Hsa_circ_0136666 promotes the proliferation and invasion of colorectal cancer through miR-136/SH2B1 axis

J Cell Physiol. 2019 May;234(5):7247-7256. doi: 10.1002/jcp.27482. Epub 2018 Oct 28.

Abstract

Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. Currently, an increasing evidence showed that circular RNAs (circRNAs) play important roles in tumor progression. However, the effects and underlying mechanisms of circRNAs in CRC progression remain unclear. In the present study, through circRNA high-throughput sequencing and quantitative real-time polymerase chain reaction, we identified that hsa_circ_0136666 was significantly overexpressed in CRC tissues and cell lines. High hsa_circ_0136666 expression was associated with poor overall survival of patients with CRC. In vitro function assays showed that hsa_circ_0136666 inhibition suppressed CRC cell proliferation, migration, invasion, and arrested CRC cells in the G0/G1 phase. Furthermore, we showed that hsa_circ_0136666 inhibition reduced CRC cell growth in vivo. Mechanistically, we revealed that hsa_circ_0136666 could increase SH2B1 expression via competitively binding miR-136 in CRC cells. In addition, SH2B1 overexpression could reverse the effects of hsa_circ_0136666 inhibition on CRC cell progression. In conclusion, our data suggested that hsa_circ_0136666 could promote CRC cell progression via the miR-136/SH2B1 axis, elucidating a novel approach to improve the effectiveness of CRC treatment.

Keywords: SH2B1; colorectal cancer (CRC); hsa_circ_0136666; miR-136.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Cell Cycle Checkpoints
  • Cell Movement*
  • Cell Proliferation*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology
  • Gene Expression Regulation, Neoplastic
  • HCT116 Cells
  • HT29 Cells
  • Humans
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness
  • RNA, Circular / genetics
  • RNA, Circular / metabolism*
  • Signal Transduction
  • Up-Regulation

Substances

  • Adaptor Proteins, Signal Transducing
  • MIRN136 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • SH2B1 protein, human