MiR-374b targets GATA3 to promote progression and development of glioblastoma via regulating SEMA3B

Abstract

In the present study, a series of experiments were conducted to explore the function of miR-374b and the regulatory relationship among miR-374b, GATA3 and SEMA3B in glioma. MiR-374b mimics and inhibitors were employed to regulate miR-374b expression. Besides, qRT-PCR assay was used for detecting the expression level of miR-374b, GATA3 and SEMA3B mRNAs. To verify the targeting relationship between miR-374b and GATA3, dual luciferase analysis was utilized. Moreover, chromatin immunoprecipitation (ChIP) assay was performed to identify the correlation GATA3 with SEMA3B. Furthermore, si1-GATA3, si2-GATA3 and pc-GATA3 were used to regulate GATA3 expression and pc-SEMA3B served for dysregulation the SEMA3B. For assessing the significance of miR374b alone or in cooperation with GATA3 or SEMA3B on cell viability, migration and apoptosis, CCK-8, transwell and FCM assay were also performed. We found that overexpression of miR-374b, which was identified in glioma tissues and cell lines (U251, LN-299 and GOS-3) promoted cell migration and enhanced cell viability but inhibited apoptosis in this study. Furthermore, GATA3 contributed to increase the cell viability and migration and decrease the apoptosis targeted by miR-374b as evidenced by dual luciferase assay. Moreover, GATA3 binding to the promoter of SEMA3B, involved in regulating SEMA3B, was revealed. Further, a series of studies demonstrated that miR-374b targeted GATA3 regulating SEMA3B and resulted in elevation of cell viability and migration but suppressed the apoptosis. However, the promotion effects of miR-374 in glioma process were reversed by co-transfecting pc-GATA3 or pc-SEMA3B. In conclusion, miR-374b promotes glioma process in vitro through suppressing SEMA3B via targeting GATA3. The result of this study provides an important clue to the optimal treatment schedule for glioblastoma.

miRNA-448 Regulates the Development of Glioblastoma (GBM) by Regulating Rho-Associated Protein Kinase 1

“…miR-365 was downregulated and suppressed cell proliferation and migration by downregulating PAX6 in GBM [ 7 ]. Conversely, miR-374b was upregulated and promoted GBM progression by suppressing GATA3 [ 8 ]. These studies suggest that dysregulation of miRNAs is involved in the pathogenesis of GBM.…”

Body temperature-dependent microRNA expression analysis in rats: rno-miR-374-5p regulates apoptosis in skeletal muscle cells via Mex3B under hypothermia

“…Mex3B is reportedly involved in the induction of apoptosis following cell stresses such as heat, cold shock, reactive oxygen species, and radiation 30 . Accordingly, overexpression of miR-374b-5p inhibited apoptosis and contributed to the elevation of cell survival 31 . Our results indicate that Mex3B directly or indirectly regulated Kras expression, which was accompanied by subsequent activation of downstream molecules such as Bcl2l1 in the Ras signalling pathway.…”

Non-Coding RNAs and Brain Tumors: Insights Into Their Roles in Apoptosis

“…Elevated levels of miR-374b are reported in glioma. MiR-374b is implicated in the glioma progression by regulating apoptosis via targeting GATA3 and SEMA3B ( Gao et al, 2019a ). Upregulation of decreased miR-378a-3p in glioblastoma decreased the expression of TSPAN17 and increased apoptosis ( Guo et al, 2019 ).…”