MicroRNA-122 overexpression promotes apoptosis and tumor suppressor gene expression induced by microcystin-leucine arginine in mouse liver

Int J Environ Health Res. 2022 Oct;32(10):2123-2134. doi: 10.1080/09603123.2021.1946489. Epub 2021 Jun 28.

Abstract

Microcystin-leucine arginine (MC-LR), an important hepatoxin, has the effect of promoting hepatocarcinogenesis. MicroRNA-122 (miR-122), an important tumor suppressor in liver, plays an important role in promoting cell apoptosis. Previous studies found that the expression of miR-122 was reduced after MC-LR exposure in liver. In this study, C57BL/6 mice were exposed to saline, negative control agomir, and MC-LR with or without miR-122 agomir transfection. The results indicated that MC-LR promoted the expressions of tumor suppressor genes and decreased the expressions of anti-apoptotic proteins B cell lymphoma-2 (Bcl-2) and Bcl-2-like 2 (Bcl-w), causing hepatocyte apoptosis. Under MC-LR exposure, miR-122 agomir transfection could further increase the expressions of tumor suppressor genes and the release of cytochrome-c (Cyt-c) and decrease the expressions of Bcl-2 and Bcl-w. In conclusion, miR-122 reduction can mitigate MC-LR-induced apoptosis to a certain extent, which in turn, it is likely to have contributed to MC-LR-induced hepatocarcinogenesis.

Keywords: MC-LR; apoptosis; miR-122.

MeSH terms

  • Animals
  • Apoptosis
  • Apoptosis Regulatory Proteins / metabolism
  • Apoptosis Regulatory Proteins / pharmacology
  • Arginine / metabolism
  • Arginine / pharmacology
  • Cytochromes / metabolism
  • Cytochromes / pharmacology
  • Genes, Tumor Suppressor
  • Leucine / metabolism
  • Leucine / pharmacology
  • Liver
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs* / genetics
  • Microcystins* / metabolism
  • Microcystins* / toxicity
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / pharmacology

Substances

  • Apoptosis Regulatory Proteins
  • Cytochromes
  • MicroRNAs
  • Microcystins
  • Mirn122 microRNA, mouse
  • Proto-Oncogene Proteins c-bcl-2
  • Arginine
  • Leucine