Hsa_circ_0014717 is downregulated in colorectal cancer and inhibits tumor growth by promoting p16 expression

Biomed Pharmacother. 2018 Feb:98:775-782. doi: 10.1016/j.biopha.2018.01.015. Epub 2018 Jan 5.

Abstract

Circular RNAs (circRNAs) represent a novel class of non-coding RNAs that may regulate gene expression in eukaryotes. Nevertheless, their potential functions in human malignancies are still largely unknown. The aim of this study was to explore the expression of hsa_circ_0014717 in colorectal cancer (CRC) and its role involving in tumor growth. We found that hsa_circ_0014717 was downregulated in CRC tissues and cell lines, and was significantly correlated with TNM stage, distal metastasis and poor overall survival of CRC patients as well. Moreover, our gain-of-function analysis further showed that hsa_circ_0014717 overexpression could significantly suppress CRC cell proliferation and colony formation, as well as induce cell cycle G0/G1 phase arrest in vitro and inhibit xenograft tumor growth in vivo. In addition, hsa_circ_0014717 could upregulate the expression of cell cycle inhibitory protein p16. Besides, p16 knockdown could reverse hsa_circ_0014717 mediated growth inhibition of CRC cells. Taken together, hsa_circ_0014717 acts as a potential tumor suppressor that inhibits CRC growth, partly at least, through upregulating p16 expression. Furthermore, our present study may provide a promising therapeutic target for CRC patients.

Keywords: Cell cycle; Cell proliferation; Circular RNA; Colorectal cancer; Hsa_circ_0014717; p16.

MeSH terms

  • Animals
  • Carcinogenesis / genetics
  • Carcinogenesis / pathology
  • Cell Cycle / genetics
  • Cell Cycle Checkpoints / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Colorectal Neoplasms / diagnosis
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology*
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism*
  • Down-Regulation / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Gene Knockdown Techniques
  • Humans
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • Middle Aged
  • Prognosis
  • RNA / genetics*
  • RNA / metabolism
  • RNA, Circular
  • Tumor Stem Cell Assay
  • Up-Regulation / genetics

Substances

  • Cyclin-Dependent Kinase Inhibitor p16
  • RNA, Circular
  • RNA