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GRSF1-mediated MIR-G-1 promotes malignant behavior and nuclear autophagy by directly upregulating TMED5 and LMNB1 in cervical cancer cells.

ABSTRACT: Emerging evidence has revealed that miRNAs could upregulate the expression levels of target genes. However, the molecular mechanism underlying upregulation of targets mediated by miRNAs remains unclear. In this study, we found a novel miRNA named MIR-G-1 by GRSF1-RNA immunoprecipitation (RIP)-deep sequencing, which could directly target and upregulate LMNB1 and TMED5 in a GRSF1-dependent manner in cervical cancer cells. In addition, upregulated MIR-G-1 in cervical cancer promoted a malignant phenotype in vitro and in vivo. TMED5 could interact with WNT7B and thus activated the canonical WNT-CTNNB1/β-catenin signaling pathway. MIR-G-1 mediated the activation of this pathway. Furthermore, MIR-G-1 promoted serum starvation-induced nuclear macroautophagy/autophagy, and accelerated taxol (TAX)-induced DNA-damage repair in cervical cancer cells. Collectively, these findings may provide a new insight into the upregulation mechanism and nuclear autophagy mediated by miRNAs and provide a potential biomarker for cervical cancer. Abbreviations: 3'UTR: 3' untranslated region; EMSA: electrophoretic mobility shift assay; EMT: epithelial-mesenchymal transition; GRSF1: G-rich RNA sequence binding factor 1; IF: immunofluorescence; IP: immunoprecipitation; IHC: immunohistochemistry; lnc: long noncoding; miRNA:microRNA; TAX: taxol; TMED5: transmembrane p24 trafficking protein 5.

SUBMITTER: Yang Z

PROVIDER: S-EPMC6526811 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundSevoflurane (Sev) has been reported to inhibit cancer development, and sevoflurane treatment in cancers is implicated with the deregulation of specific non-coding RNAs (ncRNAs). This study aimed to investigate the relationship between sevoflurane and circular RNA reelin (circRELN) in glioma.MethodsThe expression of circRELN, microRNA-1290 (miR-1290) and RAR-related orphan receptor A (RORA) was measured by quantitative real-time PCR (qPCR). Cell proliferative capacity was assessed by cell counting kit-8 (CCK-8) and colony formation assays. Cell apoptosis and cell cycle distribution were monitored by flow cytometry assay. Cell migration was assessed by wound healing assay and transwell assay, and cell invasion was assessed by transwell assay. The protein levels of matrix metalloproteinase-2 (MMP2), MMP9 and RORA were quantified by western blot. Tumor growth in vivo was assessed by Xenograft models. The binding relationship between miR-1290 and circRELN or RORA was verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay.ResultsWe found that circRELN expression was declined in glioma tissues and cells, while Sev treatment enhanced circRELN expression. In function, Sev notably inhibited glioma cell proliferation, migration and invasion and promoted apoptosis and cell cycle arrest, while circRELN knockdown reversed these effects. MiR-1290 served as a target of circRELN, and glioma cell malignant phenotypes recovered by circRELN knockdown were partly repressed by miR-1290 deficiency. In addition, RORA was a target of miR-1290, and glioma cell malignant phenotypes promoted by miR-1290 restoration were partly blocked by RORA overexpression. CircRELN regulated RORA expression by targeting miR-1290. In Xenograft models, Sev inhibited tumor growth by upregulating circRELN.ConclusionSev blocked the progression of glioma by increasing circRELN expression, and circRELN played roles in glioma partly by regulating the miR-1290/RORA network.

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GRSF1-mediated MIR-G-1 promotes malignant behavior and nuclear autophagy by directly upregulating TMED5 and LMNB1 in cervical cancer cells.

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