Downregulation of microRNA miR-520h by E1A contributes to anticancer activity.
The leading cause of death in cancer patients is cancer metastasis, for which there is no effective treatment. MicroRNAs (miRNA) have been shown to play a significant role in cancer metastasis through regulation of gene expression. The adenovirus type 5 E1A (E1A) is associated with multiple tumor-suppressing activities including the inhibition of metastasis, and E1A gene therapies have been tested in several clinical trials. However, the mechanisms involved in E1A-mediated tumor-suppressing activities are not yet completely defined. Here, we showed that E1A downregulated the expression of the miRNA miR-520h, which was critical for E1A-mediated cancer cell mobility and in vitro invasion activity. In addition, we identified a signal cascade, namely, E1A-->miRNA-520h-->PP2A/C-->IkappaB kinase-->NF-kappaB-->Twist, in which E1A inhibited the expression of Twist through downregulation of miR-520h and the signal cascade. Our results indicated a functional link between miR-520h and tumorigenicity/invasive ability and provided a new insight into the role of E1A-mediated miRNA regulation in tumor suppression. Therefore, the results identified a new cascade of E1A-mediated tumor suppression activity via downregulation of miRNA-520h expression.
Su
Jen-Liang
JL
Graduate Institute of Cancer Biology, College of Medicine, China Medical University and Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan.
Chen
Poshen B
PB
Chen
Ya-Huey
YH
Chen
Shang-Chih
SC
Chang
Yi-Wen
YW
Jan
Yi-Hua
YH
Cheng
Xiaoyun
X
Hsiao
Michael
M
Hung
Mien-Chie
MC
D017500:Adenovirus E1A Proteins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement; D015536:Down-Regulation; D005260:Female; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D035683:MicroRNAs / Q000502:physiology*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D054648:Protein Phosphatase 2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000378:metabolism
D017500:Adenovirus E1A Proteins; D000970:Antineoplastic Agents; D035683:MicroRNAs; D016328:NF-kappa B; D012333:RNA, Messenger; D051879:Twist-Related Protein 1; D054648:Protein Phosphatase 2