title: Long noncoding RNA AFAP1-AS1 indicates a poor prognosis of hepatocellular carcinoma and promotes cell proliferation and invasion via upregulation of the RhoA/Rac2 signaling.
abstract: It has been shown that long noncoding RNAs (lncRNAs) play a critical role in the regulation of cellular processes including cancer progression and metastasis. However, the biological functions and clinical significance of lncRNA AFAP1-AS1 in hepatocellular carcinoma (HCC) remain unclear. Expression of AFAP1-AS1 was analyzed in 78 HCC tissues by real-time PCR. The effect of AFAP1-AS1 on cell proliferation was examined by MTT assay, cell apoptosis was detected by flow cytometric analysis and cell invasion was determined by Transwell assay. RhoA/Rac2 signaling and downstream factors were verified by western blotting. HCC cells infected with si-AFAP1-AS1 were injected into nude mice to investigate the effect of AFAP1-AS1 on the tumorigenesis in vivo. We found that increased expression of AFAP1-AS1 was significantly correlated with pathological staging (P=0.024) and lymph-vascular space invasion (LVSI) in HCC patients (P=0.007). Multivariate analyses indicated that AFAP1-AS1 represented an independent predictor for overall survival of HCC (P=0.029). Further experiments showed that knockdown of AFAP1-AS1 by si-AFAP1-AS1 decreased the proliferation and invasion in vitro and in vivo, induced cell apoptosis and blocked cell cycle in S phase via inhibition of the RhoA/Rac2 signaling. Taken together, our findings indicate that AFAP1-AS1 may promote the HCC development through upregulation of RhoA/Rac2 signaling and provide a potential therapeutic target for HCC.
authors.affiliation: Department of General Surgery, Shanghai First People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P.R. China.
authors.forename: Jin-Yan
authors.initials: JY
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Shanghai First People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P.R. China.
authors.forename: Ming-Zhe
authors.initials: MZ
authors.lastname: Weng
authors.affiliation: Department of General Surgery, Shanghai First People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P.R. China.
authors.forename: Fang-Bin
authors.initials: FB
authors.lastname: Song
authors.affiliation: Department of General Surgery, Shanghai First People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P.R. China.
authors.forename: Yong-Gang
authors.initials: YG
authors.lastname: Xu
authors.affiliation: Department of General Surgery, Shanghai First People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P.R. China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of General Surgery, Shanghai First People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P.R. China.
authors.forename: Jun-Yi
authors.initials: JY
authors.lastname: Wu
authors.affiliation: Department of General Surgery, Shanghai First People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Qin
authors.affiliation: Department of General Surgery, Shanghai First People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Jin
authors.affiliation: Department of General Surgery, Shanghai First People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P.R. China.
authors.forename: Jun-Ming
authors.initials: JM
authors.lastname: Xu
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D009368:Neoplasm Transplantation; D011379:Prognosis; D062085:RNA, Long Noncoding / Q000235:genetics*; D015398:Signal Transduction; D016019:Survival Analysis; D015854:Up-Regulation; D020744:rac GTP-Binding Proteins / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*; D000097766:RAC2 GTP-Binding Protein
chemical_list: D062085:RNA, Long Noncoding; D020744:rac GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein; D000097766:RAC2 GTP-Binding Protein; C000605367:AFAP1-AS1 long noncoding RNA, human; C066737:RHOA protein, human