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


CONCLUSIONS
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.
Xinyuan Institute of Medicine and Biotechnology, School of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, Zhejiang, China.
Leina
L
Ma
Jia
J
Liu
Junjie
J
Shen
Li
L
Liu
Jia
J
Wu
Wei
W
Li
Jingjing
J
Luo
Qing
Q
Chen
Cheng
C
Qian
D000256:Adenoviridae / Q000235:genetics*; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D056766:Cyclin G1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015316:Genetic Therapy; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D051017:Apoptosis Regulatory Proteins; C491073:BCL2L2 protein, human; C534702:CCNG1 protein, human; D056766:Cyclin G1; C531907:MIRN122 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins