Long non-coding RNA TDRG1 aggravates colorectal cancer stemness by binding with miR-873-5p to upregulate PRKAR2

Environ Toxicol. 2022 Oct;37(10):2366-2374. doi: 10.1002/tox.23602. Epub 2022 Jun 22.

Abstract

The effects of long non-coding RNA TDRG1 have been established in several tumors; however, its roles in colorectal cancer (CRC) progression are never been found. Here, we found that TDRG1 level was upregulated in CRC cells compared to that in normal colon epithelial cells. Additionally, TDRG1 level was remarkably upregulated in 3D non-adherent spheres derived from the parental CRC cells. Further in vitro and in vivo revealed that TDRG1 knockdown suppressed the stemness of CRC cells. What's more, combined with bioinformatics analysis, luciferase reporter and RNA pull down experiments showed that TDRG1 could bind to miR-873-5p, downregulated its level and thus increase the expression of PRKAR2. Finally, it was shown that TDRG1 functioned through the miR-873-5p/PRKAR2 axis. This study demonstrated a novel TDRG1/miR-873-5p/PRKAR2 signaling in CRC progression.

Keywords: MiR-873-5p; PRKAR2; Stemness; colorectal cancer; long non-coding RNA.

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Colorectal Neoplasms* / metabolism
  • Cyclic AMP-Dependent Protein Kinase Type II / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism

Substances

  • MIRN873 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • Cyclic AMP-Dependent Protein Kinase Type II