STAT4-mediated down-regulation of miR-3619-5p facilitates stomach adenocarcinoma by modulating TBC1D10B

Cancer Biol Ther. 2020 Jul 2;21(7):656-664. doi: 10.1080/15384047.2020.1754690. Epub 2020 May 13.

Abstract

Background: MicroRNAs (miRNAs) as the subtype of non-coding RNAs are revealed to be crucial players in cellular activities. It has been reported that miR-3619-5p functions as a tumor inhibitor in several cancers. However, the connection between miR-3619-5p and stomach adenocarcinoma (STAD) remains to be discovered.

Aim of the study: The purpose of the study is to figure out the role and molecular regulation mechanism of miR-3619-5p in STAD.

Methods: The expression of miR-3619-5p was evaluated via qRT-PCR analysis. Gain-of-function experiments demonstrated the effects of miR-3619-5p on cellular functions. The upper-stream transcription factor STAT4 and downstream target gene TBC1D10B of miR-3619-5p were identified by bioinformatic analysis. The binding and interaction between the indicated molecules were verified by RNA pull-down and luciferase reporter assays.

Results: The expression of miR-3619-5p was prominently down-regulated in STAD cells and tissues. MiR-3619-5p suppresses cell proliferation, migration, invasion and tumor growth in STAD. Further, STAT4 bound with miR-3619-5p promoter and inhibited its transcription. MiR-3619-5p was also recognized to modulate STAD progression through the regulation of downstream target gene TBC1D10B.

Conclusion: STAT4-mediated miR-3619-5p controls STAD carcinogenesis and progression through modulating TBC1D10B expression, which may provide a novel insight for researching the STAD-related molecular mechanism.

Keywords: STAT4; TBC1D10B; miR-3619-5p; stomach adenocarcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Animals
  • Cell Line, Tumor
  • Disease Progression
  • Down-Regulation
  • Heterografts
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • STAT4 Transcription Factor / genetics
  • STAT4 Transcription Factor / metabolism*
  • Signal Transduction
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology
  • Transfection

Substances

  • Adaptor Proteins, Signal Transducing
  • MIRN-3619 microRNA, human
  • MicroRNAs
  • STAT4 Transcription Factor
  • STAT4 protein, human
  • TBC1D10B protein, human

Grants and funding

This work was supported by the key Projects in Anhui Colleges and Universities Natural Science Foundation (No. KJ2018A0250); the Key Research and Development Program Projects in Anhui Province (No. 201904a07020034); Funding of “Peak” Training Program for Scientific Research of Yijishan Hospital; Wannan Medical College (No. GF2019G19)