miR-138-5p inhibits proliferation and invasion in kidney renal clear cell carcinoma by targeting SINA3 and regulation of the Notch signaling pathway

J Clin Lab Anal. 2021 Nov;35(11):e23766. doi: 10.1002/jcla.23766. Epub 2021 Sep 29.

Abstract

Background: The function of miR-138-5p as an oncogenic factor has been reported in certain cancers. This study was performed to analyze the potential involvement of miR-138-5p in kidney renal clear cell carcinoma (KIRC).

Methods: The Cancer Genome Atlas (TCGA) database was used to explain the expression of miR-138-5p in cancer and paired non-cancer tissues of KIRC patients. Subsequently, miR-138-5p expression in KIRC tissues and cell lines, as well as that in normal tissues and normal renal tubular epithelial cell line, was detected. Artificial overexpressing of miR-138-5p was applied to observe its effect on the biological behaviors of KIRC cells. The target mRNA of miR-138-5p, SIN3A, was predicted and validated. Altered expression of miR-138-5p and SIN3A was introduced to confirm their functions in KIRC proliferation and invasion.

Results: We showed that miR-138-5p was down-regulated in tumor tissues of KIRC patients comparing to adjacent healthy tissues and linked to dismal prognosis in patients. miR-138-5p could hinder KIRC proliferation and invasion, while artificial overexpression of SIN3A led to reversed trends. SIN3A was a target mRNA of miR-138-5p. miR-138-5p and SIN3A together affect the activation of the Notch signaling pathway.

Conclusion: This study evidenced that up-regulated miR-138-5p inhibits proliferation and invasion of KIRC cells involving the transcription of SIN3A and the following regulation of the Notch signaling pathway.

Keywords: Notch signaling pathway; SIN3A; invasion; kidney renal clear cell carcinoma; miR-138-5p; proliferation.

MeSH terms

  • Carcinoma, Renal Cell* / genetics
  • Carcinoma, Renal Cell* / metabolism
  • Carcinoma, Renal Cell* / mortality
  • Carcinoma, Renal Cell* / pathology
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Humans
  • Kidney Neoplasms* / genetics
  • Kidney Neoplasms* / metabolism
  • Kidney Neoplasms* / mortality
  • Kidney Neoplasms* / pathology
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Neoplasm Invasiveness / genetics
  • Receptors, Notch / genetics*
  • Receptors, Notch / metabolism
  • Signal Transduction / genetics
  • Sin3 Histone Deacetylase and Corepressor Complex / genetics*
  • Sin3 Histone Deacetylase and Corepressor Complex / metabolism

Substances

  • MIRN138 microRNA, human
  • MicroRNAs
  • Receptors, Notch
  • SIN3A transcription factor
  • Sin3 Histone Deacetylase and Corepressor Complex