title: MicroRNA-424 inhibits Akt3/E2F3 axis and tumor growth in hepatocellular carcinoma.
abstract: 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.
authors: Liver Cancer Laboratory, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.|Department of Geratic Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
authors: Hao
authors: H
authors: Yang
authors: Liver Cancer Laboratory, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
authors: Wei
authors: W
authors: Zheng
authors: Liver Cancer Laboratory, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
authors: Xiao
authors: X
authors: Shuai
authors: Liver Cancer Laboratory, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
authors: Rui-Min
authors: RM
authors: Chang
authors: Liver Cancer Laboratory, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
authors: Lei
authors: L
authors: Yu
authors: Liver Cancer Laboratory, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
authors: Feng
authors: F
authors: Fang
authors: Liver Cancer Laboratory, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.|Department of Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
authors: Lian-Yue
authors: LY
authors: Yang
mesh_terms: D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015331:Cohort Studies; D018450:Disease Progression; D050699:E2F3 Transcription Factor / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D016016:Proportional Hazards Models; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D050699:E2F3 Transcription Factor; C098319:E2F3 protein, human; D019394:Ki-67 Antigen; C554214:MIRN424 microrna, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; C491754:AKT3 protein, human; D051057:Proto-Oncogene Proteins c-akt
keywords: Akt3; E2F3; hepatocellular carcinoma; miR-424; tumor growth