Circular RNA circ_001842 plays an oncogenic role in renal cell carcinoma by disrupting microRNA-502-5p-mediated inhibition of SLC39A14

J Cell Mol Med. 2020 Sep;24(17):9712-9725. doi: 10.1111/jcmm.15529. Epub 2020 Jul 30.

Abstract

Renal cell carcinoma (RCC) is a common urologic malignancy, and up to 30% of RCC patients present with locally advanced or metastatic disease at the time of initial diagnosis. Increasing evidence suggests that circular RNAs (circRNAs) serve as genomic regulatory molecules in various human cancers. Our initial in silico microarray-based analysis identified that circRNA circ_001842 was highly expressed in RCC. Such up-regulation of circ_001842 in RCC was experimentally validated in tissues and cell lines using RT-qPCR. Thereafter, we attempted to identify the role of circ_001842 in the pathogenesis of RCC. Through a series of gain- and loss-of function assays, cell biological functions were examined using colony formation assay, Transwell assay, annexin V-FITC/PI-labelled flow cytometry and scratch test. A high expression of circ_001842 in tissues was observed as associated with poor prognosis of RCC patients. circ_001842 was found to elevate SLC39A14 expression by binding to miR-502-5p, consequently resulting in augmented RCC cell proliferation, migration and invasion, as well as EMT in vitro and tumour growth in vivo. These observations imply the involvement of circ_001842 in RCC pathogenesis through a miR-502-5p-dependent SLC39A14 mechanism, suggesting circ_001842 is a potential target for RCC treatment.

Keywords: SLC39A14; circular RNA circ_001842; microRNA-502-5p; renal cell carcinoma.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / pathology
  • Cation Transport Proteins / genetics*
  • Cell Line
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / pathology
  • Male
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics*
  • Middle Aged
  • Oncogenes / genetics*
  • Prospective Studies
  • RNA, Circular / genetics*
  • Up-Regulation / genetics

Substances

  • Cation Transport Proteins
  • MIRN502 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • SLC39A14 protein, human