title: MicroRNA-34c-3p promotes cell proliferation and invasion in hepatocellular carcinoma by regulation of NCKAP1 expression.
abstract: OBJECTIVE
  Our previous miRNA profiling study indicated that microRNA-34c-3p (miR-34c-3p) was overexpressed and associated with survival in HCC. This study is aimed to confirm its clinical significance and explore the function and underlying mechanism of miR-34c-3p in HCC.
  
  
  METHODS
  We first evaluated miR-34c-3p expression and its relationship with prognosis in HCC patients. We then established stable HCC cell lines with miR-34c-3p overexpression and knockdown by the lentiviral packaging systems and performed the functional assays in vitro and in vivo, respectively. We next identified the target of miR-34c-3p by using microRNA target databases and dual-luciferase assay. Finally, the correlation between the expression of miR-34c-3p and the target gene was analyzed by immunohistochemistry and qRT-PCR in HCC tissues and hepatoma xenografts.
  
  
  RESULTS
  Overexpressed miR-34c-3p was confirmed in HCC tissues and significantly associated with poor survival of HCC patients. miR-34c-3p expression was also recognized as an independent risk factor for DFS and OS in multivariate analysis. Ectopic expression of miR-34c-3p significantly promotes the proliferation, colony formation, invasion and cell cycle regression of HCC cell lines. Knockdown of miR-34c-3p remarkably blocked hepatoma growth in the xenograft model. miRNA target databases and luciferase reporter assay showed that NCKAP1 was a direct target of miR-34c-3p in HCC cells and the high expression of NCKAP1 in HCC tissues is significantly correlated with low expression of miR-34c-3p and associated with a favorable prognosis of HCC patients.
  
  
  CONCLUSIONS
  The current study demonstrates that miR-34c-3p functions as a tumor promoter by targeting NCKAP1 that is associated with prognosis in HCC. miR-34c-3p and NCKAP1 may be new potential molecular targets for HCC therapy.
authors.affiliation: Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, China.|State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, China.|Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, China.|Department of General Surgery, Shenzhen Shajing Affiliated Hospital of Guangzhou Medical University, Shenzhen, 518100, China.
authors.forename: Cheng-Zuo
authors.initials: CZ
authors.lastname: Xiao
authors.affiliation: Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, China.|State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, China.|Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.affiliation: Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, China.|State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, China.
authors.forename: Zhi-Xing
authors.initials: ZX
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, China.
authors.forename: Mei-Yin
authors.initials: MY
authors.lastname: Zhang
authors.affiliation: Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, China.|State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, China.
authors.forename: Yong-Fa
authors.initials: YF
authors.lastname: Zhang
authors.affiliation: Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, China.|State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, China.
authors.forename: Jia-Hong
authors.initials: JH
authors.lastname: Wang
authors.affiliation: Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, China.|State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, China.|Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, China. wanghy@sysucc.org.cn.|Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, China. wanghy@sysucc.org.cn.
authors.forename: Hui-Yun
authors.initials: HY
authors.lastname: Wang
authors.affiliation: Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, China. guorp@sysucc.org.cn.|State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, China. guorp@sysucc.org.cn.|Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, China. guorp@sysucc.org.cn.
authors.forename: Rong-Ping
authors.initials: RP
authors.lastname: Guo
mesh_terms: D020413:3' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018572:Disease-Free Survival; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D008297:Male; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000502:physiology*; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D034622:RNA Interference; D047368:Tumor Burden
chemical_list: D020413:3' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; C484362:NCKAP1 protein, human
keywords: Cell proliferation; Hepatocellular carcinoma; MicroRNA-34c-3p; NCKAP1; Survival