LncRNA SOX2-OT regulates miR-192-5p/RAB2A axis and ERK pathway to promote glioblastoma cell growth

Cell Cycle. 2021 Oct;20(19):2010-2020. doi: 10.1080/15384101.2021.1965722. Epub 2021 Sep 1.

Abstract

Glioblastoma (GBM) is the most frequent tumor in the central nervous system. Long non-coding RNAs (lncRNAs) have been widely accepted as essential participators in cancer progression. Nonetheless, the specific role and mechanism of lncRNA SRY-box transcription factor 2 overlapping transcript (SOX2-OT) in GBM have not been studied. We evaluated expression levels of SOX2-OT, miR-192-5p and Ras-related protein Rab-2A (RAB2A) in GBM cells via qRT-PCR. To investigate the roles of SOX2-OT in GBM cells, CCK-8, JC-1, EdU, and western blot assays were performed. The connection among SOX2-OT, miR-192-5p and RAB2A in GBM cells was explored through pull down, luciferase reporter, and RIP assays. Western blot and qRT-PCR were employed to analyze the activity of extracellular-signal-regulated kinase (ERK) signaling pathway. SOX2-OT expression was higher in GBM cell lines than in normal cells. SOX2-OT knockdown repressed proliferation and promoted apoptosis of GBM cells. Mechanism assays revealed that SOX2-OT could sponge miR-192-5p. Moreover, RAB2A was certified to be the target gene of miR-192-5p. Overexpression of RAB2A reversed the repressive function of SOX2-OT knockdown on GBM cell growth. Furthermore, SOX2-OT activated ERK signaling pathway in GBM cells. SOX2-OT regulated miR-192-5p/RAB2A axis and ERK pathway to promote GBM cell growth.

Keywords: Glioblastoma; RAB2A; SOX2-OT; miR-192-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Gene Expression Regulation, Neoplastic
  • Glioblastoma* / pathology
  • Humans
  • MAP Kinase Signaling System / genetics
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • SOXB1 Transcription Factors / genetics
  • SOXB1 Transcription Factors / metabolism

Substances

  • MIRN192 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • SOX2 protein, human
  • SOXB1 Transcription Factors
  • Extracellular Signal-Regulated MAP Kinases

Grants and funding

This research was funded by Natural Science Foundation of Ningbo (No.2019A610283); Ningbo Municipal Bureau of Science and Technology (No.2014C50089; No.2018A10054)