CircAKT1 acts as a sponge of miR-338-3p to facilitate clear cell renal cell carcinoma progression by up-regulating CAV1

Biochem Biophys Res Commun. 2020 Nov 19;532(4):584-590. doi: 10.1016/j.bbrc.2020.08.081. Epub 2020 Sep 6.

Abstract

Circular RNAs (CircRNAs) have become a research focus for their important implication in tumorigenesis and cancer progression. This study intends to observe the function of circAKT1 in clear cell renal cell carcinoma (ccRCC) and its underlying molecular mechanism. In the present study, we confirmed the up-regulation of circAKT1 in ccRCC tissues and cells. High circAKT1 expression was positively associated with TNM stage, lymph node metastasis and predicted an adverse prognosis. Functionally, knockdown of circAKT1 suppressed cell proliferation, colony formation, migration, invasion and EMT in vitro. Mechanistic analysis uncovered that circAKT1 could act as a sponge for miR-338-3p to prevent the degradation of caveolin-1 (CAV1). Interestingly, the anti-neoplastic effect of circAKT1 knockdown on ccRCC was abated due to miR-338-3p down-regulation or CAV1 overexpression. To summarize, circAKT1 facilitated ccRCC progression at least partly by sequestering miR-338-3p to up-regulate CAV1 expression. Our findings raised the possibility of exploiting circAKT1 as a potential prognostic biomarker and therapeutic target in ccRCC.

Keywords: Caveolin-1; Clear cell renal cell carcinoma; circAKT1; miR-338–3p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / metabolism
  • Carcinoma, Renal Cell / mortality
  • Carcinoma, Renal Cell / pathology
  • Caveolin 1 / genetics*
  • Caveolin 1 / metabolism
  • Cell Line
  • Disease Progression
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / mortality
  • Kidney Neoplasms / pathology
  • MicroRNAs / metabolism*
  • Prognosis
  • Proto-Oncogene Proteins c-akt / genetics
  • RNA, Circular / metabolism*
  • Up-Regulation

Substances

  • CAV1 protein, human
  • Caveolin 1
  • MIRN338 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • AKT1 protein, human
  • Proto-Oncogene Proteins c-akt