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Circular RNA HIPK3 induces cell proliferation and inhibits apoptosis in non-small cell lung cancer through sponging miR-149.

ABSTRACT: Circular RNAs (circRNAs) are a class of endogenous noncoding RNAs that are demonstrated to be potent regulators in the development of various types of human cancers, including non-small cell lung cancer (NSCLC). In the present study, the level of circRNA-HIPK3 were measured by Taq-man based quantitative real-time PCR (qRT-PCR) analysis in both NSCLC patient specimens and cells, which showed that circRNA-HIPK3 was upregulated in both NSCLC tissues and cell lines. Cell counting kit-8 (CCK-8), migration and flow-cytometry assays indicated that circRNA-HIPK3 participated in the regulation of the proliferation, migration, invasion and apoptosis of NSCLC cells. MiR-193a expression was increased by circHIPK3 silencing. We then showed that miR-149 interacts with FOXM1 by binding to the 3'-untranslated region (UTR). Further, ectopic overexpression of miR-149 by transfecting miR-149 mimics significantly inhibited growth, migration and invasion of HSCLCs, which was found to be mediated through FOXM1. Moreover, miR-149 overexpression decreases the viability and proliferation of HSCLCs. Therefore, our data suggest that circHIPK3 regulates the function of NSCLCs through miR-149-mediated FOXM1 expression regulation, potentially providing a novel insight into the pathogenesis of NSCLC.

SUBMITTER: Lu H

PROVIDER: S-EPMC7012091 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Circular RNA HIPK3 induces cell proliferation and inhibits apoptosis in non-small cell lung cancer through sponging miR-149.

Lu Huibin H Han Xinwei X Ren Jianzhuang J Ren Kewei K Li Zongming Z Sun Zhanguo Z

Cancer biology & therapy 20191010 2

Circular RNAs (circRNAs) are a class of endogenous noncoding RNAs that are demonstrated to be potent regulators in the development of various types of human cancers, including non-small cell lung cancer (NSCLC). In the present study, the level of circRNA-HIPK3 were measured by Taq-man based quantitative real-time PCR (qRT-PCR) analysis in both NSCLC patient specimens and cells, which showed that circRNA-HIPK3 was upregulated in both NSCLC tissues and cell lines. Cell counting kit-8 (CCK-8), migr ...[more]

PMID: 31597523

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Project description:BackgroundFetal growth restriction (FGR) is a worldwide problem, and a major cause of perinatal morbidity. The precise molecular mechanisms involved in placental development and function during FGR remain poorly understood. Circular RNAs (circRNAs) are important biological molecules associated with disease pathogenesis. However, the role of circRNAs in FGR has not been well studied.MethodscircRNA expression profiles in placental tissues with and without FGR were identified by circRNA microarray. circRNA expression was verified by quantitative reverse-transcription PCR (RT-qPCR) assay. The effect of hsa_circ_0000848 and hsa-miR-6768-5p on HTR-8 cell apoptosis, migration, and invasion was evaluated. The association between hsa_circ_0000848 and hsa-miR-6768-5p was confirmed by dual luciferase activity and anti-AGO2 RNA immunoprecipitation (RIP) assays. Protein levels were examined via western blotting.ResultsRT-qPCR results showed that hsa_circ_0000848 expression was significantly down-regulated in FGR placenta. Hsa_circ_0000848 overexpression and hsa-miR-6768-5p inhibitor suppressed apoptosis, and promoted cell migration and invasion. In addition, hsa_circ_0000848 overexpression and hsa-miR-6768-5p inhibitor increased the protein abundance of BCL2, MMP2 and MMP9, and decreased the protein abundance of cleaved caspase-3, cleaved caspase-9, and BAX, whereas hsa_circ_0000848 knockdown caused the opposite effect. Moreover, a significant increase in hsa-miR-6768-5p expression and a negative correlation between hsa_circ_0000848 and hsa-miR-6768-5p were identified in the FGR tissues. Luciferase reporter and RIP assay results revealed binding of hsa-miR-6768-5p to hsa_circ_0000848. Furthermore, hsa-miR-6768-5p overexpression eliminated the effect of hsa_circ_0000848 overexpression in HTR-8 cells.Conclusionshsa_circ_0000848 expression is significantly down-regulated in the FGR placenta. hsa_circ_0000848 promotes trophoblast cell migration and invasion, and inhibits cell apoptosis via the sponging of hsa-miR-6768-5p. Our study provided a novel insight into mechanisms underlying the pathogenesis of FGR, as well as into new strategies for the treatment of FGR.

Project description:BACKGROUND:Recent evidences have shown that circular RNAs (circRNAs) are frequently dysregulated and play paramount roles in various cancers. circRNAs are abundant in central nervous system (CNS); however, few studies describe the clinical significance and role of circRNAs in gliomas, which is the most common and aggressive primary malignant tumor in the CNS. METHODS:A bioinformatics analysis was performed to profile and screen the dyregulated circRNAs during early neural development. Quantitative real-time PCR was used to detect the expression of circ-MAPK4 and target miRNAs. Glioma cells were transfected with circ-MAPK4 siRNAs, then cell proliferation, apoptosis, transwell assays, as well as tumorigenesis and TUNEL assays, were performed to examine effect of circ-MAPK4 in vitro and vivo. Biotinylated-circ-MAPK4 probe based pull-down assay was conducted to confirm the relationship between circ-MAPK4 and miR-125-3p. RESULTS:In this study, we identified a circRNA, circ-MAPK4 (has_circ_0047688), which was downregulated during early neural differentiation. In gliomas, circ-MAPK4 acted as an oncogene, was inversely upregulated and linked to clinical pathological stage of gliomas (P?<?0.05). Next, we verified that circ-MAPK4 promoted the survival and inhibited the apoptosis of glioma cells in vitro and in vivo. Furthermore, we proved that circ-MAPK4 was involved in regulating p38/MAPK pathway, which affected glioma proliferation and apoptosis. Finally, miR-125a-3p, a miRNA exhibited tumor-suppressive function through impairing p38/MAPK pathway, which was increased by inhibiting circ-MAPK4 and could be pulled down by circ-MAPK4. Inhibition of miR-125a-3p could partly rescue the increased phosphorylation levels of p38/MAPK and the elevated amount of apoptosis inducing by knockdown of circ-MAPK4. CONCLUSIONS:Our findings suggest that circ-MAPK4 is a critical player in glioma cell survival and apoptosis via p38/MAPK signaling pathway through modulation of miR-125a-3p, which can serve as a new therapeutic target for treatment of gliomas.

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Circular RNA HIPK3 induces cell proliferation and inhibits apoptosis in non-small cell lung cancer through sponging miR-149.

Publications

Circular RNA HIPK3 induces cell proliferation and inhibits apoptosis in non-small cell lung cancer through sponging miR-149.

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