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Abstract Background CSLCs(Cancer stem cell-like cells), which are central to tumorigenesis, are intrinsically influenced by epigenetic modifications. This study aimed to elucidate the underlying mechanism involving the DNMT1/miR-152-3p/SOS1 axis in regulating the self-renewal and tumor growth of LCSLCs (lung cancer stem-like cells). Materials and methods Target genes of miR-152-3p were predicted using TargetScan Human 8.0. Self-renewal and tumor growth of LCSLC were compared in suspension-cultured non-small cell lung cancer (NSCLC) cell lines H460 and A549 cell-derived globe cells. Functional effects of the DNMT1/miR-152-3p/SOS1 axis were assessed through gain-of-function experiments in vitro and in vivo. Additionally, luciferase reporter assays were employed to analyze the interaction among DNMT1, miR-152-3p, and SOS1. Results Our findings highlight a negative interaction between DNMT1 and miR-152-3p, resulting in reduced miR-152-3p level. This, in turn, leads to the alleviation of the inhibitory effect of miR-152-3p on the target gene SOS1, ultimately activating SOS1 and playing an essential role in self-renewal and tumor growth of LCSLC. However, the alteration of SOS1 does not affect DNMT1/miR-152-3p regulation. Therefore, it is reasonable to infer that the DNMT1/miR-152-3p negative feedback loop critically sustains self-renewal and tumor growth of LCSLC through SOS1. Conclusions This study reveals a novel mechanism underpinning self-renewal and tumor growth of CSLC (cancer stem cell) in NSCLC and identifies potential therapeutic targets for NSCLC treatment.

The objective of this study was to investigate the mechanism of curcumin in diabetic foot ulcer (DFU) wound healing. A DFU rat model was established, and fibroblasts were cultured in a high-glucose (HG) environment to create a cell model. Various techniques, including Western blot, RT‒qPCR, flow cytometry, Transwell, cell scratch test and H&E staining, were employed to measure the levels of relevant genes and proteins, as well as to assess cell proliferation, apoptosis, migration, and pathological changes. The results showed that miR-152-3p was overexpressed in DFU patients, while FBN1 was underexpressed. Curcumin was found to inhibit fibroblast apoptosis, promote proliferation, migration, and angiogenesis in DFU rats, and accelerate wound healing in DFU rats. In addition, overexpression of miR-152-3p weakened the therapeutic effect of curcumin, while overexpression of FBN1 reversed the effects of the miR-152-3p mimic. Further investigations into the underlying mechanisms revealed that curcumin expedited wound healing in DFU rats by restoring the FBN1/TGF-β pathway through the inhibition of miR-152-3p. In conclusion, curcumin can suppress the activity of miR-152-3p, which, in turn, leads to the rejuvenation of the FBN1/TGF-β pathway and accelerates DFU wound healing. [ABSTRACT FROM AUTHOR]

Background: CSLCs(Cancer stem cell-like cells), which are central to tumorigenesis, are intrinsically influenced by epigenetic modifications. This study aimed to elucidate the underlying mechanism involving the DNMT1/miR-152-3p/SOS1 axis in regulating the self-renewal and tumor growth of LCSLCs (lung cancer stem-like cells). Materials and methods: Target genes of miR-152-3p were predicted using TargetScan Human 8.0. Self-renewal and tumor growth of LCSLC were compared in suspension-cultured non-small cell lung cancer (NSCLC) cell lines H460 and A549 cell-derived globe cells. Functional effects of the DNMT1/miR-152-3p/SOS1 axis were assessed through gain-of-function experiments in vitro and in vivo. Additionally, luciferase reporter assays were employed to analyze the interaction among DNMT1, miR-152-3p, and SOS1. Results: Our findings highlight a negative interaction between DNMT1 and miR-152-3p, resulting in reduced miR-152-3p level. This, in turn, leads to the alleviation of the inhibitory effect of miR-152-3p on the target gene SOS1, ultimately activating SOS1 and playing an essential role in self-renewal and tumor growth of LCSLC. However, the alteration of SOS1 does not affect DNMT1/miR-152-3p regulation. Therefore, it is reasonable to infer that the DNMT1/miR-152-3p negative feedback loop critically sustains self-renewal and tumor growth of LCSLC through SOS1. Conclusions: This study reveals a novel mechanism underpinning self-renewal and tumor growth of CSLC (cancer stem cell) in NSCLC and identifies potential therapeutic targets for NSCLC treatment. [ABSTRACT FROM AUTHOR]

Abstract Background Radiotherapy is widely used in treating cervical cancer patients, however, radioresistance unavoidably occurs and seriously affects the treatment effect. It is well known that hypoxia plays an important role in promoting radioresistance in tumor microenvironment, yet our understanding of the effect of small extracellular vesicles miRNA on cervical cancer radiosensitivity in hypoxic environment is still limited. Methods Small extracellular vesicles extracted from hypoxic and normoxic cultured cervical cancer cells were evaluated for their effects on radioresistance. miR-152-3p was found to be a potential effector in hypoxia-derived extracellular vesicles by searching the GEO database. Its downstream substrate was confirmed by double luciferase report, which was KLF15. The role of miR-152-3p and KLF15 in regulating cervical cancer radioresistance was detected by cell activity assays. The findings were confirmed in vivo by animal models. The expression of miR-152-3p was quantified by qRT-PCR and its prognostic significance was evaluated. Results Hypoxic environment promoted the secretion of small extracellular vesicles, and reduced the apoptosis and DNA damage caused by radiation, accompanied by increased expression of small extracellular vesicles miR-152-3p from hypoxic cervical cancer cells. Furthermore, small extracellular vesicles miR-152-3p promoted Hela xenograft growth and reduced the radiosensitivity vivo. Mechanism studies revealed that KLF15 protein was the downstream target of miR-152-3p in regulating radioresistance. Conclusion Our findings suggest that small extracellular vesicles miR-152-3p affects the therapeutic effect of radiotherapy and holds potential as a biomarker or therapeutic target for cervical cancer prognosis and improving radiotherapy.

Müller cells play a critical role in the closure of macular holes, and their proliferation and migration are facilitated by the internal limiting membrane (ILM). Despite the importance of this process, the underlying molecular mechanism remains underexplored. This study investigated the effects of ILM components on the microRNA (miRNA) profile of Müller cells. Rat Müller cells (rMC-1) were cultured with a culture insert and varying concentrations of ILM component coatings, namely, collagen IV, laminin, and fibronectin, and cell migration was assessed by measuring cell-free areas in successive photographs following insert removal. MiRNAs were then extracted from these cells and analyzed. Mimics and inhibitors of miRNA candidates were transfected into Müller cells, and a cell migration assay and additional cell viability assays were performed. The results revealed that the ILM components promoted Müller cell migration (p < 0.01). Among the miRNA candidates, miR-194-3p was upregulated, whereas miR-125b-1-3p, miR-132-3p, miR-146b-5p, miR-152-3p, miR-196a-5p, miR-542-5p, miR-871-3p, miR-1839-5p, and miR-3573-3p were significantly downregulated (p < 0.05; fold change > 1.5). Moreover, miR-152-3p and miR-196a-5p reduced cell migration (p < 0.05) and proliferation (p < 0.001), and their suppressive effects were reversed by their respective inhibitors. In conclusion, miRNAs were regulated in ILM component-activated Müller cells, with miR-152-3p and miR-196a-5p regulating Müller cell migration and proliferation. These results serve as a basis for understanding the molecular healing process of macular holes and identifying potential new target genes in future research. [ABSTRACT FROM AUTHOR]

Background: Radiotherapy is widely used in treating cervical cancer patients, however, radioresistance unavoidably occurs and seriously affects the treatment effect. It is well known that hypoxia plays an important role in promoting radioresistance in tumor microenvironment, yet our understanding of the effect of small extracellular vesicles miRNA on cervical cancer radiosensitivity in hypoxic environment is still limited. Methods: Small extracellular vesicles extracted from hypoxic and normoxic cultured cervical cancer cells were evaluated for their effects on radioresistance. miR-152-3p was found to be a potential effector in hypoxia-derived extracellular vesicles by searching the GEO database. Its downstream substrate was confirmed by double luciferase report, which was KLF15. The role of miR-152-3p and KLF15 in regulating cervical cancer radioresistance was detected by cell activity assays. The findings were confirmed in vivo by animal models. The expression of miR-152-3p was quantified by qRT-PCR and its prognostic significance was evaluated. Results: Hypoxic environment promoted the secretion of small extracellular vesicles, and reduced the apoptosis and DNA damage caused by radiation, accompanied by increased expression of small extracellular vesicles miR-152-3p from hypoxic cervical cancer cells. Furthermore, small extracellular vesicles miR-152-3p promoted Hela xenograft growth and reduced the radiosensitivity vivo. Mechanism studies revealed that KLF15 protein was the downstream target of miR-152-3p in regulating radioresistance. Conclusion: Our findings suggest that small extracellular vesicles miR-152-3p affects the therapeutic effect of radiotherapy and holds potential as a biomarker or therapeutic target for cervical cancer prognosis and improving radiotherapy. [ABSTRACT FROM AUTHOR]

Evodiamine (EVO) has been demonstrated to promote apoptosis of ovarian cancer cells, and upregulate miR‐152‐3p level in colorectal cancer. Here, we explore part of the network mechanism of EVO and miR‐152‐3p in ovarian cancer. The bioinformatics website, dual luciferase reporter assay, and quantitative real‐time polymerase chain reaction were applied to analyze the network among EVO, lncRNA, miR‐152‐3p, and mRNA. The effect and mechanism of EVO on ovarian cancer cells were determined using cell counting kit‐8, flow cytometry, TUNEL, Western blot, and rescue experiments. As a result, EVO dose‐dependently attenuated cell viability, induced G2/M phase arrest and apoptosis, promoted miR‐152‐3p level (4.5‐ or 2‐fold changes), and inhibited expressions of NEAT1 (0.225‐ or 0.367‐fold changes), CDK8 (0.625‐ or 0.571‐fold changes), and CDK19 (0.25‐ or 0.147‐fold changes) in OVCAR‐3 and SKOV‐3 cells. In addition, EVO decreased Bcl‐2 expression, but increased the expressions of Bax and c‐caspase‐3. NEAT1 targeted miR‐152‐3p which bound to CDK19. The impacts of EVO on cell viability, cycle, apoptosis, and apoptosis‐related proteins were partially reversed by miR‐152‐3p inhibitor, NEAT1 overexpression, or CDK19 overexpression. Furthermore, miR‐152‐3p mimic offset the effects of NEAT1 or CDK19 overexpression. The role of NEAT1 overexpression in the biological phenotype of ovarian cancer cells was counteracted by shCDK19. In conclusion, EVO attenuates ovarian cancer cell progression via the NEAT1‐miR‐152‐3p‐CDK19 axis. [ABSTRACT FROM AUTHOR]

Background: Bone marrow mesenchymal stem cells (BMSCs) can differentiate into osteoblasts and thus present a tremendous therapeutic potential in osteoporosis. Here, we elucidated the involvement of long non-coding RNAs (lncRNAs) HOXA transcript antisense RNA, myeloid-specific 1 (HOTAIRM1) in the osteogenic differentiation of BMSCs. Methods and results: The expression levels of HOTAIRM1, miR-152-3p, ETS proto-oncogene 1 (ETS1), runt-related transcription factor 2 (RUNX2), Osterix, and osteocalcin (OCN) were determined by a quantitative real-time polymerase chain reaction (qRT-PCR) or western blot method. Targeted relationship between miR-152-3p and HOTAIRM1 or ETS1 was confirmed by dual-luciferase reporter and RNA pull-down assays. The activity of alkaline phosphatase (ALP) was measured by the ALP Activity Assay Kit. The extent of the calcium deposition was assessed by Alizarin Red Staining. Our data showed that HOTAIRM1 and ETS1 levels were up-regulated and miR-152-3p expression was down-regulated during osteogenic differentiation of human BMSCs (HBMSCs). HOTAIRM1 overexpression enhanced osteogenic differentiation of HBMSCs, and decreased level of HOTAIRM1 suppressed osteogenic differentiation of HBMSCs. HOTAIRM1 directly targeted miR-152-3p. ETS1 was identified as a direct and functional target of miR-152-3p. Furthermore, HOTAIRM1 functioned as a post-transcriptional regulator of ETS1 expression by miR-152-3p. Conclusion: The findings in this paper identify HOTAIRM1 as a novel regulator of osteogenic differentiation of BMSCs by the regulation of miR-152-3p/ETS1 axis, uncovering HOTAIRM1 as a promising therapeutic strategy for osteoporosis. [ABSTRACT FROM AUTHOR]

Resistance to chemotherapeutic drugs limits the efficacy of chemotherapy in non–small cell lung cancer (NSCLC). Autophagy is an essential mechanism which involves in drug resistance. Our previous research has revealed that miR‐152‐3p represses NSCLC progression. However, the mechanism of miR‐152‐3p in autophagy‐mediated chemoresistance in NSCLC remains unclear. Cisplatin‐resistant cell lines (A549/DDP and H446/DDP) were transfected with related vectors and subjected to cisplatin, autophagy inhibitor, activator, or extracellular signal–regulated kinase (ERK) activator. Flow cytometry, CCK8 and colony formation assays were performed for testing apoptosis and cell viability. The related RNAs or proteins were detected by qRT‐PCR or Western blot. Chromatin immunoprecipitation, luciferase reporter assay or RNA immunoprecipitation were used for validating the interaction between miR‐152‐3p and ELF1 or NCAM1. Co‐IP verified the binding between NCAM1 and ERK. The role of miR‐152‐3p in cisplatin resistance of NSCLC was also validated in vivo. The results showed that miR‐152‐3p and ELF1 were decreased in NSCLC tissues. miR‐152‐3p reversed cisplatin resistance by inhibiting autophagy through NCAM1. NCAM1 promoted autophagy through the ERK pathway and facilitated cisplatin resistance. ELF1 positively regulated miR‐152‐3p level by directly interacting with miR‐152‐3p promoter. miR‐152‐3p targeted NCAM1 to regulate NCAM1 level and then affected the binding of NCAM1 to ERK1/2. ELF1 inhibited autophagy and reversed cisplatin resistance through miR‐152‐3p/NCAM1. miR‐152‐3p inhibited autophagy and cisplatin resistance of xenograft tumor in mice. In conclusion, our study revealed that ELF1 inhibited autophagy to attenuate cisplatin resistance through the miR‐152‐3p/NCAM1/ERK pathway in H446/DDP and A549/DDP cells, suggesting a potential novel treatment strategy for NSCLC. [ABSTRACT FROM AUTHOR]

Purpose: Acute kidney injury (AKI) induced by renal ischaemia/reperfusion (I/R) during renal transplantation has been reported to be linked to the regulation of SIRT2, one of the members of SIRTUINS family. Current work is attempted to explore the influence and mechanism of SIRT7 in renal cell apoptosis controlled by miR-152-3p during renal I/R injury. Methods: Three databases were used to select the miRNAs regulating the expression of SIRT7. Overexpression and inhibition of miR-152-3p and Luciferase assay were employed to certify the modulation of miR-152-3p to SIRT7 in cells. RT-qPCR assay was used to measure the mRNA levels. Western blot assay was employed to determine the expression of proteins. TUNEL assay and Flow Cytometry were conducted to analyze cell apoptosis. Results: SIRT7 expression decreased in tissues of AKI patients and rats underwent renal I/R, which was associated with enhanced impairment of renal function. SIRT7 downregulation was attributed to the direct inhibition by miR-152-3p due to binding and inhibiting its seed sequence in 3′-UTR of SIRT7 mRNA. Consequently, the upregulation of miR-152-3p led to an inhibition of SIRT7 expression, an increase in expression of extrinsic apoptosis molecules containing FOXO3a, Bim, and caspase3, and apoptotic renal cells; while miR-152-3p inhibition abolished these phenotypes. Conclusion: SIRT7 downregulation by miR-152-3p is a leading cause of renal cell apoptosis and functional impairment induced by renal I/R. Inhibition of miR-152-3p to restore SIRT7 expression can be a promising strategy against renal I/R injury. [ABSTRACT FROM AUTHOR]

Müller cells play a critical role in the closure of macular holes, and their proliferation and migration are facilitated by the internal limiting membrane (ILM). Despite the importance of this process, the underlying molecular mechanism remains underexplored. This study investigated the effects of ILM components on the microRNA (miRNA) profile of Müller cells. Rat Müller cells (rMC-1) were cultured with a culture insert and varying concentrations of ILM component coatings, namely, collagen IV, laminin, and fibronectin, and cell migration was assessed by measuring cell-free areas in successive photographs following insert removal. MiRNAs were then extracted from these cells and analyzed. Mimics and inhibitors of miRNA candidates were transfected into Müller cells, and a cell migration assay and additional cell viability assays were performed. The results revealed that the ILM components promoted Müller cell migration (p < 0.01). Among the miRNA candidates, miR-194-3p was upregulated, whereas miR-125b-1-3p, miR-132-3p, miR-146b-5p, miR-152-3p, miR-196a-5p, miR-542-5p, miR-871-3p, miR-1839-5p, and miR-3573-3p were significantly downregulated (p < 0.05; fold change > 1.5). Moreover, miR-152-3p and miR-196a-5p reduced cell migration (p < 0.05) and proliferation (p < 0.001), and their suppressive effects were reversed by their respective inhibitors. In conclusion, miRNAs were regulated in ILM component-activated Müller cells, with miR-152-3p and miR-196a-5p regulating Müller cell migration and proliferation. These results serve as a basis for understanding the molecular healing process of macular holes and identifying potential new target genes in future research.

Abstract Background miR-152-3p functions as a tumour suppressor in the progression of hepatic tumorigenesis. Herein, we further discussed the prognostic significance and immune infiltration of miR-152-3p and its potential gene target in hepatocellular carcinoma (HCC). Methods The Cancer Genome Atlas (TCGA), Integrative Molecular Database of Hepatocellular Carcinoma (HCCDB), Human Protein Atlas (HPA) and Kaplan–Meier Plotter databases were used to evaluate miR-152-3p and roundabout guidance receptor 1 (ROBO1) expression, prognosis and immune infiltration. In vitro cell experiments, including cell proliferation and apoptosis, were evaluated using Cell Counting Kit 8 (CCK8) and terminal-deoxynucleotidyl transferase-mediated nick end labelling (TUNEL) assays. Results Up-regulation of ROBO1 functioned as an oncogene associated with poor prognosis, immune cell enrichment and cell proliferation in HCC. ROBO1 was significantly positively correlated with the enrichment of multiple immune cells and their biomarkers. Enrichment of type-2 T-helper (Th2) cells is an unfavourable biomarker of HCC prognosis. GSEA revealed that ROBO1 correlated with apoptosis, mitosis and carcinogenic signalling pathways. Suppression of cell proliferation and the enhancement of cell apoptosis by miR-152-3p mimics were counteracted by overexpression of ROBO1 in HCC cells. Conclusion ROBO1 expression is positively correlated with multiple immune checkpoint molecules, suggesting that ROBO1 may be a potential drug target to enhance the potency of immunotherapy. The miR-152-3p/ROBO1 signalling axis contributes to malignant progression and provides a prospective immunotherapeutic target for HCC.

Abstract In recent years, morbidity and mortality of prostate cancer (PCa) have increased dramatically, while mechanistic understanding of its onset and progression remains unmet. LncRNA SNHG3 has been proved to stimulate malignant progression of multiple cancers, whereas its functional mechanism in PCa needs to be deciphered. In this study, our analysis in the TCGA database revealed high SNHG3 expression in PCa tissue. Further analysis in starBase, TargetScan, and mirDIP databases identified the SNHG3/miR-152-3p/SLC7A11 regulatory axis. FISH was conducted to assess the distribution of SNHG3 in PCa tissue. Dual-luciferase reporter gene and RIP assays confirmed the relationship among the three objects. Next, qRT-PCR and western blot were conducted to measure expression levels of SNHG3, miR-152-3p, and SLC7A11. CCK-8, colony formation, Transwell, and flow cytometry were carried out to assess proliferation, migration, invasion, methionine dependence, apoptosis, and the cell cycle. It was noted that SNHG3 as a molecular sponge of miR-152-3p stimulated proliferation, migration, and invasion, restrained methionine dependence and apoptosis, and affected the cell cycle of PCa cells via targeting SLC7A11. Additionally, we constructed xenograft tumor models in nude mice and confirmed that knockdown of SNHG3 could restrain PCa tumor growth and elevate methionine dependence in vivo. In conclusion, our investigation improved understanding of the molecular mechanism of SNHG3 modulating PCa progression, thereby generating novel insights into clinical therapy for PCa.

Wang M, Wu Q, Fang M, Huang W, Zhu H. Onco Targets Ther. 2019;12:9513–9525. We, the Editor and Publisher of Onco Targets and Therapy are retracting the published article. Since publication, concerns have been raised about the integrity of the data in the article. When approached for an explanation, the authors have been unable to address the concerns raised and have not been able to provide sufficient supporting information. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article. The authors listed in this publication have been informed. We have been informed in our decision-making by our editorial policies and the COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Acute lung injury (ALI) is an early complication of sepsis and it is also considered as an important cause of high mortality in sepsis patients. This research aimed to explore the potential role and mechanism of long non-coding RNA (lncRNA) cancer susceptibility candidate 2 (CASC2) in sepsis-induced ALI. The levels of CASC2, microRNA-152-3p (miR-152-3p) and pyruvate dehydrogenase kinase 4 (PDK4) in sepsis patients and LPS-treated HPAEpiC were detected by quantitative real-time PCR and western blot. Cell viability and apoptosis were assessed by Counting Kit-8 (CCK-8) assay and flow cytometry. The concentrations of inflammatory factors were tested by Enzyme-linked immunosorbent assay. Oxidative stress was evaluated by the levels of reactive oxygen species and superoxide dismutase using corresponding commercial kits. The targeting relationship between miR-152-3p and CASC2 or PDK4 was verified by dual-luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull-down assays. CASC2 and PDK4 were down-regulated, while miR-152-3p was up-regulated in sepsis patients and LPS-stimulated HPAEpiC. Overexpression of CASC2 relieved the LPS-resulted cell viability inhibition, apoptosis promotion, inflammatory and oxidative damages in HPAEpiC. In addition, miR-152-3p was a miRNA target of CASC2 and CASC2 alleviated cell injury in LPS-disposed HPAEpiC by sponging miR-152-3p. Moreover, miR-152-3p directly targeted PDK4 and CASC2 increased the PDK4 expression by depending on the sponge effect on miR-152-3p. Meanwhile, inhibition of miR-152-3p attenuated LPS-triggered HPAEpiC injury by upregulating the level of PDK4. These results suggested that CASC2 ameliorated the LPS-induced injury in HPAEpiC via regulating miR-152-3p/PDK4 pathway. [ABSTRACT FROM AUTHOR]

Background: Cervical cancer ranks the fourth most prevalent type of cancer worldwide, characterized by a notably low survival rate, particularly in its metastatic stage. Despite 5-aminolevulinic acid photodynamic therapy (ALA-PDT) demonstrating potential anti-tumor effects against cervical cancer, the intricate mechanisms underlying its efficacy necessitate further investigation. Here, the study aims to elucidate the impact of ALA-PDT on the cancer cell viability, invasion and migration, alongside delineating the underlying molecular mechanisms., Methods: Cervical cancer SiHa cells were subjected to ALA and red light irradiation, and we then measured the ALA-PDT's effects on cell functions using various assays. The potential interaction between miR-152-3p and JAK1 was explored through bioinformatics analyses and validated by dual-luciferase reporter assays. Post-transfection with miR-152-3p and JAK1 vectors, cellular functions were re-evaluated. The efficacy of ALA-PDT in tumor suppression was further investigated through tumor transplantation experiment in vivo., Results: ALA-PDT markedly suppressed SiHa cell viability, invasion and migration, impacting critical markers of proliferation, apoptosis, and epithelial-mesenchymal transition(EMT). And these effects were echoed by the inhibition of miR-152-3p. JAK1 was identified as a direct target of miR-152-3p, and ALA-PDT was found to regulate the expression levels of miR-152-3p, consequently influencing the JAK1/STAT1 signaling pathway. Augmentation of miR-152-3p expression and inhibition of the JAK1/STAT1 pathway mitigated the anti-cancer effects of ALA-PDT, whereas JAK1 overexpression diminished these effects. In vivo analyses demonstrated that ALA-PDT suppressed tumor growth and modulated the miR-152-3p/JAK1/STAT1 pathway expression., Conclusions: ALA-PDT inhibits the viability, invasion, and migration of cervical cancer SiHa cells by modulating the miR-152-3p/JAK1/STAT1 axis, offering a promising therapeutic avenue for combating invasive cervical cancer., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest. No conflicting relationship exists for any author., (Copyright © 2024. Published by Elsevier B.V.)

Abstract Background Endometrial carcinoma (EC) is one common gynecological tumor, threatening physical and psychological health of females. Huge amount of essays indicated that long non-coding RNAs (lncRNAs) were widely reported to serve as a crucial regulator in the biological movements among multiple carcinomas, including EC. Methods RT-qPCR was implemented to detect the expression of target genes. Loss/gain-of-function experiments certified the impacts of OIP5-AS1 and miR-152-3p on EC cell progression. Results Data of this research suggested that powerful expression of OIP5-AS1 was discovered in EC cell lines. Loss/gain-of-function assays inferred that OIP5-AS1 promoted proliferative, migratory and invasive abilities, and Epithelial-Mesenchymal Transition (EMT). In addition, we identified miR-152-3p expression was negatively modulated by OIP5-AS1. OIP5-AS1 accelerated the development of EC cells via downregulating miR-152-3p expression. SLC7A5 was selected out as a downstream target of miR-152-3p. The competing relationship between OIP5-AS1 and SLC7A5 was corroborated by luciferase reporter assay. Eventually, the results of rescue assays indicated that SLC7A5 overexpression could restore the impacts of OIP5-AS1 ablation on the progression of EC cells. Conclusion Our research confirmed that OIP5-AS1 propeled the development of EC cells through targeting miR-152-3p/SLC7A5. OIP5-AS1 could be utilized as a target for EC treatment.

MicroRNAs (miRNAs) control the proliferation of thymic epithelial cells (TECs) for thymic involution. Previous studies have shown that expression levels of miR-152-3p were significantly increased in the thymus and TECs during the involution of the mouse thymus. However, the possible function and potential molecular mechanism of miR-152-3p remains unclear. This study identified that the overexpression of miR-152-3p can inhibit, while the inhibition of miR-152-3p can promote, the proliferation of murine medullary thymic epithelial cell line 1 (MTEC1) cells. Moreover, miR-152-3p expression was quantitatively analyzed to negatively regulate Smad2, and the Smad2 gene was found to be a direct target of miR-152-3p, using the luciferase reporter assay. Importantly, silencing Smad2 was found to block the G1 phase of cells and inhibit the cell cycle, which was consistent with the overexpression of miR-152-3p. Furthermore, co-transfection studies of siRNA–Smad2 (siSmad2) and the miR-152-3p mimic further established that miR-152-3p inhibited the proliferation of MTEC1 cells by targeting Smad2 and reducing the expression of Smad2. Taken together, this study proved miR-152-3p to be an important molecule that regulates the proliferation of TECs and therefore provides a new reference for delaying thymus involution and thymus regeneration. [ABSTRACT FROM AUTHOR]

Abstract Background Osteoarthritis (OA) is one kind of degenerative joint disease that happens in articular cartilage and other joint tissues. Long non-coding RNAs (lncRNAs) have been reported to serve as pivotal regulators in many diseases, including OA. However, the role and relevant regulatory mechanisms of CASC19 in OA remain unknown. Methods The expression levels of CASC19, miR-152-3p, and DDX6 were identified by reverse-transcription polymerase chain reaction (RT-qPCR). Cell viability and apoptosis were determined by Cell Counting Kit-8 (CCK-8) and flow cytometry assays, respectively. The relationship between miR-152-3p and CASC19 or DDX6 was predicted by bioinformatics tools and verified by the dual-luciferase reporter assay. Results CASC19 was verified to exhibit higher expression in OA tissues and cells. Moreover, inhibition of CASC19 weakened proinflammatory cytokine (IL-6, IL-8, and TNF-α) production and cell apoptosis but facilitated cell viability. Experiments of the ceRNA mechanism elucidated that miR-152-3p was a sponge for CASC19, and miR-152-3p targeted DDX6, suggesting that CASC19 sponged miR-152-3p to release DDX6. Finally, results from rescue assays proved that the impacts of CASC19 silencing on chondrocytes apoptosis and proinflammatory cytokine production could be reversed by DDX6 overexpression. Conclusions It was concluded that lncRNA CASC19 accelerated chondrocytes apoptosis and proinflammatory cytokine production to exacerbate osteoarthritis development through regulating the miR-152-3p/DDX6 axis. These findings may offer an effective biological target for OA treatment.

Abstract Background Long non-coding RNAs (lncRNAs) have been reported to exert crucial functions in regulating the progression of human cancers. However, the function and mechanism of long intergenic non-protein coding RNA 01089 (LINC01089) in non-small cell lung cancer (NSCLC) have not been revealed. Methods The expression level of LINC01089, microRNA (miRNA, miR)-152-3p and phosphatase and tensin homolog deleted onc hromosome ten (PTEN) mRNA was detected by quantitative real-time PCR (qRT-PCR). After gain-of-function and loss-of-function models were established with NSCLC cell lines, the proliferation, migration and invasion of NSCLC cells were detected by cell counting kit-8 (CCK-8) assay, scratch healing assay, Transwell assay, respectively. Dual luciferase reporter assay was employed to validate the binding relationship between miR-152-3p and LINC01089 or the 3’UTR of PTEN. Western blot was used to detect PTEN expression in NSCLC cells after LINC01089 and miR-152-3p were selectively modulated. Results LINC01089 was down-regulated in NSCLC tissues and cells. Functional experiments showed that knockdown of LINC01089 could promote the proliferation, migration and invasion of NSCLC cells, while over-expression of LINC01089 had the opposite effects. miR-152-3p was identified as a functional target for LIN01089, and miR-152-3p could reverse the function of LINC01089. Additionally, LINC01089 could up-regulate the expression level of PTEN via repressing miR-152-3p. Conclusions Down-regulation of LINC01089 promoted the progression of NSCLC through regulating miR-152-3p/PTEN axis.

Yu Yang,1 Pengfeng Gong,2 Dongwei Yao,3 Dong Xue,2 Xiaozhou He2 1Department of Hepatopancreatobiliary Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, People’s Republic of China; 2Department of Urology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, People’s Republic of China; 3Department of Urology, The Second People’s Hospital of Lianyungang, Lianyungang, Jiangsu, People’s Republic of ChinaCorrespondence: Xiaozhou HeDepartment of Urology, The Third Affiliated Hospital of Soochow University, No. 185, Juqian Road, Changzhou, 213000, People’s Republic of ChinaTel +86-519-68873211Email xiaozhouhe59@163.comBackground: Long noncoding RNAs (lncRNAs) have been regarded as crucial regulators in many cancers, including clear cell renal cell carcinoma (ccRCC). This research aimed to explore the biological role and molecular mechanism of lncRNA HCG18 in ccRCC.Materials and Methods: The expression levels of HCG18, miR-152-3p and RAB14 were examined by RT-qPCR. Cell viability, migration and invasion were examined by CCK-8 and transwell assays. Luciferase reporter and RIP assays were adopted to verify the interaction between miR-152-3p and HCG18 or RAB14.Results: It was found that HCG18 expression was highly expressed in ccRCC tissues and cells, and patients with high expression of HCG18 had a short overall survival time. Moreover, HCG18 depletion attenuated ccRCC cell viability, migration and invasion. In addition, miR-152-3p was confirmed as a downstream target of HCG18 and was inversely regulated by HCG18, and RAB14 was a target of miR-152-3p. Functional assays demonstrated that miR-152-3p silencing or RAB14 addition abolished the inhibitory effects of HCG18 knockdown on ccRCC progression.Conclusion: The results of the present study indicated that HCG18 accelerated the development and progression of ccRCC by upregulating RAB14 via sponging miR-152-3p, suggesting a potential therapeutic target for patients with ccRCC.Keywords: HCG18, miR-152-3p, RAB14, clear cell renal cell carcinoma

Yongfei Xu,1,2 Jianwen Zhang,1 Qiangqiang Zhang,3 Hangxing Xu,4 Linbo Liu1 1Department of Plastic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou City, Henan, People’s Republic of China; 2Department of Plastic Surgery, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang City, Henan, People’s Republic of China; 3Burn Plastic Surgery, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang City, Henan, People’s Republic of China; 4Department of Surgery, Luoyang Central Tunnel Hospital, Luoyang City, Henan, People’s Republic of ChinaCorrespondence: Linbo LiuDepartment of Plastic Surgery, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Jinshui District, Zhengzhou, 450000, Henan, People’s Republic of ChinaTel +86-13937196215Email pingtengfut8s@126.comBackground: Long non-coding RNA homeobox A11 antisense RNA (HOXA11-AS) was showed to participate in the progression of different kinds of tumors, but the specific role of HOXA11-AS in cutaneous melanoma is not entirely unambiguous.Methods: The levels of HOXA11-AS, microRNA-152-3p (miR-152-3p) and integrin alpha9 (ITGA9) were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was detected via 3-(4, 5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide (MTT), and apoptosis was measured by flow cytometry. The assessment of cell metastasis was performed by transwell migration and invasion assays. The protein levels were detected through Western blot. Dual-luciferase reporter assay was utilized to explore the target relationship among HOXA11-AS, miR-152-3p and ITGA9. The effect of HOXA11-AS on melanoma in vivo was investigated via xenograft experiment.Results: HOXA11-AS and ITGA9 were up-regulated while miR-152-3p was down-regulated in melanoma. Knockdown of HOXA11-AS refrained cell proliferation, metastasis and epithelial–mesenchymal transition (EMT) but induced apoptosis in melanoma cells. HOXA11-AS targeted miR-152-3p and overexpression of HOXA11-AS mitigated the miR-152-3p-induced effects on melanoma cellular behaviors. ITGA9 was a target of miR-152-3p and miR-152-3p inhibitor relieved the repression on proliferation, metastasis and EMT while elevation on apoptosis caused by si-ITGA9 via elevating ITGA9. HOXA11-AS knockdown restrained ITGA9 expression via up-regulating miR-152-3p. Suppression of HOXA11-AS inhibited melanoma progression in part through increasing miR-152-3p and decreasing ITGA9 expression in vivo.Conclusion: HOXA11-AS modulated proliferation, apoptosis, metastasis and EMT in melanoma cells by regulating miR-152-3p/ITGA9 axis in part. HOXA11-AS could promote melanoma development and be used as a promising biomarker in the diagnosis and treatment for cutaneous melanoma.Keywords: melanoma, HOXA11-AS, miR-152-3p, ITGA9

Background: miR-152-3p functions as a tumour suppressor in the progression of hepatic tumorigenesis. Herein, we further discussed the prognostic significance and immune infiltration of miR-152-3p and its potential gene target in hepatocellular carcinoma (HCC). Methods: The Cancer Genome Atlas (TCGA), Integrative Molecular Database of Hepatocellular Carcinoma (HCCDB), Human Protein Atlas (HPA) and Kaplan–Meier Plotter databases were used to evaluate miR-152-3p and roundabout guidance receptor 1 (ROBO1) expression, prognosis and immune infiltration. In vitro cell experiments, including cell proliferation and apoptosis, were evaluated using Cell Counting Kit 8 (CCK8) and terminal-deoxynucleotidyl transferase-mediated nick end labelling (TUNEL) assays. Results: Up-regulation of ROBO1 functioned as an oncogene associated with poor prognosis, immune cell enrichment and cell proliferation in HCC. ROBO1 was significantly positively correlated with the enrichment of multiple immune cells and their biomarkers. Enrichment of type-2 T-helper (Th2) cells is an unfavourable biomarker of HCC prognosis. GSEA revealed that ROBO1 correlated with apoptosis, mitosis and carcinogenic signalling pathways. Suppression of cell proliferation and the enhancement of cell apoptosis by miR-152-3p mimics were counteracted by overexpression of ROBO1 in HCC cells. Conclusion: ROBO1 expression is positively correlated with multiple immune checkpoint molecules, suggesting that ROBO1 may be a potential drug target to enhance the potency of immunotherapy. The miR-152-3p/ROBO1 signalling axis contributes to malignant progression and provides a prospective immunotherapeutic target for HCC. [ABSTRACT FROM AUTHOR]

In recent years, morbidity and mortality of prostate cancer (PCa) have increased dramatically, while mechanistic understanding of its onset and progression remains unmet. LncRNA SNHG3 has been proved to stimulate malignant progression of multiple cancers, whereas its functional mechanism in PCa needs to be deciphered. In this study, our analysis in the TCGA database revealed high SNHG3 expression in PCa tissue. Further analysis in starBase, TargetScan, and mirDIP databases identified the SNHG3/miR-152-3p/SLC7A11 regulatory axis. FISH was conducted to assess the distribution of SNHG3 in PCa tissue. Dual-luciferase reporter gene and RIP assays confirmed the relationship among the three objects. Next, qRT-PCR and western blot were conducted to measure expression levels of SNHG3, miR-152-3p, and SLC7A11. CCK-8, colony formation, Transwell, and flow cytometry were carried out to assess proliferation, migration, invasion, methionine dependence, apoptosis, and the cell cycle. It was noted that SNHG3 as a molecular sponge of miR-152-3p stimulated proliferation, migration, and invasion, restrained methionine dependence and apoptosis, and affected the cell cycle of PCa cells via targeting SLC7A11. Additionally, we constructed xenograft tumor models in nude mice and confirmed that knockdown of SNHG3 could restrain PCa tumor growth and elevate methionine dependence in vivo. In conclusion, our investigation improved understanding of the molecular mechanism of SNHG3 modulating PCa progression, thereby generating novel insights into clinical therapy for PCa. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the pathogenesis of colorectal cancer (CRC) and the effects of the long noncoding RNA plasmacytoma variant translocation 1 (PVT1) on CRC progression. Bioinformatics analysis verified PVT1 expression in tumor and normal tissues. Quantitative PCR and western blotting were used to measure mRNA and protein levels, respectively. The MTT, Transwell, colony formation, and in vivo assays were used to assess the effects of PVT1 on proliferation, migration, and invasion by CRC cells. Both PVT1 and microRNA (miR)‐152‐3p were shown to be colocalized in CRC cells using FISH assay. The target genes of miR‐152‐3p were predicted and verified by bioinformatics analysis, luciferase assay, and RNA pull‐down assay. The ChIP assay revealed that E2F3 binds with the promoter of MAPK8. We found that PVT1 was overexpressed in CRC specimens, and its expression was higher in CRC cells than normal intestinal cells. Overexpression of PVT1 enhanced the proliferation, migration, and invasion of CRC cells, whereas PVT1 knockdown inhibited these processes. MicroRNA‐152‐3p was a target of PVT1, and E2F3 was a target of miR‐152‐3p. Rescue experiments confirmed the interaction between miR‐152‐3p and PVT1 and between miR‐152‐3p and E2F3. Luciferase and ChIP assay results confirmed that E2F3 modulates the transcriptional activation of MAPK8. Long noncoding RNA PVT1 activated E2F3 signaling by sponging miR‐152‐3p. The PVT1/miR‐152‐3p/E2F3/MAPK8 axis promoted CRC progression. [ABSTRACT FROM AUTHOR]

Background: The dysregulation of LncRNAs is related to the malignant progression of many cancers. Objective: The study aimed to investigate the expression and the biological role of LncSNHG3 in hepatocellular carcinoma (HCC). Methods: The TCGA data of the LncSNHG3 in HCC were analyzed. The expression in HCC cell lines was detected by qRT-PCR. Proliferation, migration, and invasion of HepG2 and Huh7 were examined by cell counting kit-8, colony formation, transwell assays, and wound healing assays. At the same time, the interactions among LncSNHG3, miR-152-3p, and JAK1 were confirmed by dual-luciferase reporter assay, RNA immunoprecipitation, subcellular distribution. Xenograft tumor-bearing mice models were used to measure the effect of LncSNHG3 on the growth of HCC in vivo. The apoptosis and epithelial mesenchymal transition (EMT)-associated proteins were checked by WB and IHC. Results: LncSNHG3 was overexpressed in HCC tissues and cell lines. In addition, it is correlated with the tumor stage and survival time of HCC patients. Down-regulated LncSNHG3 could significantly suppress the EMT progression of HCC in vivo and in vitro. LncSNHG3 could promote the JAK1 expression by sponging miR-152-3p. Conclusions: LncSNHG3 acted as an oncogene and promoted the EMT procession in HCC by binding miR-152-3p and promoting JAK1 expression. Predictably, LncSNHG3 was used as a potential marker and will be used as a novel therapy target for HCC in the future. [ABSTRACT FROM AUTHOR]

Wang M, Wu Q, Fang M, Huang W, Zhu H. Onco Targets Ther. 2019;12:9513–9525. The Editor and Publisher of OncoTargets and Therapy wish to issue an Expression of Concern for the published article. Following publication, concerns were raised about the scientific integrity of the articles content. We reached out to the authors requesting they supply information that would confirm the integrity of the data. However, the authors did not provide the requested files and could not satisfy our requirements to confirm the authenticity of some types of data. Therefore, as we continue to work through the issues raised, we advise readers to interpret the information presented in the article with due caution. The authors have been notified about this Expression of Concern. Read the original article

Pei Ma,1 Lianhai Li,1 Fu Liu,1 Qi Zhao2 1Department of General Surgery, Nanyang First People’s Hospital, Nanyang City, Henan Province, People’s Republic of China; 2Department of Urological Surgery, Nanyang First People’s Hospital, Nanyang City, Henan Province, People’s Republic of ChinaCorrespondence: Qi ZhaoDepartment of Urological Surgery, Nanyang First People’s Hospital, No. 12, Renmin Road, Nanyang City, Henan Province 473010, People’s Republic of ChinaEmail qizhao880911@163.comBackground: The aberrant expression of long non-coding RNAs (lncRNAs) plays a pivotal role in the development and progression of multiple cancers, including gastric cancer (GC). However, the underlying molecular mechanisms of lncRNA HCG18 in GC remain unknown.Materials and Methods: The expression levels of HCG18, HNF1A, microRNA-152-3p (miR-152-3p), and DNAJB12 were determined by RT-qPCR. Cell viability, migration, and invasion were assessed by CCK-8, wound healing, and transwell assays, respectively. The interaction between miR-152-3p and HCG18 or DNAJB12 was predicted by bioinformatics analysis and verified by dual-luciferase reporter assay. The correlation between the gene expression levels was analyzed using Pearson’s correlation coefficient. Western blot was used to measure the levels of HNF1A, DNAJB12, epithelial-mesenchymal transition (EMT) proteins (E-cadherin and Vimentin), and proliferation-related protein (PCNA).Results: It was found that HCG18 was upregulated in GC tissues and cell lines, and knockdown of HCG18 inhibited the proliferation, migration, and invasion of GC cells. Patients with high HCG18 expression had a shorter overall survival time compared with those with low HCG18 expression. In addition, transcription factor HNF1A could bind to the HCG18 promoter to facilitate its transcription. The upregulation of HCG18 could abolish the inhibitory effect of miR-152-3p overexpression on GC cell progression. Furthermore, DNAJB12 was demonstrated to be a target gene of miR-152-3p in GC cells, and HCG18 enhanced DNAJB12 expression by competitively binding with miR-152-3p. Finally, rescue assays proved that overexpression of DNAJB12 partially restored HCG18 knockdown-attenuated progression of GC cells.Conclusion: Our results demonstrated that HNF1A-induced HCG18 overexpression promoted GC progression by competitively binding with miR-152-3p and upregulating DNAJB12 expression. These findings might provide potential treatment strategies for patients with GC.Keywords: HNF1A, HCG18, miR-152-3p, DNAJB12, gastric cancer

Meihua Wang,1,* Qi Wu,2,* Mingming Fang,3,* Wu Huang,4 Hong Zhu5 1Department of Pathology, Changzhou Tumor Hospital, Affiliated to Soochow University, Changzhou, People’s Republic of China; 2Department of Histology and Embryology, Heze Medical College, Heze, People’s Republic of China; 3Department of Radiotherapy, Changzhou Tumor Hospital, Affiliated to Soochow University, Changzhou, People’s Republic of China; 4Department of Neurosurgery, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou, People’s Republic of China; 5Department of Radiation Oncology, Minhang Branch of Cancer Hospital of Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wu HuangDepartment of Neurosurgery, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou, People’s Republic of ChinaEmail czeyhw@sina.comHong ZhuDepartment of Radiation Oncology, Minhang Branch of Cancer Hospital of Fudan University, Shanghai, People’s Republic of ChinaEmail honglei19830319@126.comBackground: Accumulating evidences suggest that microRNAs (miRNAs) play key roles in mediating glioblastoma progression. Decreased expression of miR-152-3p was reported in several cancer types including glioblastoma.Methods: The sensitivity of glioblastoma cells to cisplatin was assessed by the cell counting kit-8 assay and flow cytometry analysis. The expression of miR-152-3p was determined by RT-qPCR method. Bioinformatic analysis, dual luciferase reporter assay and Western blot were used to explore the target gene of miR-152-3p. The association between miR-152-3p and SOS1 was confirmed in glioblastoma tissues by Pearson correlation analysis.Results: In the current study, we discovered that overexpression of miR-152-3p increased cisplatin sensitivity while inhibition of miR-152-3p decreased cisplatin sensitivity in glioblastoma cells (T98G and U87). In addition, miR-152-3p augmented cell apoptosis induced by cisplatin treatment. It was further predicted and validated that SOS1, a protein involved in regulating chemotherapy sensitivity, was a direct target gene of miR-152-3p. SOS1 was proven to suppress the cytotoxic effect of cisplatin in glioblastoma. Transfection of recombinant SOS1 could effectively reverse the increased cisplatin sensitivity induced by miR-152-3p overexpression in T98G. Furthermore, overexpression of SOS1 reduced the percentage of apoptotic cells increased by miR-152-3p mimic in the presence of cisplatin in T98G. More importantly, a significant negative correlation between miR-152-3p levels and SOS1 levels was observed in glioblastoma tissues collected from 40 patients.Conclusion: Our study identified miR-152-3p as a chemotherapy sensitizer in glioblastoma.Keywords: glioblastoma, miR-152-3p, SOS1, cisplatin

Background: Inevitable resistance to chemotherapeutic drugs has become a major obstacle for the clinical treatment of multiple myeloma (MM). Circular RNAs (circRNAs) can regulate the chemoresistance in different tumors. Our study was to explore the regulation of circRNA arginine-glutamic acid dipeptide repeats (circRERE) in bortezomib (BTZ) resistance of MM. Methods: CircRERE, microRNA-152-3p (miR-152-3p) and cluster of differentiation 47 (CD47) levels were assayed through the quantitative real-time polymerase chain reaction (qRT-PCR). Cell sensitivity to BTZ was analyzed using Cell Counting Kit-8 (CCK-8) assay. Cell proliferation and apoptosis were determined via colony formation assay and flow cytometry, respectively. The detection of all proteins was conducted by western blot. The target binding was analyzed via the dual-luciferase reporter assay and RIP assay. Results: We found the upregulation of circRERE in BTZ-resistant MM samples and cells. BTZ resistance was inhibited after circRERE expression was downregulated in MM cells. CircRERE was identified to act as a miR-152-3p sponge. The effect of circRERE on the BTZ resistance was associated with the sponge function for miR-152-3p. CD47 was a target for miR-152-3p and circRERE could sponge miR-152-3p to generate the expression regulation of CD47. MiR-152-3p facilitated the susceptibility of MM cells to BTZ by targeting CD47. Conclusion: These results suggested that circRERE could suppress the BTZ resistance in MM cells by mediating the miR-152-3p/CD47 axis.

Background: Increasing evidence has suggested that circular RNAs (circRNAs) may act as an important regulatory factor in tumor progression. However, how circRNAs exert their functions in triple‐negative breast cancer (TNBC) remains not clearly understood. Methods: First, circRNA microarrays were conducted to identify aberrantly expressed circRNAs in TNBC tissues. Kaplan–Meier survival analysis was conducted to calculate the correlation between the level of hsa_circRNA_102229 and outcomes of patients with TNBC. The effect of hsa_circRNA_102229 and serine/threonine‐protein kinase PFTAIRE 1 (PFTK1) on TNBC cells was clarified by cell counting kit‐8, transwell and wound healing assays, as well as by a flow cytometry. The molecular mechanism of hsa_circRNA_102229 was clarified through bioinformatics, a dual‐luciferase reporter assay, western blotting, fluorescence in situ hybridization and real‐time polymerase chain reaction. Tumor xenograft experiments were performed to analyze growth and metastasis of TNBC in vivo. Results: In TNBC tissues and cells, hsa_circ_102229 was remarkably up‐regulated. Patients with TNBC presenting high hsa_circ_102229 exhibited poor prognosis. Moreover, hsa_circ_102229 could promote the migration, proliferation and invasion, whereas it inhibited the apoptosis of TNBC cells. Furthermore, hsa_circ_102229 directly targeted miR‐152‐3p and could regulate the expression of PFTK1 by targeting miR‐152‐3p. Rescue assays suggested that hsa_circ_102229 may exert its function in TNBC cells by regulating PFTK1. Additionally, knockdown of hsa_circ_102229 slowed down TNBC tumorigenesis and lung metastasis in a tumor xenograft animal model. Conclusions: Hsa_circ_102229 might serve as a competing endogenous RNA (ceRNA) to modulate PFTK1 expression via regulating miR‐152‐3p to affect the functions of TNBC cells. Hsa_circ_102229 acts as a newly discovered biomarker for TNBC treatment. [ABSTRACT FROM AUTHOR]

Background: Endometrial carcinoma (EC) is one common gynecological tumor, threatening physical and psychological health of females. Huge amount of essays indicated that long non-coding RNAs (lncRNAs) were widely reported to serve as a crucial regulator in the biological movements among multiple carcinomas, including EC. Methods: RT-qPCR was implemented to detect the expression of target genes. Loss/gain-of-function experiments certified the impacts of OIP5-AS1 and miR-152-3p on EC cell progression. Results: Data of this research suggested that powerful expression of OIP5-AS1 was discovered in EC cell lines. Loss/gain-of-function assays inferred that OIP5-AS1 promoted proliferative, migratory and invasive abilities, and Epithelial-Mesenchymal Transition (EMT). In addition, we identified miR-152-3p expression was negatively modulated by OIP5-AS1. OIP5-AS1 accelerated the development of EC cells via downregulating miR-152-3p expression. SLC7A5 was selected out as a downstream target of miR-152-3p. The competing relationship between OIP5-AS1 and SLC7A5 was corroborated by luciferase reporter assay. Eventually, the results of rescue assays indicated that SLC7A5 overexpression could restore the impacts of OIP5-AS1 ablation on the progression of EC cells. Conclusion: Our research confirmed that OIP5-AS1 propeled the development of EC cells through targeting miR-152-3p/SLC7A5. OIP5-AS1 could be utilized as a target for EC treatment. [ABSTRACT FROM AUTHOR]

This study aimed to explore the role of small nucleolar RNA host gene 14 (SNHG14) in the pathogenesis of diffuse large-B-cell lymphoma (DLBCL). DLBCL cell lines (OCI-Ly7 and OCI-Ly3) and specimens from patients were collected to evaluate the roles of SNHG14 in DLBCL pathogenesis. The results showed that SNHG14 expression increased and miR-152-3p expression decreased in DLBCL tissues and cell lines, indicating a negative correlation between miR-152-3p and SNHG14 expression. Moreover, SNHG14 was found to promote DLBCL growth, migration, and EMT-like processes in vitro, and directly inhibits miR-152-3p gene expression via sequestration of the miR-152-3p transcripts in DLBCL. Additionally, SNHG14/miR-152-3p inhibits apoptosis and promotes cell proliferation on cytotoxic T lymphocytes (CTLs) in DLBCL via the PD-1/PD-L1 checkpoint. Furthermore, both the immune escape and progression of DLBCL are advanced by SNHG14 expression via its interactions with miR-152-3p. Collective, this suggests that SNHG14 is a potential diagnostic, prognostic, and therapeutic target for DLBCL. [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis (OA) is one kind of degenerative joint disease that happens in articular cartilage and other joint tissues. Long non-coding RNAs (lncRNAs) have been reported to serve as pivotal regulators in many diseases, including OA. However, the role and relevant regulatory mechanisms of CASC19 in OA remain unknown. Methods: The expression levels of CASC19, miR-152-3p, and DDX6 were identified by reverse-transcription polymerase chain reaction (RT-qPCR). Cell viability and apoptosis were determined by Cell Counting Kit-8 (CCK-8) and flow cytometry assays, respectively. The relationship between miR-152-3p and CASC19 or DDX6 was predicted by bioinformatics tools and verified by the dual-luciferase reporter assay. Results: CASC19 was verified to exhibit higher expression in OA tissues and cells. Moreover, inhibition of CASC19 weakened proinflammatory cytokine (IL-6, IL-8, and TNF-α) production and cell apoptosis but facilitated cell viability. Experiments of the ceRNA mechanism elucidated that miR-152-3p was a sponge for CASC19, and miR-152-3p targeted DDX6, suggesting that CASC19 sponged miR-152-3p to release DDX6. Finally, results from rescue assays proved that the impacts of CASC19 silencing on chondrocytes apoptosis and proinflammatory cytokine production could be reversed by DDX6 overexpression. Conclusions: It was concluded that lncRNA CASC19 accelerated chondrocytes apoptosis and proinflammatory cytokine production to exacerbate osteoarthritis development through regulating the miR-152-3p/DDX6 axis. These findings may offer an effective biological target for OA treatment. [ABSTRACT FROM AUTHOR]

Cisplatin (DDP) resistance is a key problem for effective treatment of gastric cancer (GC). Circular RNA PVT1 (circPVT1) acts as a vital regulator in the progression and development of various cancers. However, the in-depth mechanism of circPVT1 in GC resistance to DDP is still unclear. Quantitative real-time polymerase chain reaction was executed for the detection of the expression of circPVT1, miR-152-3p, and hepatoma-derived growth factor (HDGF) mRNA in GC tissues and cells. Western blot was used to detect the levels of HDGF protein, Bax, cleaved-casp-3, Bcl-2, p-PI3K, and p-AKT in tissue samples and/or cells. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry assays were performed to determine the viability, proliferation, and apoptosis of DDP-resistant GC cells. The relationship between miR-152-3p and circPVT1 or HDGF was confirmed by dual-luciferase reporter assay. The biological role of circPVT1 in vivo was confirmed with a xenograft tumor model. CircPVT1 and HDGF mRNA were upregulated while miR-152-3p was downregulated in chemoresistance tissues and DDP-resistant GC cells. Both circPVT1 and HDGF inhibition elevated cell sensitivity to DDP, suppressed cell viability, proliferation, and induced cell apoptosis in DDP-resistant GC cells. The MiR-152-3p inhibitor reversed the influence of circPVT1 silencing on DDP sensitivity, viability, proliferation, and apoptosis of DDP-resistant GC cells. Moreover, circPVT1 regulated the HDGF/PI3K/AKT pathway through sponging miR-152-3p. In addition, circPVT1 knockdown reduced the malignancy of DDP-resistant GC cells in vivo. CircPVT1 regulated the chemoresistance and malignancy of GC through modulating HDGF expression via sponging miR-152-3p, providing a theoretical basis for the development of effective therapeutic strategies for GC. [ABSTRACT FROM AUTHOR]

Kinesin family member 14 (KIF14) overexpression has been linked to tumor progression and metastasis in different malignancies, but its precise molecular mechanism in bladder cancer (BLCA) remains unclear. The expression of KIF14 in BLCA and its relationship with clinical outcomes were assessed. Functional investigations on KIF14 were conducted using CCK-8, Transwell experiment, colony formation, scratch motility assays, and flow cytometry. We examined the downstream route of KIF14 and identified its upstream regulatory factor through luciferase reporter experiments and bioinformatics tools. Our findings demonstrated that increased KIF14 expression was associated with poor survival prognosis in BLCA patients. Deletion of KIF14 affected cell cycle progression, induced apoptosis, and inhibited cell growth, migration, and invasion. GSEA analysis revealed a strong association between KIF14 expression and the PI3K/AKT signaling pathway. Further research showed that KIF14 deletion decreased the levels of p-PI3K, p -AKT, FOXM1, and CCNB1. We also found that has-miR-152-3p (miR-152) suppressed BLCA cell growth by post-transcriptionally regulating KIF14 expression. Our findings suggest that targeting KIF14 could alter the PI3K/AKT and FOXM1-CCNB1 axis, leading to growth inhibition, cell cycle arrest, and induction of apoptosis in BLCA cells. Additionally, miR-152 directly regulates KIF14 expression at the post-transcriptional level. Overall, KIF14 represents a promising therapeutic target for BLCA clinical therapy. • MicroRNA-152 specifically targets Kinesin Family Member 14. • Kinesin Family Member 14 promotes the advancement of Bladder Cancer via PI3K/AKT Pathway. • KIF14 represents a promising therapeutic target for BLCA clinical therapy. [ABSTRACT FROM AUTHOR]

Abstract Background Long non-coding RNA plays a crucial role in the occurrence and progression of glioma. We aimed to explore the function of LINC00174 in cell proliferation, apoptosis, migration, invasion and glycolysis of glioma cells, and investigate the molecular mechanism involved. Methods LINC00174 expression in glioma tissues and peritumoral brain edema (PTBE) tissues was examined by RT-qPCR and in situ hybridization. The CCK-8, TUNEL, wound healing, transwell, and ELISA assays were performed to identify the effects of LINC00174 knockdown on cell viability, apoptosis, migration, invasion, and glycolysis, respectively. RNA immunoprecipitation, dual-luciferase reporter, RNA pull down, and western blot assays were performed to explore the molecular mechanisms of LINC00174 in glioma cells. A nude mouse xenograft model was used to investigate the role of LINC00174 in xenograft glioma growth. Results LINC00174 was overexpressed in glioma tissues and cell lines. LINC00174 knockdown inhibited cell proliferation, migration, invasion and glycolysis of glioma cells, and LINC00174 exerted a tumorigenesis role. LINC00174 could interact with miR-152-3p/SLC2A1 axes. The miR-152-3p inhibitor or the SLC2A1 overexpression could rescue the anti-tumor effect of LINC00174 knockdown on glioma cells. Moreover, downregulation of LINC00174 also inhibited tumor volume and delayed the tumor growth in vivo. Conclusion LINC00174 accelerated carcinogenesis of glioma via sponging miR-1523-3p and increasing the SLC2A1 expression, which could be considered as a molecular target for glioma diagnosis and therapy.

AIM:To investigate the effect of microRNA-152-3p(miR-152-3p)targeting insulin-like growth factor 1(IGF1)gene on high glucose-induced retinal pigment epithelial ARPE-19 cell activity and apoptosis, and to explore its role mechanism. METHODS: High glucose was induced into ARPE-19 cells and transfected with miR-152-3p mimics. MTT assay was used to detect cell proliferation activity. Flow cytometry was used to detect apoptosis. Fluorescence quantitative PCR(RT-PCR)was used to detect cells. The expression levels of IGF1 and VEGF in the cells were detected by Western blot and the binding relationship between IGF1 and miR-152-3p was detected by the dual luciferase reporter gene.RESULTS:High glucose can decrease the activity of ARPE-19 cells, increase the apoptosis rate, inhibit the expression of miR-152-3p and increase the expression of IGF1 and VEGF. Over expression of miR-152-3p can up-regulate high glucose-induced cells. Increased activity and increased apoptosis inhibited the expression of IGF1 and VEGF. The dual luciferase reporter gene assay verified that IGF1 is the target gene of miR-152-3p.CONCLUSION: miR-152-3p can inhibit the inhibition of high glucose-induced ARPE-19 cell activity and increase apoptosis by targeting IGF1 gene.

Background: Long non-coding RNAs (lncRNAs) have been reported to exert crucial functions in regulating the progression of human cancers. However, the function and mechanism of long intergenic non-protein coding RNA 01089 (LINC01089) in non-small cell lung cancer (NSCLC) have not been revealed. Methods: The expression level of LINC01089, microRNA (miRNA, miR)-152-3p and phosphatase and tensin homolog deleted onc hromosome ten (PTEN) mRNA was detected by quantitative real-time PCR (qRT-PCR). After gain-of-function and loss-of-function models were established with NSCLC cell lines, the proliferation, migration and invasion of NSCLC cells were detected by cell counting kit-8 (CCK-8) assay, scratch healing assay, Transwell assay, respectively. Dual luciferase reporter assay was employed to validate the binding relationship between miR-152-3p and LINC01089 or the 3'UTR of PTEN. Western blot was used to detect PTEN expression in NSCLC cells after LINC01089 and miR-152-3p were selectively modulated. Results: LINC01089 was down-regulated in NSCLC tissues and cells. Functional experiments showed that knockdown of LINC01089 could promote the proliferation, migration and invasion of NSCLC cells, while over-expression of LINC01089 had the opposite effects. miR-152-3p was identified as a functional target for LIN01089, and miR-152-3p could reverse the function of LINC01089. Additionally, LINC01089 could up-regulate the expression level of PTEN via repressing miR-152-3p. Conclusions: Down-regulation of LINC01089 promoted the progression of NSCLC through regulating miR-152-3p/PTEN axis. [ABSTRACT FROM AUTHOR]

Introduction: There is growing evidence that long non-coding RNAs (lncRNAs) are correlated with malignancy in the modulation of tumor progression. This study aims to investigate the effect of homeobox protein (HOX) transcript antisense RNA (HOTAIR) on the migration and invasion of ESC.Material and Methods: Starbase was used to identify miRNAs with complementary base pairing with HOTAIR. RNA pull-down and qRT-PCR were employed to investigate the effect of HOTAIR on miR-152-3p. In vitro cell migration and invasion assays were performed to assess the effects of HOTAIR and miR-152-3p on ESC. Computational software, TargetScan, was then used to identify the potential target of miR-152-3p, and their relationship was verified by immunoblotting analysis, qRT-PCR and luciferase reporter assay.Results: Starbase predicted a potential miR-152-3p binding site in HOTAIR, which was validated by RNA pull-down assay. HOTAIR was negatively correlated with miR-152-3p in ESC. Moreover, HOTAIR promoted migration and invasion of ESC. The oncogenic activity of HOTAIR was partly through its negative regulation of miR-152-3p. LIN28B was identified to be a direct target of miR-152-3p. A negative correlation between LIN28B and miR-152-3p was observed in ESC. In addition, overexpression of miR-152-3p suppressed the progression of ESC by directly targeting and regulating LIN28B.Conclusions: Our results reveal that HOTAIR may be a driver of ESC through inhibiting miR-152-3p, a tumor suppressor, suggesting that miR-152-3p may be a potential target for advanced ESC therapeutic treatment. [ABSTRACT FROM AUTHOR]

To investigate the difference in protein expression between hepatocellular carcinoma ( HCC) patients with recurrence and those with good prognosis, the differential expression and regulatory mechanism of miR - 152 - 3 p target proteins, and the role of miR - 152 - 3p in the recurrence of HCC. Methods TMT - labeled proteomic sequencing and RT - PCR were used to measure the expression of proteins and the expression of miR - 152 - 3 p in the HCC tissue of six patients with recurrence at 2 years after HCC resection and six patients with good prognosis at 5 years. Six databases were used to analyze the target genes of miR - 152 - 3p, and Gene Ontology, DAVID, and REACTOME databas es were used to perform target gene screening, enrichment annotation, and signal transduction pathway enrichment analysis. Gene mutation frequency and survival curve analysis were performed for the target genes of miR - 152 - 3p to verify the role of miR - 152 - 3 p target genes in patients with HCC recurrence. The independent samples t - test was used for comparison of continuous data between two groups, and a Kaplan - Meier analysis was performed to investigate the survival rates of liver - related genes. Results Compared with the patients with HCC recurrence, the patients with good prognosis after HCC resection had a significantly higher transcriptional expression level of miR - 152 - 3 p in HCC tissue ( P < 0. 05). The results of protein sequencing showed that there were 365 differentially expressed proteins in HCC tissue between the patients with good prognosis and the patients with recurrence, and the analysis of HCC recurrence databases showed that 17 proteins were regulated by miR - 152 - 3 p. Further analysis of the signaling pathways showed that the function of the 17 target genes regulated by miR -152 - 3p was enriched in the translation and regulation of mitochondria and ribosome, and multiple enrichment revealed that six target genes were closely associated with mitochondrial respiratory chain complex, i. e ., AKAPl, FOXREDl, MRPL28, MRPL50, SHCl, and STAUl. Gene mutation frequency and survival curve analysis showed that the loss or weakening of the function of mitochondrial respiratory chain - related target proteins seriously affected the prognosis and survival rate of patients. Conclusion There is a significant difference in the expression of miR - 152 - 3p in HCC tissue between patients with good prognosis and those with recurrence after HCC resection, and miR - 152 - 3 p may lead to the recurrence of HCC by regulating the target genes AKAPl, FOXREDl, MRP128, MRPL50, SH Cl, and STA Ul, acting on the mitochondrial respiratory chain, and affecting the oxidative respiratory function of cells. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) control the proliferation of thymic epithelial cells (TECs) for thymic involution. Previous studies have shown that expression levels of miR-152-3p were significantly increased in the thymus and TECs during the involution of the mouse thymus. However, the possible function and potential molecular mechanism of miR-152-3p remains unclear. This study identified that the overexpression of miR-152-3p can inhibit, while the inhibition of miR-152-3p can promote, the proliferation of murine medullary thymic epithelial cell line 1 (MTEC1) cells. Moreover, miR-152-3p expression was quantitatively analyzed to negatively regulate Smad2, and the Smad2 gene was found to be a direct target of miR-152-3p, using the luciferase reporter assay. Importantly, silencing Smad2 was found to block the G1 phase of cells and inhibit the cell cycle, which was consistent with the overexpression of miR-152-3p. Furthermore, co-transfection studies of siRNA–Smad2 (siSmad2) and the miR-152-3p mimic further established that miR-152-3p inhibited the proliferation of MTEC1 cells by targeting Smad2 and reducing the expression of Smad2. Taken together, this study proved miR-152-3p to be an important molecule that regulates the proliferation of TECs and therefore provides a new reference for delaying thymus involution and thymus regeneration.

Long-noncoding RNA taurine upregulated gene 1 (TUG1) participates in nervous system diseases, but its function in Parkinson's disease (PD) remains unclear. This study explored the function and mechanism of TUG1 in PD. A PD model was constructed using SH-SY5Y cells induced by 1-methyl-4-phenylpyridinium (MPP+) in vitro and mice treated by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in vivo. The expressions of TUG1, miR-152-3p, phosphatase and tensin homologue (PTEN), tyrosine hydroxylase (TH), and Bcl-2, and cleaved caspase-3 expressions were determined by quantitative reverse transcription-PCR and Western blotting. The viability, apoptosis, reactive oxygen species, and release of inflammatory factors from SH-SY5Y cells and substantia nigra tissues were detected by commercial kits. The interaction between TUG1 and miR-152-3p was analyzed by dual-luciferase reporter assay. Hematoxylin/eosin and immunohistochemical staining was performed for assessing the pathological damage and proportion of TH-positive cells. In PD cell model and mice model, TUG1 expression was upregulated and that of miR-152-3p was downregulated. Further research showed that TUG1 sponged and regulated miR-152-3p expression. Silencing of TUG1 not only protected SH-SY5Y cells against cell apoptosis, oxidative stress, and neuroinflammation in vitro, pathological damage and neuroinflammation in vivo, but also suppressed the expressions of PTEN and cleaved caspase-3, and increased the expressions of TH and Bcl-2 in MPP+-treated SH-SY5Y cells. However, the protective role of siTUG1 in SH-SY5Y cells was significantly inhibited by the miR-152-3p inhibitor. Thus, knocking down TUG1 might have a protective effect on PD through the miR-152-3p/PTEN pathway. [ABSTRACT FROM AUTHOR]

Background The occurrence of pathological cardiac fibrosis is attributed to tissue hypoxia. Circular RNAs play significant regulatory roles in multiple cardiovascular diseases and are involved in the regulation of physiological and pathophysiological processes. CircHIPK3 has been identified as the one of the most crucial regulators in cardiac fibrosis. However, the mechanisms by which circHIPK3 regulates cardiac fibrosis under hypoxia remain unclear. Our study aimed to determine circHIPK3 expression in cardiac fibroblasts (CFs) and investigate the functions of circHIPK3 in hypoxia environment. Methods The expression level of circHIPK3 in CFs under hypoxia (1% O2) was analyzed by qRT-PCR. The role of circHIPK3 on the proliferation and migration of CFs were determined by EdU, cell wound scratch assay and cell cycle. The expression of proteins associated with phenotypic transformation in CFs in vitro was examined by immunofluorescence assay and western blot. Bioinformatics analysis, dual luciferase activity assay and RNA fluorescent in situ hybridization assay revealed that miR-152-3p was identified as a target of circHIPK3 and that TGF-β2 was targeted by miR-152-3p. Results CircHIPK3 expression was significantly upregulated in CFs in a hypoxic environment. In vitro, overexpressing circHIPK3 obviously promoted CF proliferation, migration and phenotypic changes under hypoxia, but those processes were suppressed by circHIPK3 silencing. CircHIPK3 acted as an endogenous miR-152-3p sponge and miR-152-3p aggravated circHIPK3 silencing induced inhibition of CF proliferation, migration, phenotypic transformation and TGF-β2 expression in vitro. In summary, circHIPK3 plays a pivotal role in the development of cardiac fibrosis by targeting the miR-152-3p/TGF-β2 axis. Conclusions These findings demonstrated that circHIPK3 acted as a miR-152-3p sponge to regulate CF proliferation, migration and phenotypic transformation through TGF-β2, revealing that modulation of circHIPK3 expression may represent a potential target to promote the transition of hypoxia-induced CFs to myofibroblasts.

Abstract Background Prostate cancer (PCa) is a major cause of morbidity and mortality in men worldwide. MicroRNAs are globally downregulated in PCa, especially in poorly differentiated tumors. Nonetheless, the underlying mechanisms are still elusive. Herein, using combined analysis of microRNAs expression and genomewide DNA methylation, we aimed to identify epigenetically downregulated microRNAs in PCa. Results We found that miR-152-3p was underexpressed in PCa and that lower expression levels were associated with promoter hypermethylation in accordance with TCGA dataset analysis. Functional in vitro assays suggest that miR-152-3p suppresses cell viability and invasion potential, whereas it promotes cell cycle arrest at S and G2/M phases. Additionally, miR-152-3p expression was associated with longer disease-free survival in PCa patients from TCGA. Finally, TMEM97, which is overexpressed in PCa, was identified as a novel miR-152-3p target gene. Conclusions Our findings demonstrate the advantages of using a combinatory approach to identify microRNAs downregulated due to aberrant promoter methylation. MiR-152-3p downregulation and promoter methylation was found to be prevalent in primary PCa, which impairs its role in control of cell viability, cell cycle regulation and invasion.

Acute kidney injury (AKI) is one of the most common and serious complications in the development of sepsis. Many microRNAs are closely related to the occurrence, development, and prognosis of sepsis AKI (but the effect and mechanism of miR‐152‐3p in it is unclear). Meanwhile, the ERBB receptor feedback inhibitor 1 (ERRFI1) has a negative regulatory effect on signal transducer and activator of transcription 3 (STAT3) phosphorylation on uterine epithelial cells. But, the relationship between miR‐152‐3p and renal function, inflammatory factors, prognosis in AKI, and the mechanism is not clear. Analyzing sepsis‐induced AKI rats and the cell model, our results revealed that miR‐152‐3p was upregulated in septic AKI patients and positively correlated with serum creatinine, urea nitrogen, interleukin 1β (IL‐1β) and tumor necrosis factor α (TNF‐α). Downregulation of miR‐152‐3p with the inhibitor could dramatically attenuate caspase‐3, bromodeoxyuridine and IL‐1β, and TNF‐α in the AKI rats' model. Furthermore, downregulation of miR‐152‐3p attenuated lipopolysaccharide‐induced apoptosis and inflammatory response in HK‐2 and HEK293 cells. To further explore the mechanisms, we found ERRFI1 was appreciably downregulated and STAT3 was upregulated in AKI, whereas ERRFI1 was radically upregulated and STAT3 was greatly downregulated after the addition of miR‐152‐3p inhibitor, no matter in vivo or in vitro. Summarily, our study confirmed that miR‐152‐3p could promote the expression of STAT3 by targeting ERRFI1, aggravate cell apoptosis and inflammatory response, and thereby aggravate kidney injury in sepsis AKI. [ABSTRACT FROM AUTHOR]

Background: The current study aims to investigate the expression and potential role of exosome-derived miR-152- 3p in acute ischemic stroke (AIS) patients. Methods: Exosomes were isolated from AIS patients and healthy controls. The level of exosome miR-152-3p was examined using RT-PCR. Receiver operating characteristic (ROC) curves were used to assess exosome miR-152- 3p as a biomarker, and the area under the curve (AUC) was reported. Results: Our data showed that the expression of serum exosome miR-152-3p in patients with AIS was significantly lower than in healthy controls. In contrast to those with NIHSS score < 7, the level of exosome miR-152-3p was significantly reduced in AIS patients with NIHSS score ≥ 7, indicating that the decrease of exosome miR-152-3p level is significantly related to the severity of endothelial injury. Moreover, the lowest level of exosome miR-152-3p was found in large-artery atherosclerosis (LAA) patients compared to that in small-vessel occlusion (SAA), cardioembolism (CE) and stroke of undetermined etiology (SUE) group. In addition, exosome miR-152-3p level was significantly lower in acute phase than in chronic phase. ROC curve showed that the AUC of exosome miR-152-3p level was 0.935, which indicated that exosome miR-152-3p level could distinguish AIS patients from non-healthy controls. Conclusions: In summary, exosome miR-152-3p is a risk factor of cerebral infarction. Enhancing the expression of exosome miR-152-3p in the circulating system may be a promising strategy for the prevention and treatment of AIS. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) accounts for over twenty percent of hematological cancer-related death worldwide. Long non-coding RNA (lncRNA) H19 is associated with multiple tumorigenesis and is increased in MM, but the underlying mechanism of H19 in MM is unclear. In this study, the expression of H19, miR-152-3p and BRD4 in MM patients was evaluated by qRT-PCR and Western blotting. Colony formation and flow cytometry analysis were used to determine the effects of H19 and miR-152-3p on MM cell proliferation, apoptosis and cell cycle. Luciferase reporter assay was conducted to confirm the interaction among H19, miR-152-3p and BRD4. Nude mice xenograft model was established, and the cell proliferation and apoptosis were evaluated by immunohistochemistry (IHC) staining and TUNEL assay. We found that levels of H19 and BRD4 were up-regulated, and the expression of miR-152-3p was down-regulated in MM patients. Dual luciferase reporter assay showed H19 targeted miR-152-3p to promote BRD4 expression. Knockdown of H19 repressed proliferation, and enhanced apoptosis and cell cycle G1 arrest by up-regulating miR-152-3p in MM cells. Furthermore, H19 knockdown suppressed the growth of xenograft tumor, and reduced Ki-67 and BRD4 level, as well as increased cell apoptosis in xenograft tumor tissues. Taken together, H19 knockdown suppresses MM tumorigenesis via inhibiting BRD4-mediated cell proliferation through targeting miR-152-3p, implying that H19 may be a promising biomarker and drug target for MM. [ABSTRACT FROM AUTHOR]

Abstract Background MiRNAs are involved in aberrant DNA methylation through regulation of DNA methyltransferases (DNMTs) in the pathogenesis and progression of glioblastomas (GBM). MiR-152-3p was down-expressed in human malignancies, and served as a tumor suppressor. Neurofibromatosis type 2 (NF2) was significantly decreased in GBM tissues with a high level of methylation. However, the link between miR-152-3p, DNMT1 and methylation of NF2 in GBM is not clearly established. This study was conducted to detect the mechanism between miR-152-3p, DNMT1 and NF2 in GBM. Methods The levels of DNMT1 and NF2 expression were studied by qRT-PCR, Western blot, immunofluorescence, and immumohistochemical staining. Methylation in the promoter region of NF2 was detected by methylation-specific PCR and bisulfate genomic sequencing PCR. Cell proliferation was examined by Cell-Counting Kit-8 and 5-ethynyl-2′-deoxyuridine assay, and cell invasion was evaluated by transwell assay. Flow cytomery and Hoechst staining were used to analyze cell apoptosis. A dual luciferase system was used to confirm the relationship between miR-152-3p and DNMT1. Results Methylation of NF2 and DNMT1 was markedly increased, and miR-152-3p was downregulated in GBM tissues and glioma cells. Both knockdown of DNMT1 and overexpression miR-152-3p showed that demethylation activated the expression of NF2. Furthermore, miR-152-3p directly targeted DNMT1. Both miR-152-3p overexpression and DNMT1 knockdown significantly induced cell apoptosis and inhibited invasive activity. This was also observed after NF2 overexpression. Conclusions These results indicated that miR-152-3p can inhibit glioma cell proliferation and invasion activities by decreasing DNMT1. The restoration of miR-152-3p may have therapeutic application in the treatment of GBM.