期刊
ONCOTARGET
卷 6, 期 29, 页码 27736-27750出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.4811
关键词
hepatocellular carcinoma; miR-424; Akt3; E2F3; tumor growth
资金
- National Keystone Basic Research Program of China [2009CB521801]
- Clinical Subjects' Key Project of Ministry of Health
- National Science & Technology Major Projects [2009ZX09103-681, 2012ZX10002012-011]
- National Nature Science Foundation of China [81172018, 81272395]
- Nature Science Foundation of Xiangya [2013Q07]
By comparing the expression profiles of miRNAs in different subtypes of HCC, we identified miR-424 as a HCC related miRNA. We found that the expression of miR-424 was significantly decreased in HCC tissues and six liver cancer cell lines. Significantly, its expression levels were correlated with tumor size, multiple nodules, vein invasion, TNM stage and overall survival of HCC. We showed that up-regulated miR-424 suppressed HCC cell proliferation in vivo and in vitro. Multi-pathway reporter arrays suggested that miR-424 suppressed the pRb-E2F pathway. Consistently, Akt3 and E2F3 were identified as the targets of miR-424 as evidenced by that ectopic miR-424 expression suppressed Akt3 and E2F3 expressions. Silencing Akt3 and E2F3 by siRNA pheno-copied the effect of ectopic miR-424 on HCC growth. Whereas, overexpression of Akt3 and E2F3 attenuated the effect of miR-424 on HCC growth. Together, our data demonstrated a tumor suppressor role for miR-424 in HCC development and progression with therapeutic implications. The strong correlation of miR-424 expression with HCC patient survival suggests that miR-424 could be a valuable biomarker for HCC prognosis.
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