MicroRNA-215-3p suppresses the growth and metastasis of cervical cancer cell via targeting SOX9

Eur Rev Med Pharmacol Sci. 2019 Jul;23(13):5628-5639. doi: 10.26355/eurrev_201907_18297.

Abstract

Objective: The aim of the current study was to investigate the potential roles of miR-215-3p in the progression of cervical cancer.

Patients and methods: The levels of miR-215-3p in both cervical cancer tissues and cell lines were detected using quantitative Real-time polymerase chain reaction (qRT-PCR) assay. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), colony formation, migration and invasion assays were applied to investigate the role of miR-215-3p on the growth and aggressiveness of cervical carcinoma SiHa cell. The expression of SRY-Box 9 (SOX9) was assessed by Western blotting assay. The Xenograft model and lung metastasis model were applied to reveal the impact of miR-215-3p on the growth and distant metastasis of cervical carcinoma cell in vivo. Moreover, miR-215-3p and a SOX9 siRNA were co-transfected into the SiHa cell to investigate the underlying mechanism of miR-215-3p-SOX9 on cervical cancer tumorigenesis.

Results: We used genome-wide gene expression analysis using clinical cervical cancer samples to identify that miR-215-3p was down-regulated in cervical cancer. We then collected 31 pairs of cervical cancer and the corresponding non-cancerous tissues to determine miR-215-3p level and indicated that miR-215-3p was significantly down-expressed in cervical cancer. Furthermore, the functional analysis suggested that over-expression of miR-215-3p suppressed the aggressiveness of SiHa cell, whereas down-regulation led to the opposite results. We identified SOX9 as a direct target of miR-215-3p, and its level was negatively related to the level of miR-215-3p in cervical carcinoma tissue. Up-regulation of SOX9 reversed the suppressive impact of miR-215-3p on cervical carcinoma cell, and down-regulation of SOX9 reversed the promote effects of miR-215-3p CONCLUSIONS: These findings showed the important role of the miR-215-3p/SOX9 axis in the progression of cervical carcinoma.

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Antagomirs / metabolism
  • Base Sequence
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation*
  • Down-Regulation
  • Female
  • Humans
  • Mice
  • Mice, Nude
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • RNA, Small Interfering / therapeutic use
  • SOX9 Transcription Factor / antagonists & inhibitors
  • SOX9 Transcription Factor / genetics
  • SOX9 Transcription Factor / metabolism*
  • Sequence Alignment
  • Transplantation, Heterologous
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / pathology*
  • Uterine Cervical Neoplasms / therapy

Substances

  • 3' Untranslated Regions
  • Antagomirs
  • MIRN215 microRNA, human
  • MicroRNAs
  • RNA, Small Interfering
  • SOX9 Transcription Factor
  • SOX9 protein, human