Comprehensive profiling of circRNAs and the tumor suppressor function of circHIPK3 in clear cell renal carcinoma

J Mol Histol. 2020 Jun;51(3):317-327. doi: 10.1007/s10735-020-09882-9. Epub 2020 May 14.

Abstract

Increasing evidence has indicated that circular RNAs (circRNAs) play a key role in the development and progression of diverse cancers, but their role in clear cell renal carcinoma (CCRCC) tumorigenesis is not well understood. In this study, we firstly performed comprehensive circRNA-seq from CCRCC tissues and pair-matched adjacent normal tissues. In total, 1184 circRNAs were dysregulated in human CCRCC tissues compared with those in adjacent normal tissues. We randomly selected four circRNAs, including circHIPK3 (circBase ID: hsa_circ_0000284), to test the circRNA-seq data in another 40 CCRCC tissues by quantitative real-time PCR (qRT-PCR). Furthermore, we found that circHIPK3 was downregulated in CCRCC tissues and cell lines. Overexpression of circHIPK3 effectively suppressed CCRCC cell invasion and migration in vitro, and inhibited CCRCC cell proliferation in vitro and in vivo. Moreover, bioinformatic analysis and luciferase reporter assay showed that circHIPK3 targeted miR-637 in CCRCC cells. Hence, CircHIPK3 may represent a tumor suppressor and target miR-637 in clear cell renal carcinoma.

Keywords: CircHIPK3; CircRNA; Circular RNA; Clear cell renal carcinoma; Renal carcinoma; miR-637.

MeSH terms

  • Animals
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / metabolism
  • Carcinoma, Renal Cell / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Kidney / pathology
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / pathology
  • Mice, Nude
  • MicroRNAs / genetics*
  • Protein Serine-Threonine Kinases / genetics*
  • RNA, Circular / genetics*
  • Up-Regulation
  • Xenograft Model Antitumor Assays

Substances

  • Intracellular Signaling Peptides and Proteins
  • MIRN637 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • HIPK3 protein, human
  • Protein Serine-Threonine Kinases