CircSTK39 suppresses the proliferation and invasion of bladder cancer by regulating the miR-135a-5p/NR3C2-mediated epithelial-mesenchymal transition signaling pathway

Cell Biol Toxicol. 2023 Aug;39(4):1815-1834. doi: 10.1007/s10565-022-09785-3. Epub 2022 Dec 20.

Abstract

Circular RNAs (circRNAs) serve as novel noncoding RNAs that have crucial functions in the development of tumors, including those from bladder cancer (BCa). However, the role and underlying molecular mechanism of circRNAs in mediating the epithelial-mesenchymal transition (EMT) processes in BCa have yet to be studied. In this research, we first found a novel circRNA, circSTK39 (termed as has_circ_0001079), which was a downregulated gene based on the results of high-throughput RNA sequencing. Subsequently, we determined that the expression of circSTK39 in BCa tissues and their cell lines was significantly reduced. In addition, lower circSTK39 expression was strongly related to a worse prognosis for BCa patients. Next, we detected the biological functions of circSTK39 by using loss and gain experiments in vitro and in vivo. Ectopic expression of circSTK39 decreased cell proliferation, colony formation, and invasion capacities, while circSTK39 knockdown prevented the above phenotypes. Mechanically, circSTK39 could sponge with miR-135a-5p, thus inhibiting NR3C2-mediated EMT processes in the BCa progression. In conclusion, our results revealed that circSTK39 inhibited EMT of BCa cells through the miR-135a-5p/NR3C2 axis and may provide promising biomarkers for the diagnosis or prospective therapeutic targets for BCa.

Keywords: Bladder cancer; Circular RNA; EMT; NR3C2; miR-135a-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Epithelial-Mesenchymal Transition
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • RNA, Circular* / metabolism
  • Receptors, Mineralocorticoid / genetics
  • Receptors, Mineralocorticoid / metabolism
  • Signal Transduction
  • Urinary Bladder Neoplasms* / genetics
  • Urinary Bladder Neoplasms* / pathology

Substances

  • MicroRNAs
  • NR3C2 protein, human
  • Receptors, Mineralocorticoid
  • RNA, Circular
  • MIRN135 microRNA, human
  • STK39 protein, human