The lncRNA TUG1 promotes cell growth and migration in colorectal cancer via the TUG1-miR-145-5p-TRPC6 pathway

Biochem Cell Biol. 2021 Apr;99(2):249-260. doi: 10.1139/bcb-2020-0017. Epub 2020 Sep 27.

Abstract

Colorectal cancer (CRC) is the third-most prevalent malignant tumor. Taurine upregulated gene 1 (TUG1), a long non-coding RNA (lncRNA), is reportedly involved in the physiological and pathological processes of CRC. However, the role of TUG1 in the progression of CRC and its underlying mechanisms are largely unknown. Here, we measured the expression of TUG1 in clinical samples from CRC patients and found that the expression level of TUG1 was higher in CRC tissues compared with the normal adjacent tissues. We then performed knockdown of TUG1 with siRNAs in two CRC cell lines and found that TUG1 knockdown inhibited the viability, proliferation, and migration of CRC cells, and reduced the ability of CRC cells to form subcutaneous tumors. Furthermore, we discovered that TUG1 affects the cellular processes in CRC cells by sponging miR-145-5p. We further found that miR-145-5p inhibits the expression of the protein-encoding gene Transient Receptor Potential Cation Channel Subfamily C Member 6 (TRPC6), and that overexpression of TRPC6 restored the inhibitory role of miR-145-5p in CRC cells. In conclusion, we have demonstrated that TUG1 exerts its role by modulating the TUG1-miR-145-5p-TRPC6 regulatory axis, thus revealing a novel molecular mechanism for the effects of TUG1 in the progression of CRC. Our data indicate that the TUG1-miR-145-5p-TRPC6 signaling pathway could serve as a target for the diagnosis and treatment of CRC.

Keywords: ARNlnc TUG1; TRPC6; cancer colorectal; colorectal cancer; lncRNA-TUG1; miR-145-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Movement
  • Cell Proliferation
  • Cell Survival
  • Cells, Cultured
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • TRPC6 Cation Channel / genetics
  • TRPC6 Cation Channel / metabolism*

Substances

  • MIRN145 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • TRPC6 Cation Channel
  • TRPC6 protein, human
  • TUG1 long noncoding RNA, human