miR-613 suppresses renal cell carcinoma proliferation, invasion and migration by regulating the AXL/AKT pathway

Exp Biol Med (Maywood). 2023 Feb;248(4):281-292. doi: 10.1177/15353702231151962. Epub 2023 Feb 27.

Abstract

In the last few decades, microRNAs (miRNAs) are possible to effectively control and treat cancer. However, the function of miR-613 in renal cell carcinoma (RCC) is not very clear up to now. Here, the direction of this research was to investigate the influence of miR-613 for the proliferation, invasion and migration of RCC, and the underlying molecular mechanism. First, the mRNA and protein expression levels of miR-613 were determined in RCC tissues and cancer cells (786-O and ACHN). Using bioinformatics and literature review, anexelekto (AXL), as the target of miR-613 in renal cell carcinoma, was screened. Phenotype experiment and mechanism experiment illustrated the targeting relationship between miR-613 and AXL in cancer cells. Furthermore, a rescue assay with AXL overexpression was performed to make a profound study whether miR-613 disturbs RCC proliferation, invasion, and migration through direct regulation of AXL. Finally, through experiment in vivo, we observe the influence of miR-613 overexpression for tumor. These results were as follows. The present findings proved, in RCC, that the production of miR-613 was at a low level. Except for this point, this current research confirmed, in RCC cells, that the upregulation of miR-613 can control proliferation, metastasis, and invasion by reducing AXL levels and controlling the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway.

Keywords: AKT; AXL; RCC; invasion; miR-613; migration; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Renal Cell* / genetics
  • Carcinoma, Renal Cell* / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kidney Neoplasms* / genetics
  • Kidney Neoplasms* / pathology
  • MicroRNAs* / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism

Substances

  • MicroRNAs
  • MIRN613 microRNA, human
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • AXL protein, human