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

被引:139
|
作者
Zhang, Jin-Yan [1 ]
Weng, Ming-Zhe [1 ]
Song, Fang-Bin [1 ]
Xu, Yong-Gang [1 ]
Liu, Qi [1 ]
Wu, Jun-Yi [1 ]
Qin, Jun [1 ]
Jin, Tao [1 ]
Xu, Jun-Ming [1 ]
机构
[1] Shanghai Jiao Tong Univ, Sch Med, Dept Gen Surg, Shanghai Peoples Hosp 1, 11th Floor,Room 2,100 Haining Rd, Shanghai 200080, Peoples R China
基金
中国国家自然科学基金;
关键词
long noncoding RNA; AFAP1-AS1; hepatocellular carcinoma; growth; invasion; ZESTE HOMOLOG 2; HIGH EXPRESSION; RHOA; CANCER; METASTASIS; RECURRENCE; SURVIVAL; RECEPTOR; ENHANCER; PATHWAY;
D O I
10.3892/ijo.2016.3385
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:1590 / 1598
页数:9
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