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

• Published in: International journal of oncology Vol. 48; no. 4; pp. 1590 - 1598
• Main Authors: ZHANG, JIN-YAN, WENG, MING-ZHE, SONG, FANG-BIN, XU, YONG-GANG, LIU, QI, WU, JUN-YI, QIN, JUN, JIN, TAO, XU, JUN-MING
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01.04.2016; Spandidos Publications; Spandidos Publications UK Ltd
• Subjects: AFAP1-AS1; Angiogenesis; Animals; Apoptosis; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - pathology; Cell cycle; Cell growth; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cellular signal transduction; Cloning; Development and progression; Female; Gene expression; Gene Expression Regulation, Neoplastic; Genetic aspects; growth; Health aspects; Hep G2 Cells; hepatocellular carcinoma; Hepatoma; Humans; Immunoglobulins; invasion; Kinases; Liver cancer; Liver cirrhosis; Liver Neoplasms - genetics; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; long noncoding RNA; Male; Medical prognosis; Metastasis; Mice; Multivariate analysis; Neoplasm Transplantation; Prognosis; Proteins; rac GTP-Binding Proteins - metabolism; RAC2 GTP-Binding Protein; rhoA GTP-Binding Protein - metabolism; RNA, Long Noncoding - genetics; Signal Transduction; Studies; Survival Analysis; Tumorigenesis; Up-Regulation; United States > US
• ISSN: 1019-6439; 1791-2423
• DOI: 10.3892/ijo.2016.3385

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.