results highlight the promotive effect of lncRNA XIST in NNK-induced lung injury and elucidate its post-transcriptional mechanisms, indicating that targeting lncRNA XIST/miR-328-3p could be a potential therapeutic strategy to prevent tobacco carcinogen-induced lung injury in vivo., (© 2024 British Pharmacological Society.)

Objective: Difficult-to-heal wound is a prevalent and significant complication of diabetes, characterized by impaired functionality of epithelial cells such as fibroblasts. This study aims to investigate the potential mechanism of ADSC-Exos promoting diabetic wound healing by regulating fibroblast function., Materials and Methods: ADSC-Exos were confirmed through TEM, NTA, and Western Blot techniques. The study conducted on rat skin fibroblasts (RSFs) exposed to 33 mmol/L glucose in vitro. We used cck-8, EDU, transwell, and scratch assays to verify the proliferation and migration of RSFs. Furthermore, levels of TGF-β1 and α-SMA proteins were determined by immunofluorescence and Western Blot. RSFs were transfected with miR-128-1-5p mimics and inhibitors, followed by quantification of TGF-β1, α-SMA, Col I and Smad2/3 protein levels using Western Blot. In vivo, the effects of ADSC-Exos on diabetic wounds were assessed using digital imaging, histological staining, as well as Western Blot analysis., Results: In vitro, ADSC-Exos significantly enhanced proliferation and migration of RSFs while reducing the expression of TGF-β1 and α-SMA. In vivo, ADSC-Exos effectively promoted diabetic wound healing and mitigated scar fibrosis. Additionally, ADSC-Exos exhibited elevated levels of miR-128-1-5p, which targets TGF-β1, resulting in a notable reduction in TGF-β1, α-SMA, Col I and smad2/3 phosphorylation in RSFs., Conclusion: In conclusion, our results demonstrated that ADSC-Exos promoted diabetic wound healing, and inhibited skin fibrosis by regulating miR-128-1-5p/TGF-β1/Smad signaling pathway, which provides a promising innovative treatment for diabetic wound healing., 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.)

Background: Asthma is a respiratory disease characterized by airway remodeling. We aimed to find out the role and mechanism of lncRNA MEG3 in asthma., Methods: We established a cellular model of asthma by inducing human airway smooth muscle cells (HASMCs) with PDGF-BB, and detected levels of lncRNA MEG3, miR-143-3p and FGF9 in HASMCs through qRT-PCR. The functions of lncRNA MEG3 or miR-143-3p on HASMCs were explored by cell transfection. The binding sites of miR-143-3p and FGF9 were subsequently analyzed with bioinformatics software, and validated with dual-luciferase reporter assay. MTT, 5-Ethynyl-2'-deoxyuridine (EdU) assay, and Transwell were used to detect the effects of lncRNA MEG3 or miR-143-3p on proliferation and migration of HASMCs. QRT-PCR and western blot assay were used to evaluate the level of proliferation-related marker PCNA in HASMCs., Results: The study found that lncRNA MEG3 negatively correlated with miR-143-3p, and miR-143-3p could directly target with FGF9. Silence of lncRNA MEG3 can suppress migration and proliferation of PDGF-BB-induced HASMCs via increasing miR-143-3p. Further mechanistic studies revealed that miR-143-3p negatively regulated FGF9 expression in HASMCs. MiR-143-3p could inhibit PDGF-BB-induced HASMCs migration and proliferation through downregulating FGF9., Conclusion: LncRNA MEG3 silencing could inhibit the migration and proliferation of HASMCs through regulating miR-143-3p/FGF9 signaling axis. These results imply that lncRNA MEG3 plays a protective role against asthma., (© 2024. The Author(s).)

Background: To uncover the clinical significance of LINC00858 in the development of Wilms' Tumor and the potential molecular mechanism., Methods: LINC00858 levels in Wilms' Tumor species and cell lines were determined by quantitative real-time polymerase chain reaction (qRT-PCR). The clinical significance of LINC00858 in influencing pathological features and prognosis in patients with Wilms' Tumor was analyzed. Proliferative and migratory changes in Wilms' Tumor cells with LINC00858 knockdown were assessed. The downstream gene of LINC00858 was verified by luciferase assay, and its involvement in the development of Wilms' Tumor was further explored., Results: LINC00858 was highly expressed in Wilms' Tumor tissues and cell lines. High level of LINC00858 was correlated to high rate of lymphatic metastasis and poor prognosis in patients with Wilms' Tumor. Knockdown of LINC00858 suppressed proliferative and migratory potentials in HFWT and 17-94 cells. MiR-653-5p was targeted by LINC00858. It was lowly expressed in Wilms' Tumor tissues and negatively regulated by LINC00858. Knockdown of miR-653-5p partially abolished the regulatory effects of LINC00858 on proliferative and migratory potentials in Wilms' Tumor cells., Conclusions: LINC00858 is highly expressed in Wilms' Tumor species and correlated to lymphatic metastasis rate and overall survival in patients with Wilms' Tumor. Knockdown of LINC00858 suppresses Wilms' Tumor cells to proliferate and migrate via targeting miR-653-3p.

As a member of the tumor necrosis factor receptor family, osteoprotegerin (OPG) is highly expressed in adults in the lung, heart, kidney, liver, spleen, thymus, prostate, ovary, small intestines, thyroid gland, lymph nodes, trachea, adrenal gland, the testis, and bone marrow. Together with the receptor activator of nuclear factor-κB (RANK) and the receptor activator of nuclear factor-κB ligand (RANKL), it forms the RANK/RANKL/OPG pathway, which plays an important role in the molecular mechanism of the development of various diseases. MicroRNAs (miRNAs) are a class of endogenous non-coding RNAs performing regulatory functions in eukaryotes, with a size of about 20-25 nucleotides. miRNA genes are transcribed into primary transcripts by RNA polymerase, bind to RNA-induced silencing complexes, identify target mRNAs through complementary base pairing, with a single miRNA being capable of targeting hundreds of mRNAs, and influence the expression of many genes through pathways involved in functional interactions. In recent years, a large number of studies have been done to explore the mechanism of action of miRNA in diseases through miRNA isolation, miRNA quantification, miRNA spectrum analysis, miRNA target detection, in vitro and in vivo regulation of miRNA levels, and other technologies. It was found that miRNA can play a key role in the pathogenesis of osteoporosis, rheumatoid arthritis, and other diseases by targeting OPG. The purpose of this review is to explore the interaction between miRNA and OPG in various diseases, and to propose new ideas for studying the mechanism of action of OPG in diseases., 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).)

Ethnopharmacological Relevance: The fruit of Lycium barbarum L. is widely employed with the traditional effect of tonic properties. According to the theory of traditional Chinese medicine, Gou Qi can be distributed in the meridian of stomach, as well as the liver and kidney, indicating its effect on the digestive system. Clinical studies found that Gou Qi enhanced gastrointestinal functions. Pharmacological research showed the extract of Lycium barbarum exhibiting a repaired effect on the intestine barrier. Lycibarbarspermidine L (LBS L), which belongs to polyamines, is separated from the fruit of Lycium barbarum. However, it is unknown whether LBS L can restore damaged intestinal barrier like other polyamines such as spermidine., Aim of the Study: To elucidate the recovery effect of LBS L on damaged intestinal epithelium and its miRNA-related mechanism., Materials and Methods: IEC-6 cells were used in vitro to assess the therapeutic effect of LBS L on the injured intestine and the regulation of miR-195-3p. Spermidine (SPD) with intestinal mucosal repair effect was used as a positive control. Sprague Dawley (SD) rats were subjected to 48 h fasting to induce intestinal epithelial atrophy in vivo. To determine the therapeutic effect of LBS L on injured intestinal epithelium and explore the mechanism, the fasting model group rats were treated with LBS L (25 mg/kg) for 4 days., Results: Results in vitro showed that LBS L (10 μM) promoted cell proliferation and migration, affecting the S phase of the cell cycle. Western blot signals showed that LBS L raised the expression level of occludin. The miR-195-3p levels were decreased following LBS L treatment, which could be inversed by transfecting miR-195-3p mimic, demonstrating that LBS L inhibited miR-195-3p to improve cell growth. Results in vivo showed that LBS L could reverse the atrophic villi and inflammatory cell infiltration in the submucosa and restore miR-195-3p, occludin, and Ki67 levels in the intestine of mice in the fasting group., Conclusions: LBS L restores injured intestinal epithelium by reducing the expression of miR-195-3p., Competing Interests: Declaration of competing interest No conflict of interest exists regarding this manuscript.., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Turmeric (Curcuma longa) has been used to treat gastrointestinal disorders in the Indian Ayurvedic medical system. According to the theory behind traditional Chinese medicine, turmeric can be distributed in the spleen meridian, for which it has been used as a digestive aid. Curcumin (Cur), a natural polyphenol compound originally derived from turmeric, has anti-inflammatory activity and can assist in treating inflammatory bowel disease., Aims of the Study: To investigate curcumin's protective effects on intestinal epithelium and explore the underlying miR-195-3p-related mechanisms., Materials and Methods: The miR-195-3p mimics were used to over-express miR-195-3p. The in vitro effects of Cur and miR-195-3p on the intestine were shown utilizing intestinal cryptlike epithelial cell line-6 (IEC-6) cells. By fasting for 48 h, an intestinal mucosal atrophy model of SD rats was created in vivo. Cur (25 or 50 mg/kg) was assessed for its protective effect on intestinal epithelium. Glycyrrhetinic acid (GA) with an intestinal protective effect reported in our previous research was adopted as a positive drug for the in vivo and in vitro bioactivity evaluation since there is no universally positive drug for either intestinal mucosal restitution or miR-195-3p modulation., Results: Cur protects the intestinal epithelium and promotes its repair after injury via down-regulating miR-195-3p. In vitro experiments showed that Cur inhibited the apoptosis of IEC-6 cells, stimulated their growth, and down-regulated the level of miR-195-3p in cells. When miR-195-3p was overexpressed, the viability of IEC-6 cells decreased while the apoptosis rate increased. All the above detrimental effects were alleviated after curcumin intervention. Moreover, Cur reversed the effect of miR-195-3p on its downstream occludin. In vivo, results showed that 48-h fasting impaired the integrity of the small intestinal mucosa (abnormal crypt structure and reduced goblet cell number), which was ameliorated by Cur treatment. In addition, the Cur treatment reversed both the increased expression level of miR-195-3p and decreased levels of ki-67 and occludin caused by fasting., Conclusions: Cur could promote the proliferation and repair after injury of the intestinal mucosa by down-regulating miR-195-3p., Competing Interests: Declaration of competing interest The authors declare no competing interests. We have no financial and personal relationships with other people or organizations that can inappropriately influence our work. There is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: To investigate the protective effect of Xuebijing injection on acute lung injury (ALI) associated with cardiopulmonary bypass (CPB) by regulating the apoptosis of polymorphonuclear neutrophils (PMN)., Methods: Thirty male Sprague-Dawley (SD) rats were randomly divided into sham operation group (Sham group), CPB model group (CPB group) and Xuebijing pretreatment group (XBJ group) according to the random number table method, with 10 rats in each group. Rats in the CPB group and XBJ group undergoing CPB procedures for 60 minutes. Rats in the Sham group did not undergo CPB. Rats in the XBJ group received intraperitoneal injection of 4 mL/kg Xuebijing injection 2 hours before CPB. Rats in the Sham group and CPB group were injected with an equal amount of normal saline. 4 hours after CPB, arterial blood was collected for blood gas analysis to calculate respiratory index (RI), and lung tissue of rats was collected for determination of lung index (LI) and pulmonary water containing rate. PMN in bronchoalveolar lavage fluid (BALF) were collected and the activity of caspase-3 was detected. The apoptosis rate was detected by flow cytometry. The expressions of microRNA-142-3p (miR-142-3p) and FoxO1 mRNA were detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). The protein expression of FoxO1 was detected by Western blotting. In addition, HL-60 cells were divided into control oligonucleotide transfection group, miR-142-3p mimics transfection group, and miR-142-3p inhibitor transfection group. After 48 hours of transfection, the activity of miR-142-3p binding to FoxO1 was detected using dual luciferase reporter genes., Results: Compared with Sham group, RI, LI and pulmonary water containing rate were significantly increased in CPB group. The caspase-3 activity and apoptosis rate of PMN obtained from BALF were significantly decreased, the expression of miR-142-3p was decreased, and the expression of FoxO1 protein was increased. However, compared with CPB group, RI, LI and pulmonary water containing rate were significantly decreased in XBJ group [RI: 0.281±0.066 vs. 0.379±0.071, LI: 4.50±0.26 vs. 5.71±0.42, pulmonary water containing rate: (80.31±32.50)% vs. (84.59±3.41)%, all P < 0.01]. The caspase-3 activity and apoptosis rate of PMN obtained from BALF were significantly increased [caspase-3 activity: 0.350±0.021 vs. 0.210±0.014, apoptosis rate: (15.490±1.382)% vs. (8.700±0.701)%, both P < 0.01], the expression of miR-142-3p was significantly up-regulated (2 -ΔΔCt : 2.61±0.17 vs. 0.62±0.05, P < 0.01), and the protein expression of FoxO1 was decreased [FoxO1/GAPDH (relative expression level): 0.81±0.04 vs. 1.22±0.06, P < 0.01]. However, there was no statistically significant difference in FoxO1 mRNA expression among the three groups. The bioinformatics analysis results showed that miR-142-3p can bind to the FoxO1 3'untranslated region (3'UTR). In HL-60 cells, compared with control oligonucleotide transfection group, the transfection of miR-142-3p mimics could reduce the expression of FoxO1 protein [FoxO1/GAPDH (relative expression level): 0.48±0.06 vs. 1.00±0.05, P < 0.01], however, the transfection of miR-142-3p inhibitor increased the expression of FoxO1 protein [FoxO1/GAPDH (relative expression level): 1.37±0.21 vs. 1.00±0.05, P < 0.05]. But, transfection with miR-142-3p mimics or inhibitor had no effect on FoxO1 mRNA expression. The luciferase reporter gene showed that miR-142-3p could bind to the FoxO1 3'UTR to inhibit FoxO1 expression., Conclusions: Xuebijing injection may promote the apoptosis of pulmonary alveolar PMN through the miR-142-3p/FoxO1 axis, and play a role in the prevention and treatment of CPB-induced ALI.

When hematopoietic cells are overwhelmed with ionizing radiation (IR) DNA damage, the alternative non-homologous end-joining (aNHEJ) repair pathway is activated to repair stressed replication forks. While aNHEJ can rescue cells overwhelmed with DNA damage, it can also mediate chromosomal deletions and fusions, which can cause mis-segregation in mitosis and resultant aneuploidy. We previously reported that a hematopoietic microRNA, miR-223-3p, normally represses aNHEJ. We found that miR-223 -/- mice have increased survival of hematopoietic stem and progenitor cells (HSPCs) after sublethal IR. However, this came at the cost of significantly more genomic aberrancies, with miR-223 -/- hematopoietic progenitors having increased metaphase aberrancies, including chromothripsis, and increased sequence abnormalities, especially deletions, which is consistent with aNHEJ. These data imply that when an HSPC is faced with substantial DNA damage, it may trade genomic damage for its own survival by choosing the aNHEJ repair pathway, and this choice is regulated in part by miR-223-3p., Competing Interests: Conflict of Interest Disclosure The authors do not have any relevant conflicts of interest to disclose in relation to this work., (Copyright © 2023 ISEH -- Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.)

Cervical cancer (CC) is a common malignant neoplasm in gynecology. There is increasing evidence to suggest that microRNAs (miRNAs) act as crucial regulators of CC. However, whether miR-10a-5p plays a role in CC is under investigation. The aim of this stuy was to assess the miR-10a-5p expression pattern in the development of CC and investigate its downstream target. MiR-10a-5p inhibition decreased CC cell proliferation and impaired CC cell invasion and migration but enhanced apoptosis. UBE2I was a direct target of miR-10a-5p. QRT-PCR results showed a down-regulation of UBE2I in CC cells, opposing miR-10a-5p. Besides, overexpression of miR-10a-5p down-regulated UBE2I. Functional rescue experiments further indicated the miR-10a-5p-UBE2I axis was linked to CC cell growth, apoptosis and metastasis. MiR-10a-5p upregulation promotes cervical cancer development by inhibiting UBE2I. These results also predict that miR-10a-5p may be a potential target for the clinical treatment of CC.IMPACT STATEMENT What is already known on this subject? As a widely researched cancer-related miRNA, the overexpression of miR-10a-5p has been verified in various cancers. It has been described in a meta-analysis report that there were 42 miRNAs up-regulated and 21 miRNAs down-regulated in different stages of cervical cancer tissue versus healthy tissue. What do the results of this study add? We verified that miR-10a-5p initiates and promotes tumor cell development by decreasing UBE2I abundance. This miR-10a-5p-mediated post-transcriptional regulation of UBE2I is involved in the tumorigenesis, invasion and migration of human cervical cancer. What are the implications of these findings for clinical practice and/or further research? These findings provide mechanistic insights into how miR-10a-5p regulates cervical cancer hyper-proliferation and metastasis, as well as a new target for clinical treatment. Nevertheless, whether miR-10a-5p/UBE2I axis can be regulated by non-invasive methods need further exploration, which will be the focus of our future research.

Long non-coding RNAs (lncRNAs) are important regulators in plant growth and development. Here the function of a lncRNA fragment was studied, which was predicted as an endogenous target mimic (eTM) of miR156 in Brassica campesrtis. Unexpectedly, the transformation of this lncRNA into Arabidopsis thaliana neither inhibited the expression of miR156a nor resulted in any phenotypes that differed from the control plants (CK). The full-length sequence of the lncRNA (named bra-miR156HG) was then obtained using RACE and transferred into A. thaliana. The transgenic plants displayed a delay in flowering time, an increasing number of rosette leaves, and a changed morphology of cauline leaves, which was similar to the plants that expressed bra-miR156a. In contrast, the overexpression of bra-miR156HG in B. campestris resulted in an increased tip angle of leaves and changed the length-width ratio of leaves at different nodes, suggesting that bra-miR156HG may be involved in regulating the leaf morphology. Collectively, our study showed that bra-miR156HG functions as a precursor of bra-miR156a involved in regulating plant flowering time and leaf development under different biological backgrounds. The secondary structure of lncRNA is essential not only for the normal roles that it plays but also for expanding the functional diversities., 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 © 2023 Elsevier B.V. All rights reserved.)

Importance: The synergy of two oncogenic retroviruses is an essential phenomenon in nature. The synergistic replication of ALV-J and REV in poultry flocks increases immunosuppression and pathogenicity, extends the tumor spectrum, and accelerates viral evolution, causing substantial economic losses to the poultry industry. However, the mechanism of synergistic replication between ALV-J and REV is still incompletely elusive. We observed that microRNA-155 targets a dual pathway, PRKCI-MAPK8 and TIMP3-MMP2, interacting with the U3 region of ALV-J and REV, enabling synergistic replication. This work gives us new targets to modulate ALV-J and REV's synergistic replication, guiding future research on the mechanism., Competing Interests: The authors declare no conflict of interest.

Background: Trabecular meshwork (TM) dysfunction-induced elevation of intraocular pressure has been identified as the main risk factor of irreversible optic nerve injury in Primary open‑angle glaucoma (POAG). Increasing evidences suggest that microRNA (miRNA) plays a vital role in the pathogenesis of POAG. This study aims to construct a miRNA-mRNA regulatory network and identify biomarkers for POAG., Methods: miRNAs and mRNAs expression profiling of TM samples from controls and POAG patients were assessed through microarray analysis. Target genes of differentially expressed miRNAs (DEmiRNAs) were predicted by miEAA and miRNet. Then GO and KEGG pathway analysis of differentially expressed mRNAs (DEmRNAs) were performed. PPI of top 30 hub genes was identified and miRNA-mRNA network was established by STRING database and Cytoscape software. GSE27276 and GSE105269 datasets were used to verify the expression of hub genes and to predict potential biomarkers in TM and aqueous humor (AH) for POAG, respectively. Finally, GSEA analysis was conducted to estimate the main signaling pathway of POAG pathogenesis., Results: A total of 29 up-regulated and 7 down-regulated miRNAs, 923 up-regulated and 887 down-regulated mRNAs were identified in TM of POAG compared with controls. Target genes and DEmRNAs were mainly enriched in nitric oxide biosynthetic process, vasopressin-regulated water reabsorption, and so on. Through miRNA-mRNA network construction, top 30 hub genes were regulated by 24 DEmiRNAs. 8 genes were aberrantly expressed in dataset GSE27276. 3 genes (CREB1, CAPZA2, SLC2A3) and 2 miRNAs (miR-106b-5p, miR-15a-5p) were identified as potential biomarkers for POAG in TM and AH, respectively. GSEA analysis revealed that these 3 genes modulated POAG through different pathways., Conclusion: In this study, construction of miRNA-mRNA network and identification of biomarkers provide a novel insight into the pathogenesis, early diagnosis and treatment for POAG., (© 2023. The Author(s).)

Several studies have elucidated the pivotal function that long noncoding RNAs (lncRNAs) exerted on the initiation and development of various human carcinomas, encompassing non-small cell lung cancer (NSCLC). In spite of the fact that lncRNA MAPKAPK5 antisense RNA 1 (MAPKAPK5-AS1) has already been investigated by researchers and confirmed to play oncogenic roles in colorectal cancer, the underlying regulatory function of MAPKAPK5-AS1 in NSCLC cells still remain unclear. In our research, we found that MAPKAPK5-AS1 was expressed at high levels in NSCLC cells. Biological functional assays unclosed that downregulation of MAPKAPK5-AS1 repressed proliferative and migratory capacities whereas promoted apoptotic level in NSCLC cells. Molecular mechanism experiments confirmed that, in NSCLC cells, MAPKAPK5-AS1 combined with miR-515-5p and negatively modulated miR-515-5p expression level. Besides, calcium-binding protein 39 (CAB39) expression level was verified to be negatively modulated by miR-515-5p whereas positively modulated by MAPKAPK5-AS1 in NSCLC cells. Furthermore, rescued-function assays disclosed that inhibited miR-515-5p expression or overexpressed CAB39 could restore the suppressive influence of MAPKAPK5-AS1 silence on NSCLC progression. In summary, MAPKAPK5-AS1 upregulates CAB39 expression level to facilitate NSCLC progression by sequestering miR-515-5p, providing promising biomarkers for NSCLC treatment., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disease that affects women of reproductive age. It is also a significant cause of infertility. Circular RNAs have been found to have a crucial role in the development and progression of reproductive system diseases. In this study, we focused on circ&#95;BECN1 and aimed to investigate its role and mechanism in PCOS, providing a foundation for early diagnosis and treatment of this condition. Our findings revealed an upregulation of circ&#95;BECN1 expression in the ovarian granulosa cells (GCs) of PCOS patients. Additionally, the silencing of circ&#95;BECN1 resulted in inhibited proliferation and enhanced apoptosis of the human ovarian granulosa-like tumor cell line (KGN), therefore implicating circ&#95;BECN1 in the cell cycle process. Through a dual-luciferase reporting assay, we determined that circ&#95;BECN1 acts as a sponge for miR-619-5p and that Rab5b is the target gene of miR-619-5p. Moreover, the expression of Rab5b was found to be upregulated in the ovarian tissue of PCOS patients. Knocking down circ&#95;BECN1 resulted in decreased Rab5b expression, which was then restored by using a miR-619-5p inhibitor. Additionally, rescue experiments demonstrated that overexpressing Rab5b reversed the effects of circ&#95;BECN1 knockdown on cell proliferation and apoptosis in KGN cells. In summary, our findings indicate that circ&#95;BECN1 is upregulated in PCOS GCs and promotes cell growth and cell cycle progression, and reduces cell apoptosis by modulating the miR-619-5p/Rab5b axis. Therefore, circ&#95;BECN1 may serve as a potential therapeutic target for PCOS treatment., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Renal cell carcinoma (RCC) accounts for approximately 2-3% of all adult malignancies. Clear cell renal cell carcinoma (ccRCC), which comprises 70-80% of all RCC cases, is the most common histological subtype., Methods: ccRCC transcriptome data and clinical information were downloaded from the TCGA database. We used the TCGA and GEPIA databases to analyze relative expression of BMP1 in various types of human cancer. GEPIA was used to perform survival analysis for BMP1 in various cancer types. Upstream binding miRNAs of BMP1 were obtained through several important target gene prediction tools. StarBase was used to predict candidate miRNAs that may bind to BMP1 and candidate lncRNAs that may bind to hsa-miR-532-3p. We analyzed the association between expression of BMP1 and immune cell infiltration levels in ccRCC using the TIMER website. The relationship between BMP1 expression levels and immune checkpoint expression levels was also investigated., Results: BMP1 was upregulated in GBM, HNSC, KIRC, KIRP and STAD and downregulated in KICH and PRAD. Combined with OS and DFS, BMP1 can be used as a biomarker for poor prognosis among patients with KIRC. Through expression analysis, survival analysis and correlation analysis, LINC00685, SLC16A1-AS1, PVT1, VPS9D1-AS1, SNHG15 and the CCDC18-AS1/hsa-miR-532-3p/BMP1 axis were established as the most potential upstream ncRNA-related pathways of BMP1 in ccRCC. Furthermore, we found that BMP1 levels correlated significantly positively with tumor immune cell infiltration, biomarkers of immune cells, and immune checkpoint expression., Conclusion: Our results demonstrate that ncRNA-mediated high expression of BMP1 is associated with poor prognosis and tumor immune infiltration in ccRCC., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Female mosquitoes need a blood meal after mating for their eggs to develop, and this behavior leads to the spread of pathogens. Therefore, understanding the molecular regulation of reproduction in female mosquitoes is essential to control mosquito vector populations. In this study, we reported that microRNA-989 (miR-989), which targets 5-HTR1 (encoding secreted 5-hydroxytryptamine receptor1), is essential for mosquito reproduction., Methods: The spatiotemporal expression profile of miR-989 was detected using quantitative real-time reverse transcription PCR (RT-qPCR). miR-989 antagomirs and antagomir-negative control (NC) were designed and synthesized to knock down the expression of endogenous miR-989 in female mosquitoes. RNA sequencing was used to analyze the ovarian response to miR-989 deletion. The targets of miR-989 were predicted and confirmed using RNAhybrid and dual-luciferase assays., Results: miR-989 is exclusively expressed in female mosquito ovaries and responds to blood feeding. Injection of the miR-989 antagomir resulted in smaller ovaries and reduced egg production. 5-HTR1 was demonstrated as a target of miR-989. The deletion of miR-989 contributed to the upregulation of 5-HTR1 expression. Knockdown of 5-HTR1 rescued the adverse egg production caused by miR-989 silencing. Thus, miR-989 might play an essential role in female reproduction by targeting 5-HTR1., Conclusions: We found that miR-989 targets 5-HTR1 and participates in the regulation of reproduction in female mosquitoes. These findings expand our understanding of reproduction-related miRNAs and promote new control strategies for mosquitoes., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Osteosarcoma (OS), which is a common and aggressive primary bone malignancy, occurs mainly in children and adolescent. Long noncoding RNAs (lncRNAs) are reported to play a pivotal role in various cancers. Here, we found that the lncRNA HOTAIRM1 is upregulated in OS cells and tissues. A set of functional experiments suggested that HOTAIRM1 knockdown attenuated the proliferation and stimulated the apoptosis of OS cells. A subsequent mechanistic study revealed that HOTAIRM1 functions as a competing endogenous RNA to elevate ras homologue enriched in brain (Rheb) expression by sponging miR-664b-3p. Immediately afterward, upregulated Rheb facilitates proliferation and suppresses apoptosis by promoting the mTOR pathway-mediated Warburg effect in OS. In summary, our findings demonstrated that HOTAIRM1 promotes the proliferation and suppresses the apoptosis of OS cells by enhancing the Warburg effect via the miR-664b-3p/Rheb/mTOR axis. Understanding the underlying mechanisms and targeting the HOTAIRM1/miR-664b-3p/Rheb/mTOR axis are essential for OS clinical treatment., (© 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

The study aims to summarize topical and frontier issues in sepsis and exosomes and provide advice and resources for researchers working in related disciplines. Publications on exosomes in sepsis from 2004 to 2022 were extracted from the Web of Science Core Collection database. VOSviewer 1.6.18 and CiteSpace 6.1.3 were used to conduct the bibliometric analysis. The number of publications on exosomes in sepsis showed a rapidly rising trend globally. China and the United States were the most published countries. Shanghai Jiao Tong University is the most prolific institution. Frontiers in Immunology was one of the journals with the highest number of papers. Journal of Immunology was the most co-cited journal. Ping Wang was the most productive author. Clotilde Thery was the author who has been cited the most times among co-cited authors. Singer m, 2016, Jama-j am med assoc was the most co-cited reference. "Mesenchymal stem cells derived exosomes," "microRNAs," "apoptosis," and "immunomodulatory therapy" are the current research hot spots and frontiers. This study provides a comprehensive overview of the current status and trends in sepsis and exosomal research. Researchers working in this area will benefit from the hot spots and trends of exosomes in sepsis discovered through this study., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

MicroRNAs (miRNA) play critical roles in diverse biological processes of diseases. Inferring potential disease-miRNA associations enable us to better understand the development and diagnosis of complex human diseases via computational algorithms. The work presents a variational gated autoencoder-based feature extraction model to extract complex contextual features for inferring potential disease-miRNA associations. Specifically, our model fuses three different similarities of miRNAs into a comprehensive miRNA network and then combines two various similarities of diseases into a comprehensive disease network, respectively. Then, a novel graph autoencoder is designed to extract multilevel representations based on variational gate mechanisms from heterogeneous networks of miRNAs and diseases. Finally, a gate-based association predictor is devised to combine multiscale representations of miRNAs and diseases via a novel contrastive cross-entropy function, and then infer disease-miRNA associations. Experimental results indicate that our proposed model achieves remarkable association prediction performance, proving the efficacy of the variational gate mechanism and contrastive cross-entropy loss for inferring disease-miRNA associations., 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 © 2023 Elsevier Ltd. All rights reserved.)

Periodontitis is a microbial-related chronic inflammatory disease associated with imbalanced differentiation of Th17 cells and Treg cells. Bone marrow-derived mesenchymal stem cells (BM-MSCs) possess wide immunoregulatory properties. Long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) contribute to the immunomodulation in the pathological mechanisms of inflammatory diseases. However, critical lncRNAs/miRNAs involved in immunomodulation of mandibular BM-MSCs largely remain to be identified. Here, we explored the molecular mechanisms behind the defective immunomodulatory ability of mandibular BM-MSCs under the periodontitis settings. We found that mandibular BM-MSCs from P. gingivalis -induced periodontitis mice had significantly reduced expression of LncRNA SPIRE1 than that from normal control mice. LncRNA SPIRE1 knockdown in normal BM-MSCs caused Th17/Treg cell differentiation imbalance during the coculturing of BM-MSCs and CD4 T cells. In addition, LncRNA SPIRE1 was identified as a competitive endogenous RNA that sponges miR-181a-5p in BM-MSCs. Moreover, miR-181a-5p inhibition attenuated the impact of LncRNA SPIRE1 knockdown on the ability of BM-MSCs in modulating Th17/Treg balance. Prolactin receptor (PRLR) was validated as a downstream target of miR-181a-5p. Notably, targeted knockdown of LncRNA SPIRE1 or PRLR or transfection of miR-181a-5p mimics activated the JAK/STAT3 signaling in normal BM-MSCs, while treatment with STAT3 inhibitor C188-9 restored the immunomodulatory properties of periodontitis-associated BM-MSCs. Furthermore, BM-MSCs with miR-181a-5p inhibition or PRLR-overexpression showed enhanced in vivo immunosuppressive properties in the periodontitis mouse model. Our results indicate that the JAK/STAT3 pathway is involved in the immunoregulation of BM-MSCs, and provide critical insights into the development of novel targeted therapies against periodontitis.

Substantial morbidity and mortality are associated with postcardiac arrest brain injury (PCABI). MicroRNAs(miRNAs) are essential regulators of neuronal metabolism processes and have been shown to contribute to alleviated neurological injury after cardiac arrest. In this study, we identified miRNAs related to the prognosis of patients with neurological dysfunction after cardiopulmonary resuscitation based on data obtained from the Gene Expression Omnibus (GEO) database. Then, we explored the effects of miR-483-5p on mitochondrial biogenesis, mitochondrial-dependent apoptosis, and oxidative stress levels after ischemia‒reperfusion injury in vitro and in vivo. MiR-483-5p was downregulated in PC12 cells and hippocampal samples compared with that in normal group cells and hippocampi. Overexpression of miR-483-5p increased the viability of PC12 cells after ischemia‒reperfusion injury and reduced the proportion of dead cells. A western blot analysis showed that miR-483-5p increased the protein expression of PCG-1, NRF1, and TFAM and reduced the protein expression of Bax and cleaved caspase 3, inhibiting the release of cytochrome c from mitochondria and alleviating oxidative stress injury by inhibiting the production of ROS and reducing MDA activity. We confirmed that miR-483-5p targeted TNFSF8 to regulate the AMPK/JNK pathway, thereby playing a neuroprotective role after cardiopulmonary resuscitation. Hence, this study provides further insights into strategies for inhibiting neurological impairment after cardiopulmonary resuscitation and suggests a potential therapeutic target for PCABI., (© 2022. The Author(s).)

Migrasomes comprise a recently identified unique type of extracellular vesicle (EV) containing varying numbers of small vesicles. However, the final fate of these small vesicles is still unclear. Here, we report the discovery of EV-like migrasome-derived nanoparticles (MDNPs) that are produced by migrasomes releasing internal vesicles via self-rupture and through a process similar to cell plasma membrane budding. Our results demonstrate that MDNPs have a membrane structure with a typical round-shaped morphology and have the characteristic markers of migrasomes, but do not present the markers of EVs from the cell culture supernatant. More importantly, we also show that MDNPs are loaded with a large number of microRNAs different from those found in migrasomes and EVs. Our results provide evidence that migrasomes can produce EV-like nanoparticles. These findings have important implications for understanding the unknown biological functions of migrasomes., (© 2023 Federation of European Biochemical Societies.)

Mesenchymal stem cells (MSCs)-derived exosomes are demonstrated to exert neuroprotective effects in stroke. We aimed to explore the role and mechanism of long non-coding RNA (lncRNA) KLF3 antisense RNA 1 (KLF3-AS1) in bone marrow mesenchymal stem cells-derived exosomes (BMSCs-Exos) in cerebral ischemia/reperfusion (I/R) injury. Exosomes were isolated from the culture medium of BMSCs. A mouse model of middle cerebral artery occlusion (MCAO) in vivo and a BV-2 cell model of oxygen and glucose deprivation/reoxygenation (OGD/RX) in vitro were established. Cell viability and apoptosis were detected using MTT assay, TUNEL staining and flow cytometry, respectively. Related proteins were determined with western blot and immunohistochemistry, while related RNAs were analyzed by RT-qPCR. Neurological deficit and cerebral infarct volume were evaluated by the modified neurological severity score (mNSS) and TTC staining, respectively. Our observations indicate that exosomes derived from BMSCs-preconditioned medium exerted neuroprotective effects, as indicated by the increased cell viability and the suppressed apoptosis in OGD/RX-suffered BV-2 cells. KLF3-AS1 expression was upregulated in BMSCs-Exos. Furthermore, KLF3-AS1 knockdown antagonized the protective effects of BMSCs-Exos. Mechanistically, BMSCs-Exos carrying KLF3-AS1 inhibited apoptosis via enhancing autophagy. KLF3-AS1 was found to recruit ETS variant transcription factor 4 (ETV4), which upregulated Sirt1 expression. Knockdown of KLF3-AS1 neutralized the protective effects of BMSCs-Exos on MCAO-induced brain injury, which was then reversed by the treatment with Sirt1 inhibitor EX527. We concluded that KLF3-AS1 derived from BMSCs-Exos promoted autophagy to alleviate I/R injury via ETV4/Sirt1 axis., (Copyright © 2023 IBRO. Published by Elsevier Ltd. All rights reserved.)

Replication factor C 5 (RFC5) is involved in a variety of biological functions of cancer. However, the expression pattern of RFC5 and the underlying mechanisms in colorectal cancer (CRC) remain elusive. Here, we show that RFC5 is significantly upregulated in CRC tissues and cells. Patients with CRC and increased RFC5 levels have an unfavorable prognosis. RFC5 can promote the proliferation, migration, and invasion of CRC cells and inhibit the apoptosis of CRC cells. Additionally, upstream of RFC5, we constructed the competing endogenous RNA network and confirmed that RFC5 in this network was inhibited by miR-3614-5p by directly targeting its 3'-untranslated regions. We verified that circ&#95;0038985, which is positively correlated with RFC5, directly targeted miR-3614-5p. Overexpression of circ&#95;0038985 promoted CRC cell migration and invasion, and these effects were partially reversed by the reintroduction of miR-3614-5p. Moreover, we found that RFC5 may promote the vascular endothelial growth factor A (VEGFa)/vascular endothelial growth factor receptor 2 (VEGFR2)/extracellular signal-regulated protein kinase (ERK) pathway. The knockdown of RFC5 reduced CRC tumorigenesis in vivo. Collectively, these data demonstrate that the circ&#95;0038985/miR-3614-5p/RFC5 axis plays a critical role in the progression of CRC, and RFC5 may promote CRC progression by affecting the VEGFa/VEGFR2/ERK pathway., (© 2023 Wiley Periodicals LLC.)

Background: Polymorphisms in microRNAs (miRNAs) play an important role in acute coronary syndromes (ACS). The purpose of this study was to assess the association of miR-146a rs2910164 and miR-34b rs4938723 polymorphisms with the development and prognosis of ACS and to explore the underlying mechanisms., Methods: A case-control study of 1171 subjects was included to determine the association of miR-146a rs2910164 and miR-34b rs4938723 polymorphisms with ACS risk. An additional 612 patients with different miR-146a rs2910164 genotypes, who underwent percutaneous coronary intervention (PCI) were included in the validation cohort and followed for 14 to 60 months. The endpoint was major adverse cardiovascular events (MACE). A luciferase reporter gene assay was used to validate the interaction of oxi-miR-146a(G) with the IKBA 3'UTR. Potential mechanisms were validated using immunoblotting and immunostaining., Results: The miR-146a rs2910164 polymorphism was significantly associated with the risk of ACS (Dominant model: CG + GG vs. CC, OR = 1.270, 95% CI (1.000-1.613), P = 0.049; Recessive model: GG vs. CC + CG, OR = 1.402, 95% CI (1.017-1.934), P = 0.039). Serum inflammatory factor levels were higher in patients with the miR-146a rs2910164 G allele than in those with the C allele. MiR-146a rs2910164 polymorphism in dominant model was associated with the incidence of MACE in post-PCI patients (CG + GG vs. CC, HR = 1.405, 95% CI (1.018-1.939), P = 0.038). However, the miR-34b rs4938723 polymorphism was not associated with the prevalence and prognosis of ACS. The G allele of miR-146a rs2910164 tends to be oxidized in ACS patients. The miRNA fractions purified from monocytes isolated from ACS patients were recognized by the 8OHG antibody. Mispairing of Oxi-miR-146a(G) with the 3'UTR of IKBA results in decreased IκBα protein expression and activation of the NF-κB inflammatory pathway. P65 expression was higher in atherosclerotic plaques from patients carrying the miR-146a rs2910164 G allele., Conclusion: The variant of miR-146a rs2910164 is closely associated with the risk of ACS in Chinese Han population. Patients carrying miR-146a rs2910164 G allele may have worse pathological change and poorer post-PCI prognosis, partly due to the oxidatively modified miR-146a mispairing with 3'UTR of IKBA and activating NF-κB inflammatory pathways., (© 2023. The Author(s).)

Innate immunity is the first line of host defense against pathogenic invasion in metazoans. The transcription factor basic leucine zipper transcriptional factor ATF-like 3 (BATF3) plays a crucial role in the development of conventional dendritic cells and the program of CD8 + T cell survival and memory, but the role of BATF3 in innate immune responses remains unclear. Here, we show an evolutionarily conserved basic-region leucine zipper (bZIP) transcription factor BATF3/ZIP-10 suppresses innate immune response through repressing the p38/PMK-1 mitogen-activated protein kinase (MAPK) pathway in vitro and in vivo. The worm mutant lacking the Caenorhabditis elegans homolog BATF3, ZIP-10, exhibited enhanced resistance to PA14 infection, which was completely rescued by transgenic expression of either endogenous zip-10 or mouse or human Batf3 cDNA driven by the worm zip-10 promoter. ZIP-10 expression was inhibited by a microRNA miR-60 that was downregulated upon PA14 infection. Moreover, the level of phosphorylated but not total PMK-1/p38 was attenuated by ZIP-10 and stimulated by miR-60. The human HEK293 cells with Batf3 overexpression or RNA-interference knockdown exhibited a reduction or increase of the cell viability upon Pseudomonas aeruginosa PA14 infection, respectively. The overexpression of either worm ZIP-10 or human BATF3 abolished the activation of p38 and inhibited the expression of antimicrobial peptides and cytokine genes in HEK293 cells. Our findings indicate that the genetic transcriptional program of the evolutionally conserved bZIP transcription factor BATF3/ZIP-10 suppresses innate immunity by attenuating the p38 MAPK signaling activity, which expands our understanding of the pathological mechanisms underlying relevant infectious diseases., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Japanese Society for Immunology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Circular RNAs (circRNAs) are a new family of abundant regulatory RNAs with roles in various types of cancer. While the hsa&#95;circ&#95;0046701 (circ-YES1) function in non-small cell lung cancer (NSCLC) is unclear., Methods: Circ-YES1 expression in normal pulmonary epithelial and NSCLC cells was examined. The small interfering RNA for circ-YES1 was prepared, cell proliferation and migration were assessed. Tumorigenesis in nude mice was assayed to validate the role of circ-YES1. Bioinformatics analyses and luciferase reporter assays were utilized to identify downstream targets of circ-YES1., Results: Compared to normal pulmonary epithelial cells, the circ-YES1 expression increased in NSCLC cells, and cell proliferation and migration were suppressed after circ-YES1 knockdown. Both high mobility group protein B1 (HMGB1) and miR-142-3p were found to be downstream targets of circ-YES1, and miR-142-3p inhibition and HMGB1 overexpression reversed the effects of circ-YES1 knockdown on cell proliferation and migration. Similarly, HMGB1 overexpression reversed the miR-142-3p overexpression effects on these two processes. The imaging experiment results revealed that circ-YES1 knockdown impeded tumor development and metastasis in a nude mouse xenograft model., Conclusion: Taken together, our results show that circ-YES1 promotes tumor development through the miR-142-3p-HMGB1 axis and support the development of circ-YES1 probability as a new therapeutic NSCLC target., (© 2023. The Author(s).)

Background: Circular RNAs (circRNAs) mediate the progression of human cancers, including oral squamous cell carcinoma (OSCC). The aim of this study was to investigate the functions of circRNA CDR1 Antisense RNA (circCDR1as) in OSCC. Moreover, the relationships among circCDR1as, microRNA-876-5p (miR-876-5p) and Solute Carrier Family 7 Member 11 (SLC7A11) in OSCC development were explored., Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to determine the expression of circCDR1as, miR-876-5p, and SLC7A11. Cell Counting kit-8 assay, cell colony formation assay, and 5-ethynyl-2'-deoxyuridine (EDU) assay were used to assess cell proliferation. Transwell assay was adopted for cell migration and invasion., Results: CircCDR1as level was aberrantly elevated in OSCC tissues and cells. Overexpression of circCDR1as promoted autophagy, cell cycle, proliferation, and metastasis and repressed apoptosis in OSCC cells. CircCDR1as directly targeted miR-876-5p and miR-876-5p interacted with SLC7A11. MiR-876-5p overexpression reversed the effects of circCDR1as elevation on OSCC cell autophagy, cell cycle, growth, motility, and apoptosis. Inhibition of miR-876-5p aggravated the malignant behaviors of OSCC cells, while SLC7A11 silencing ameliorated the impacts. In addition, circCDR1as knockdown blocked tumor growth in vivo., Conclusion: CircCDR1as acted as an oncogene in OSCC progression through elevating SLC7A11 by targeting miR-876-5p., (© 2021 Wiley Periodicals LLC.)

Long noncoding RNAs (lncRNAs) are pivotal regulators in gene expression and diverse biological processes, such as immune defense and host-pathogen interactions. However, little is known about the roles of lncRNAs in the response of the Asian honey bee ( Apis cerana ) to microsporidian infestation. Based on our previously obtained high-quality transcriptome datasets from the midgut tissues of Apis cerana cerana workers at 7 days post inoculation (dpi) and 10 dpi with Nosema ceranae (AcT7 and AcT10 groups) and the corresponding un-inoculated midgut tissues (AcCK7 and AcCK10 groups), the transcriptome-wide identification and structural characterization of lncRNAs were conducted, and the differential expression pattern of lncRNAs was then analyzed, followed by investigation of the regulatory roles of differentially expressed lncRNAs (DElncRNAs) in host response. Here, 2365, 2322, 2487, and 1986 lncRNAs were, respectively, identified in the AcCK7, AcT7, AcCK7, and AcT10 groups. After removing redundant ones, a total of 3496 A. c. cerana lncRNAs were identified, which shared similar structural characteristics with those discovered in other animals and plants, such as shorter exons and introns than mRNAs. Additionally, 79 and 73 DElncRNAs were screened from the workers' midguts at 7 dpi and 10 dpi, respectively, indicating the alteration of the overall expression pattern of lncRNAs in host midguts after N. ceranae infestation. These DElncRNAs could, respectively, regulate 87 and 73 upstream and downstream genes, involving a suite of functional terms and pathways, such as metabolic process and Hippo signaling pathway. Additionally, 235 and 209 genes co-expressed with DElncRNAs were found to enrich in 29 and 27 terms, as well as 112 and 123 pathways, such as ABC transporters and the cAMP signaling pathway. Further, it was detected that 79 (73) DElncRNAs in the host midguts at 7 (10) dpi could target 321 (313) DEmiRNAs and further target 3631 (3130) DEmRNAs. TCONS&#95;00024312 and XR&#95;001765805.1 were potential precursors for ame-miR-315 and ame-miR-927, while TCONS&#95;00006120 was the putative precursor for both ame-miR-87-1 and ame-miR-87-2. These results together suggested that DElncRNAs are likely to play regulatory roles in the host response to N. ceranae infestation through the regulation of neighboring genes via a cis -acting effect, modulation of co-expressed mRNAs via trans -acting effect, and control of downstream target genes' expression via competing endogenous RNA networks. Our findings provide a basis for disclosing the mechanism underlying DElncRNA-mediated host N. ceranae response and a new perspective into the interaction between A. c. cerana and N. ceranae .

Exosomes have the ability to carry a wide range of chemicals, convey them to target cells or target regions, and act as "messengers." For the purpose of investigating embryo attachment, it is helpful to comprehend the range of exosomal mRNAs and miRNAs derived from the uterine flushing fluid before and after embryo attachment. In this study, we recovered exosomes from goat uterine rinsing fluid at 5, 15, and 18 days of gestation and used RNA-Seq to identify the mRNA and miRNA profiles of exosomes obtained from uterine rinsing fluid before and after embryo implantation. In total, 91 differently expressed miRNAs and 27,487 differentially expressed mRNAs were found. The target genes predicted by the differentially expressed miRNAs and the differentially expressed mRNAs were mainly membrane-related organelles with catalytic activity, binding activity, transcriptional regulation activity, and involved in metabolism, biological regulation, development, and other processes. This was revealed by GO analysis. Furthermore, KEGG analysis revealed that they were abundant in signaling pathways associated with embryo implantation, including the "PI3K-Akt signaling pathway," "Toll-like receptor signaling pathway," "TGF-beta signaling route," "Notch signaling pathway," and others. Moreover, our research has demonstrated, for the first time, that chi-let-7b-5p specifically targets the 3'UTR of CXCL10. Our research offers a fresh viewpoint on the mechanics of embryo attachment.

Background: Cerebral ischemia/reperfusion (I/R) is a pathological process that occurs in ischemic stroke. Bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos) have been verified to relieve cerebral I/R-induced inflammatory injury. Hence, we intended to clarify the function of BMSC-Exos-delivered lncRNA KLF3-AS1 (BMSC-Exos KLF3-AS1) in neuroprotection and investigated its potential mechanism., Methods: To mimic cerebral I/R injury in vivo and in vitro, middle cerebral artery occlusion (MCAO) mice model and oxygen-glucose deprivation (OGD) BV-2 cell model were established. BMSC-Exos KLF3-AS1 were administered in MCAO mice or OGD-exposed cells. The modified neurological severity score (mNSS), shuttle box test, and cresyl violet staining were performed to measure the neuroprotective functions, while cell injury was evaluated with MTT, TUNEL and reactive oxygen species (ROS) assays. Targeted genes and proteins were detected using western blot, qRT-PCR, and immunohistochemistry. The molecular interactions were assessed using RNA immunoprecipitation, co-immunoprecipitation and luciferase assays., Results: BMSC-Exos KLF3-AS1 reduced cerebral infarction and improved neurological function in MCAO mice. Similarly, it also promoted cell viability, suppressed apoptosis, inflammatory injury and ROS production in cells exposed to OGD. BMSC-Exos KLF3-AS1 upregulated the decreased Sirt1 induced by cerebral I/R. Mechanistically, KLF3-AS1 inhibited the ubiquitination of Sirt1 protein through inducing USP22. Additionally, KLF3-AS1 sponged miR-206 to upregulate USP22 expression. Overexpression of miR-206 or silencing of Sirt1 abolished KLF3-AS1-mediated protective effects., Conclusion: BMSC-Exos KLF3-AS1 promoted the Sirt1 deubiquitinating to ameliorate cerebral I/R-induced inflammatory injury via KLF3-AS1/miR-206/USP22 network., (© 2023. The Author(s).)

Cognitive impairment is the main clinical feature following stroke, and microglia-mediated inflammatory response is a major contributor to it. Coreopsis tinctoria Nutt., an edible chrysanthemum, is commonly used as a functional ingredient in healthcare beverages and food. Okanin, the main active ingredient of Coreopsis tinctoria Nutt. flower, inhibits microglial activation. However, the role of okanin in cognitive impairment following ischemic stroke is still unknown. In this study, we investigated the effect of okanin on ischemic stroke and its underlying mechanism both in vivo and in vitro . Okanin was found to attenuate cognitive impairment in bilateral common carotid artery occlusion (BCCAO) mice, inhibit neuronal loss and microglial activation, decrease NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation, and increase miR-7 expression. Okanin suppressed NLRP3 inflammasome activation in oxygen-glucose deprivation (OGD) and lipopolysaccharide (LPS)-stimulated microglia by increasing miR-7 expression and inhibited microglia-induced neuronal injury. This study provides new insights into the role of okanin in ischemic stroke and shows that the miR-7/NLRP3 axis plays an important role in mediating the beneficial effects of okanin on cerebral ischemia. These findings suggest that okanin has great potential as a functional food for stroke recovery.

The long noncoding RNAs (lncRNAs) are widely involved in the progression of various malignant tumors. The current study investigated the role and mechanism of lncRNA melanoma highly expressed noncoding RNA (MHENCR) in colorectal carcinoma. The expression of MHENCR was measured by real-time quantitative reverse transcription PCR (RT-qPCR). The chi-square analysis was used to analyze the correlation between MHECNR and miR-532-3p. Kaplan-Meier curve and multivariate Cox regression analysis were conducted to assess the significance of MHENCR in clinic. The interaction of MHENCR and miR-532-3p was probed using Pearson analysis and dual-luciferase reporter assay. Cellular experiments were implemented to explore the effects of MHENCR/miR-532-3p on colorectal carcinoma cells. Compared with para-cancerous tissues, MHENCR expression was increased and miR-532-3p expression was decreased in tumor tissues. High expression of MHENCR exhibited shorter overall survival. Interfering of MHENCR suppressed cellular activities while the silence of miR-532-3p diminished the decreased cellular behaviors in colorectal carcinoma cells. Interfering with MHENCR expression represses colorectal carcinoma cell proliferation, migration, and invasion by regulating miR-532-3p. MHENCR may act as a novel prognostic marker in colorectal carcinoma and MHENCR/miR-532-3p may serve as a potential target for treating colorectal carcinoma.

CRISPR/Cas12a has shown great potential in molecular diagnostics, but its application in sensing of microRNAs (miRNAs) was limited by sensitivity and complexity. Here, we have sensitively and conveniently detected microRNAs by reasonably integrating metal-organic frameworks ( M OFs) based bio b arcodes with CRISPR/ C as12a a ssay (designated as MBCA). In this work, DNA-functionalized Zr-MOFs were designed as the converter to convert and amplify each miRNA target into activators that can initiate the trans -cleavage activity of CRISPR/Cas12a to further amplify the signal. Such integration provides a universal strategy for sensitive detection of miRNAs. By tuning the complementary sequences modified on nanoprobes, this assay achieves subattomolar sensitivity for different miRNAs and was selective to single-based mismatches. With the proposed method, the expression of miR-21 in different cancer cells can be assessed, and breast cancer patients and healthy individuals can be differentiated by analyzing the target miRNAs extracted from serum samples, holding great potential in clinical diagnosis.

Gastric cancer is a common malignant tumor in China; however, its carcinogenesis remains unknown. Focadhesin (FOCAD) is a tumor suppressor gene in gliomas, its expression, role, and mechanism in gastric cancer have not been defined. The aim of the present study was to explore the expression pattern of FOCAD in human normal tissues and cancer tissues and elucidate the role and regulatory mechanism of Early Growth Response 1 (EGR1) in FOCAD and its intron, miR-491-5p, in gastric cancer. Immuno histochemical staining revealed that FOCAD is widely and highly expressed in normal gastric mucosa, but is absent in gastric cancer tissue. Based on an association analysis FOCAD expression was found to be negatively associated with lymph node metastasis (P = 0.004); higher FOCAD levels were associated with longer survival in patients with gastric cancer (P = 0.001). MTT, colony, Transwell chamber, and flow cytometry assays revealed that siFOCAD promoted cell proliferation, growth, and migration, and inhibited apoptosis. Furthermore, bioinformatic analysis, Fluorescence reporter gene and chromatin immunoprecipitation analyses confirmed that EGR1 binds to the promoter and negatively regulates FOCAD and miR-491-5p at the transcriptional level. The overexpression of EGR1 was also found to promote cell proliferation, growth, and migration, and inhibit apoptosis. Overall, FOCAD is specifically overexpressed in the gastric mucosa and is significantly downregulated in gastric cancer. To our knowledge, this is the first study to demonstrate that FOCAD is a tumor suppressor, higher FOCAD levels might be a better prognostic marker of gastric cancer, and FOCAD/miR-491-5p may be negatively regulated by EGR1., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Multiple myeloma (MM) is a relatively common hematologic tumor, and the study of non-coding RNAs in MM is gradually increasing. Our study aimed to reveal the regulatory mechanism of circular RNA&#95;0003489 (circ&#95;0003489)/microRNA-433-3p (miR-433-3p)/Pre-B-cell leukemia homeobox 3 (PBX3) axis in MM., Methods: Circ&#95;0003489, miR-433-3p and PBX3 contents were measured by real-time quantitative PCR or western blot. Functionally, MM cell proliferation and apoptosis were evaluated using cell counting kit-8, flow cytometry and EdU assays. Interaction between miR-433-3p and circ&#95;0003489 or PBX3 was confirmed with the application of dual-luciferase reporter assay and RNA pull down assay., Results: Circ&#95;0003489 and PBX3 were upregulated, while miR-433-3p was downregulated in MM tissues. Circ&#95;0003489 knockdown or miR-433-3p overexpression remarkably suppressed MM proliferation and increased apoptosis in vitro . In terms of mechanism, circ&#95;0003489 could sponge miR-433-3p to regulate PBX3. Besides, miR-433-3p downregulation or PBX3 overexpression reversed the inhibition effect of circ&#95;0003489 knockdown on MM progression., Conclusion: Circ&#95;0003489 facilitated MM progression by targeting miR-433-3p/PBX3 axis, suggesting that it might be a potential target for MM.

Papillary thyroid carcinoma (PTC) is a common thyroid malignancy. Circular RNAs (circRNAs) have been implicated in the development of PTC. Here, we explored the function and mechanism of circRNA family with sequence similarity 53, member B (circ&#95;FAM53B) in PTC pathogenesis. Circ&#95;FAM53B, microRNA (miR)-183-5p and coiled-coil domain containing 6 (CCDC6) levels were gauged by quantitative reverse transcription polymerase chain reaction (qRT-PCR) or Western blotting. The direct relationship between miR-183-5p and circ&#95;FAM53B or CCDC6 was verified by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Our data showed that circ&#95;FAM53B expression was reduced in PTC tissues and cells. Circ&#95;FAM53B expression restrained proliferation, migration, and invasion and triggered apoptosis of PTC cells, as well as hindered HUVEC tube formation. Circ&#95;FAM53B repressed miR-183-5p expression. MiR-183-5p re-expression reversed the effects of circ&#95;FAM53B on cell behaviors. MiR-183-5p targeted and inhibited CCDC6, and circ&#95;FAM53B upregulated CCDC6 through miR-183-5p competition. MiR-183-5p knockdown repressed cell proliferation, migration, invasion, and tube formation and facilitated apoptosis by upregulating CCDC6. Furthermore, circ&#95;FAM53B reduced tumor growth in vivo. Collectively, our findings suggest that circ&#95;FAM53B affects PTC cell biological behaviors via the miR-183-5p-CCDC6 axis., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Synergism between avian leukosis virus subgroup J (ALV-J) and reticuloendotheliosis virus (REV) has been reported frequently in co-infected chicken flocks. Although significant progress has been made in understanding the tumorigenesis mechanisms of ALV and REV, how these two simple oncogenic retroviruses induce synergistic oncogenicity remains unclear. In this study, we found that ALV-J and REV synergistically promoted mutual replication, suppressed cellular senescence, and activated epithelial-mesenchymal transition (EMT) in vitro. Mechanistically, structural proteins from ALV-J and REV synergistically activated the expression of Musashi-1(MSI1), which directly targeted pri-miR-147 through its RNA binding site. This inhibited the maturation of miR-147, which relieved the inhibition of NF-κB/KIAA1199/EGFR signaling, thereby suppressing cellular senescence and activating EMT. We revealed a synergistic oncogenicity mechanism induced by ALV-J and REV in vitro. The elucidation of the synergistic oncogenicity of these two simple retroviruses could help in understanding the mechanism of tumorigenesis in ALV-J and REV co-infection and help identify promising molecular targets and key obstacles for the joint control of ALV-J and REV and the development of clinical technologies.

Breast cancer (BC) has been a serious threat to women's health. Exosomes contain a variety of biomolecules, which is an excellent choice as disease diagnostic markers, but whether it could be applied as a noninvasive biomarker for BC diagnosis demands to be additional studied. In this study, we aimed at creating a predictive model and reveal the value of plasma exosomal miRNA (exo-miRNA) in early diagnosis of BC. Firstly, exosomes isolated from plasma were identified by Nanoparticle Tracking Analysis (NTA), Transmission Electron Microscope (TEM), and Western Blot. miRNA expression in plasma samples from 56 BC patients and 40 normal controls was analyzed by high-throughput sequencing. miRNAs with strong correlation characteristics were selected by Lasso logistic regression. Then, we built the training set and test set, evaluated the Lasso regression accuracy, and evaluated the performance of different models in the training set and test set. Finally, GO analysis, KEGG, and Reactome pathway enrichment analysis were used to understand the biological significance of 16 characteristic miRNAs. The successful separation of exosomes in serum was identified by NTA, TEM, and Western Blot. The training set data matrix containing 1962 miRNAs was obtained by sequencing for model construction, and 16 strongly correlated miRNAs were selected by Lasso logistic regression. The accuracy of Lasso regression in training set and test set were 97.22% and 95.83%, respectively. We built different models and evaluated the performance of each model in the training set and test set. The results showed that the AUC values of Lasso, SVM, GBDT, and Random Forest model in the training set were 1, and the AUC values in the test set were 0.979, 0.936, 0.971, and 0.979, respectively. Bioinformatics analysis showed that 16 signature miRNAs were significantly enriched in cancer-related pathways such as herpes simplex virus 1 infection, TGF- β signaling, and Toll-like receptor family. The results of this study suggest that the 16 characteristic miRNAs screened from plasma exosomes can be used as a group of biomarkers, and the prediction model constructed based on this set of markers is expected to be used in the early diagnosis of BC., Competing Interests: All authors declare that there is no conflict of interest., (Copyright © 2022 Yangyang Pan et al.)

Breast cancer is quite a prevalent cancer worldwide, and it is the leading cause of cancer-related deaths among female populations worldwide. Increasingly more efforts have been made in exploration of circular RNA functions in various malignancies. In this study, the primary target was to verify the putative influences of circ&#95;0041732 on breast cancer progression and the corresponding regulatory mechanism. In addition to measurement of RNAs and proteins, functional assays were done to examine the changes in cell proliferation and cell cycle, and the potential association among genes was investigated by mechanism assays. According to experimental results, significant upregulation of circ&#95;0041732 was confirmed in breast cancer tissues and cell lines. E2F4 was proved to transcriptionally modulate circ&#95;0041732. Moreover, circ&#95;0041732 was validated to accelerate breast cancer cell proliferation and impede G2-M arrest and cell apoptosis, and the oncogenic role of circ&#95;0041732 in breast cancer was further verified via in vivo experiments. circ&#95;0041732 could sponge miR-541-3p to enhance expression levels of RelA and GLI4, thus activating NFκB and Hedgehog pathways and affecting breast cancer cell proliferation, cell cycle, and apoptosis. In all, E2F4-mediated circ&#95;0041732 could activate RelA/NFκB and GLI4/Hedgehog signaling pathways via modulation on miR-541-3p/RelA/GLI4 to promote breast cancer progression., Implications: E2F4-mediated circ&#95;0041732 upregulation resulted in the activation of NFκB and Hedgehog pathways via sponging miR-541-3p and enhancing expression levels of RelA and GLI4, thus affecting breast cancer cell proliferation, cell cycle, and cell apoptosis., (©2022 American Association for Cancer Research.)

Hypertensive disorders in pregnancy (HDIP) represent one of the leading causes of maternal and perinatal mortality. microRNA (miR)-25-3p plays roles in HDIP diagnosis. We explored miR-25-3p clinical roles in HDIP. HDIP patients [gestation hypertension (GH), mild preeclampsia (mPE), and severe preeclampsia (sPEz)], and normal pregnant women serving as the control were enrolled. Serum miR-25-3p expression patterns were detected by RT-qPCR. The diagnostic efficacy of miR-25-3p on HDIP was analyzed with a ROC curve. Patients were assigned to the high/low miR-25-3p expression groups according to the median value of miR-25-3p expression. All patients were followed up until delivery, and gestational weeks and pregnancy outcomes were recorded at delivery. The effects of miR-25-3p expression on pregnancy outcomes of GH, mPE, and sPEz patients were analyzed by Kaplan-Meier. miR-25-3p expression in GH, mPE, and sPEz patients was up-regulated. In sPEz patients, systolic and diastolic blood pressure, 24-h urine protein, AST, ALT, GGT, and SCr were increased, and PLT was decreased in the high expression group. High miR-25-3p expression was associated with an increased risk of adverse pregnancy outcomes in PE patients. Collectively, high miR-25-3p expression could aid HDIP diagnosis, and associated with an increased risk of adverse pregnancy outcomes in PE patients.

Non-small cell lung carcinoma (NSCLC) is an aggressive malignant tumor. Growing evidences have revealed that circular RNA (circRNA) is involved in NSCLC progression. This study aims to investigate the role of circular RNA F-box and WD repeat domain containing 8 (circFBXW8) in NSCLC progression and the underlying mechanism. The expression of circFBXW8, microRNA-370-3p (miR-370-3p) and tripartite motif containing 44 (TRIM44) mRNA was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Protein expression was detected by western blot analysis or immunohistochemistry assay. Additionally, cell viability, colony-forming ability, proliferation and apoptosis were investigated by 3-(4,5-Dimethylthazol-2-yl)-2,5-diphenyltetrazolium bromide, cell colony formation, 5-Ethynyl-29-deoxyuridine and flow cytometry analysis assays, respectively. Cell migratory and invasive abilities were examined by wound-healing and transwell assays. The regulatory relationship between miR-370-3p and circFBXW8 or TRIM44 was identified by dual-luciferase reporter and RNA pull-down assays. Furthermore, xenograft experiment was employed to explain the effect of circFBXW8 silencing on tumor formation. CircFBXW8 and TRIM44 expression were upregulated, while miR-370-3p was downregulated in NSCLC tissues, cells and the exosomes from NSCLC cells compared with respective controls. CircFBXW8 depletion repressed NSCLC cell proliferation, migration and invasion, but promoted cell apoptosis. CircFBXW8 acted as a sponge of miR-370-3p and regulated NSCLC cell malignancy by binding to miR-370-3p. Additionally, miR-370-3p repressed NSCLC cell processes by regulating TRIM44. CircFBXW8 knockdown inhibited tumor formation in vivo. Further, circFBXW8 secretion was mediated by exosomes. CircFBXW8 modulated NSCLC progression by increasing TRIM44 expression through sponging miR-370-3p, which provided a new direction for studying the therapy of NSCLC., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Preeclampsia (PE), the most significant adverse exposure to cardiovascular risk during pregnancy, is one of the three major factors contributing to maternal and fetal mortality and the leading cause of preterm birth. Recently, various miRNAs have been reported to participate in PE occurrence and development. Nevertheless, the regulatory impact of miR-195-5p in PE is still indistinct., Methods: Quantitative realtime-PCR (qRT-PCR), western blot, and fluorescence in situ hybridization (FISH) assay were performed to examine miR-195-5p and FGF2 expressions in PE serum samples or HTR-8/SVneo and TEV-1 cells. CCK8, flow cytometry, wound scratch, and transwell assays were conducted to determine cell viability, cycle, apoptosis, migration, and invasion. Dual-luciferase reporter assay unveiled the relationship between miR-195-5p and FGF2. Migration-related and invasion-related protein expressions were measured by western blot assay., Results: miR-195-5p was prominently downregulated while FGF2 was increased in serum samples from PE patients and hypoxia-treated human trophoblast cells. FGF2 was predicted as a downstream target of miR-195-5p and targeted association was verified by dual-luciferase reporter assay. Functional experiments elaborated that miR-195-5p could facilitate trophoblast cell proliferation and metastasis but hinder cell cycle and apoptosis. Inversely, overexpressing of FGF2 could reverse the effects of miR-195-5p on trophoblast cell growth., Discussion: miR-195-5p was decreased in PE serum samples and cell lines, serving as a potential biomarker in protecting PE exacerbation by targeting FGF2., (© 2022 Japan Society of Obstetrics and Gynecology.)

The functional role of microRNA-375 (miR-375) in the development of prostate cancer (PCa) remains controversial. Previously, we found that plasma exosomal miR-375 is significantly elevated in castration-resistant PCa (CRPC) patients compared with castration-sensitive PCa patients. Here, we aimed to determine how miR-375 modulates CRPC progression and thereafter to evaluate the therapeutic potential of human umbilical cord mesenchymal stem cell (hucMSC)-derived exosomes loaded with miR-375 antisense oligonucleotides (e-375i). We used miRNA in situ hybridization technique to evaluate miR-375 expression in PCa tissues, gain- and loss-of-function experiments to determine miR-375 function, and bioinformatic methods, dual-luciferase reporter assay, qPCR, IHC and western blotting to determine and validate the target as well as the effects of miR-375 at the molecular level. Then, e-375i complexes were assessed for their antagonizing effects against miR-375. We found that the expression of miR-375 was elevated in PCa tissues and cancer exosomes, correlating with the Gleason score. Forced expression of miR-375 enhanced the expression of EMT markers and AR but suppressed apoptosis markers, leading to enhanced proliferation, migration, invasion, and enzalutamide resistance and decreased apoptosis of PCa cells. These effects could be reversed by miR-375 silencing. Mechanistically, miR-375 directly interfered with the expression of phosphatase nonreceptor type 4 (PTPN4), which in turn stabilized phosphorylated STAT3. Application of e-375i could inhibit miR-375, upregulate PTPN4 and downregulate p-STAT3, eventually repressing the growth of PCa. Collectively, we identified a novel miR-375 target, PTPN4, that functions upstream of STAT3, and targeting miR-375 may be an alternative therapeutic for PCa, especially for CRPC with high AR levels., (© 2022. The Author(s).)

Circular RNAs have been confirmed to play vital roles in the development of human diseases. Nevertheless, their effects on modulating mesenchymal stromal cells (MSCs) to heal diabetic wounds are still elusive. In this study, our data revealed that MSCs treated with high glucose displayed an evident reduction in circARHGAP12 expression, whereas autophagy mediated by circARHGAP12 suppressed high glucose-triggered apoptosis of MSCs. Mechanistically, circARHGAP12 was capable of directly interacting with miR-301b-3p and subsequently sponged microRNA to modulate the expression of the miR-301b-3p target genes ATG16L1 and ULK2 and the downstream signaling pathway. Moreover, circARHGAP12 promoted the survival of MSCs in diabetic wounds in vivo and accelerated wound healing. Collectively, these results suggest that circARHGAP12/miR-301b-3p/ATG16L1 and circARHGAP12/miR-301b-3p/ULK2 regulatory networks might be an underlying therapeutic target for MSCs in diabetic wound healing., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Myocardial ischemia-reperfusion (MIR) injury is a common stimulus for cardiac diseases like cardiac arrhythmias and heart failure and may cause high mortality rates. Salviae miltiorrhizae liguspyragine hydrochloride and glucose injection (SGI) has been widely used to treat myocardial and cerebral infarctions in China even though its pharmacological mechanisms are not completely clear., Methods: The protective effect and mechanism of SGI on MIR injury and heart failure were investigated through the H9c2 cell model induced by hypoxia/reoxygenation (H/R) and rapamycin, zebrafish model induced by H/R and isoprenaline, and rat MIR model., Results: SGI significantly reduced the infarct size and alleviated the impairment of cardiac functions in the MIR rat model and H/R zebrafish model and promoted cell viability of cardiomyocyte-like H9c2 cells under H/R condition. Consistently, SGI significantly downregulated the serum level of biomarkers for cardiac damage and attenuated the oxidative damage in the MIR and H/R models. We also found that SGI could downregulate the increased autophagy level in those MIR and H/R models since autophagy can contribute to the injurious effects of ischemia-reperfusion in the heart, suggesting that SGI may alleviate MIR injury via regulating the autophagy pathway. In addition, we demonstrated that SGI also played a protective role in the isoproterenol-induced zebrafish heart failure model, and SGI significantly downregulated the increased autophagy and SP1/GATA4 pathways., Conclusion: SGI may exert anti-MIR and heart failure by inhibiting activated autophagy and the SP1/GATA4 pathway., Competing Interests: The authors declare no competing interests., (Copyright © 2022 Shang Kong et al.)