Expression of miR-122 mediated by adenoviral vector induces apoptosis and cell cycle arrest of cancer cells

Cancer Biol Ther. 2010 Apr 1;9(7):554-61. doi: 10.4161/cbt.9.7.11267. Epub 2010 Apr 1.

Abstract

Background: microRNA-122 (miR-122) plays an important role in both of hepatic physiology and pathology. Downregulation of miR-122 was reported in human primary hepatocellular carcinoma (HCC) and restoration of miR-122 could suppress the growth of cancer cells. In this study, we presented a novel strategy for cancer therapy based on gene transfer of miR-122 by adenoviral vector.

Methods: We generated a recombinant adenoviral vector expressing miR-122 (Ad-miR122). The miR-122 expression was measured by quantitative Real-Time PCR (qRT-PCR). Cell survival rate was determined by MTT assay.

Results: Our data showed that Ad-miR122 could express functional miR-122 in tumor cells at a high level. Infection of tumor cells with Ad-miR122 resulted in inhibition of growth of cancer cells originating from liver (HepG2, Hep3B, Huh7 and PLC/PRF/5), lung (NCI-H460) and uterine cervix (HeLa). This antitumor activity was related to the induction of apoptosis and/or cell cycle arrest in cancer cells. Infection with Ad-miR122 resulted in decreased expression of Bcl-W and CCNG1 in cancer cells.

Conclusion: The antitumor activity of Ad-miR122 was probably due to the induction of apoptosis and/or cell cycle arrest in cancer cells through inhibiting Bcl-W and/or CCNG1 expression. We concluded that expression of therapeutic microRNA, such as miR-122, via adenoviral vector is a promising strategy for cancer treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics*
  • Apoptosis Regulatory Proteins / antagonists & inhibitors
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism
  • Apoptosis*
  • Blotting, Western
  • Cell Cycle*
  • Cell Line, Tumor
  • Cell Proliferation
  • Cyclin G1 / antagonists & inhibitors
  • Cyclin G1 / genetics
  • Cyclin G1 / metabolism
  • Genetic Therapy
  • Genetic Vectors
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Humans
  • MicroRNAs / physiology*
  • Neoplasms / genetics*
  • Neoplasms / pathology
  • Neoplasms / therapy*
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Apoptosis Regulatory Proteins
  • BCL2L2 protein, human
  • CCNG1 protein, human
  • Cyclin G1
  • MIRN122 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins