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. 2020 Dec;43(6):1035-1048.
doi: 10.1007/s13402-020-00533-5. Epub 2020 Sep 25.

NF-κB-mediated miR-650 plays oncogenic roles and activates AKT/ERK/NF-κB pathways by targeting RERG in glioma cells

Shiguang Jin  1   2 , Xueping Li  3 , Yan Dai  1 , Cheng Li  1 , Daxin Wang  4
Affiliations

NF-κB-mediated miR-650 plays oncogenic roles and activates AKT/ERK/NF-κB pathways by targeting RERG in glioma cells

Shiguang Jin et al. Cell Oncol (Dordr). 2020 Dec.

Abstract

Purpose: Glioma is the most common cancer in the central nervous system and has a high mortality rate. Despite advances that have been made in the treatment of glioma, its prognosis still remains poor. Dysregulation of miRNAs has been reported in many cancers, including glioma. Here, we set out to assess the role of miR-650 in glioma, including its diagnostic and therapeutic potential.

Methods: miR-650 and RAS-like estrogen-regulated growth inhibitor (RERG) expression levels were analyzed using qRT-PCR in primary glioma tissues and cell lines. Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine, colony formation, Western blotting, scratch wound healing, Transwell, adhesion, autophagy, immunofluorescence, luciferase reporter, electrophoretic mobility shift, tumor xenograft and flow cytometry assays were employed to investigate the mechanisms underlying the effect of miR-650 and RERG on glioma development.

Results: miR-650 was found to be up-regulated in glioma tissues and cell lines compared to non-cancerous brain tissues and neural progenitor cells, respectively. We also found that miR-650 promoted cell proliferation, migration and invasion in glioma cells, and enhanced glioma tumor formation and growth in vivo. We identified and validated RERG as a direct target of miR-650. RERG was shown to act as a tumor suppressor in glioma cells, and its suppressor roles were rescued by miR-650. We found that nuclear factor (NF)-κB bound to the promoter of miR-650 and enhanced its expression. PH domain and leucine rich repeat protein phosphatase 2 (PHLPP2), as a co-factor of the RERG/PHLPP2 complex, mediated miR-650-induced activation of the protein kinase B/extracellular-signal-regulated kinase/NF-κB signaling pathways.

Conclusions: Our data revealed novel functional roles for miR-650 in glioma development and may provide new avenues for future clinical applications.

Keywords: AKT/ERK; Glioma; NF-κB; PHLPP2; RERG; miR-650.

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