LINC00174 down-regulation decreases chemoresistance to temozolomide in human glioma cells by regulating miR-138-5p/SOX9 axis

Hum Cell. 2020 Jan;33(1):159-174. doi: 10.1007/s13577-019-00281-1. Epub 2019 Nov 12.

Abstract

Temozolomide (TMZ) is one of the most common drugs selected for glioma chemotherapy, but the therapeutic effect of glioma treatment is usually limited due to its resistance. Long non-coding RNA (lncRNA) is gradually found to be a vital regulator in numerous physiological and pathological processes. Lately, it was revealed that LINC00174 could promote CRC cell growth. However, the function and potential regulatory manner of LINC00174 in glioma remain unclear. Our results demonstrated that the expression level of LINC00174 was higher in glioma tissues, and LINC00174 down-regulation could remarkably prevent cell proliferation and promote cell apoptosis in both glioma cells and TMZ-resistant glioma cells. Mechanistic studies revealed that LINC00174 can sponge microRNA-138-5p (miR-138-5p) and down-regulate its expression, thereby up-regulating the protein level of miR-138-5p's target, sex-determining region Y (SRY)-box9 protein (SOX9). Additionally, in vivo experiments revealed that LINC00174 shRNA can serve as a tumor suppressor through down-regulating SOX9 in glioma. In this study, a novel established regulatory way of LINC00174/miR-138-5p/SOX9 axis was systematically studied, which may provide a new manner for glioma therapy.

Keywords: Cell proliferation; Glioma; LINC00174; SOX9; miR-138-5p.

MeSH terms

  • Brain Neoplasms / genetics*
  • Drug Resistance, Neoplasm / genetics
  • Glioma / genetics*
  • Humans
  • MicroRNAs / genetics*
  • SOX9 Transcription Factor / genetics*
  • Temozolomide*

Substances

  • MIRN135 microRNA, human
  • MicroRNAs
  • SOX9 Transcription Factor
  • SOX9 protein, human
  • Temozolomide