Microcystin-LR promotes migration via the cooperation between microRNA-221/PTEN and STAT3 signal pathway in colon cancer cell line DLD-1

Ecotoxicol Environ Saf. 2019 Jan 15:167:107-113. doi: 10.1016/j.ecoenv.2018.09.065. Epub 2018 Oct 9.

Abstract

Previous researches have reported that microcystin-LR (MC-LR) contributes to the progression of multiple types of carcinomas including colon cancer; however, the underlying molecular mechanisms remain unclear and require in-depth investigation. Here, the colon cell line DLD-1 was arranged for the analysis by the microRNA microarray which was associated with the cancer metastasis after MC-LR exposure. 31 human microRNAs were differentially expressed, including miR-221, which targeted 3'-UTR of PTEN mRNA and PTEN level was down-regulated by MC-LR treatment. Besides, MC-LR also induced the phosphorylation of STAT3, which can be reversed by adding miR-221 inhibitor and PTEN expression plasmid. Furthermore, miR-221 inhibitor, STAT3 siRNA and PTEN expression plasmid could reverse the effects of MC-LR induced migration with the accumulation of β-catenin in nuclei. In conclusion, our study suggested that MC-LR promoted the progression of colon carcinoma, at least in part, by regulating the expression miR-221, PTEN and STAT3 phosphorylation, which offers a novel perspective to understand the connection between MC-LR and colon cancer.

Keywords: Colon cancer cell; MicroRNA-221/PTEN; Microcystin-LR; Migration; STAT3; β-catenin.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • Down-Regulation
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Marine Toxins
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics*
  • Microcystins / pharmacology*
  • PTEN Phosphohydrolase / genetics*
  • PTEN Phosphohydrolase / metabolism
  • Phosphorylation / drug effects
  • RNA, Messenger / metabolism
  • RNA, Small Interfering
  • STAT3 Transcription Factor / genetics*
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction / drug effects
  • Up-Regulation
  • beta Catenin / metabolism

Substances

  • CTNNB1 protein, human
  • Enzyme Inhibitors
  • MIRN221 microRNA, human
  • Marine Toxins
  • MicroRNAs
  • Microcystins
  • RNA, Messenger
  • RNA, Small Interfering
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • beta Catenin
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • cyanoginosin LR