Critical role for the long non-coding RNA AFAP1-AS1 in the proliferation and metastasis of hepatocellular carcinoma. Lu Xu,Zhou Chuang,Li Renfeng,Liang Zhiwei,Zhai Wenlong,Zhao Longshuan,Zhang Shuijun Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine Increasing evidence has indicated that dysregulation of long non-coding RNAs (lncRNAs) can contribute to the progression and metastasis of human cancer, including HCC. Previous studies have shown that the lncRNA AFAP1-AS1 plays a critical role in cancer. However, the roles of AFAP1-AS1 in HCC remain to be determined. In the present study, AFAP1-AS1 was found to be increased in HCC tissues, and high AFAP1-AS1 expression was associated with tumor size, TNM stage, vascular invasion, and poor prognosis. Silencing of AFAP1-AS1 significantly reduced cell proliferation, clonal growth, cell migration, and invasion and increased apoptosis in vitro. Furthermore, AFAP1-AS1 silencing markedly reduced tumor growth in a murine allograft model in vivo. The results suggested that AFAP1-AS1 is important in HCC development and serves as a therapeutic target of HCC. 10.1007/s13277-016-4858-8

Bidirectional interaction of lncRNA AFAP1-AS1 and CRKL accelerates the proliferative and metastatic abilities of hepatocarcinoma cells. Abdul Sattar,Majid Abbasi,Wang Jinxia,Liu Qinlong,Sun Ming-Zhong,Liu Shuqing Journal of advanced research Actin filament-associated protein 1 antisense RNA 1 (AFAP1-AS1), a long non-coding RNA transcribed from the antisense strand of protein coding gene AFAP1, has attracted attention in cancer research. Despite, its biological function and regulatory mechanism in hepatocellular carcinoma still unknown. The present study revealed AFAP1-AS1 mediated hepatocarcinoma progression through targeting CRKL. The bidirectional interaction of AFAP1-AS1 and oncogenic protein CRKL, and the deregulation of AFAP1-AS1 effects on Ras, MEK and c-Jun activities were investigated in depth. AFAP1-AS1 was upregulated in surgical tumorous tissues from hepatocarcinoma patients compared with the paired paracancerous non-tumor liver tissues, and in hepatocarcinoma Huh7, HCCLM3 and HepG2 cell lines compared with LO2, a normal liver cell line. AFAP1-AS1 knockdown noticeably suppressed the proliferative, migratory and invasive properties, and the epithelial-mesenchymal transition (EMT) process of HepG2 and HCCLM3 through upregulating E-cadherin and downregulating N-cadherin and vimentin. CRKL knockdown reduced AFAP1-AS1 expression levels in HepG2 and HCCLM3 cells. AFAP1-AS1 suppression impaired CRKL expression in HepG2 and HCCLM3. AFAP1-AS1 level change was positively correlated with the expression level changes of Ras, MEK and c-Jun in mediating the invasiveness of hepatocarcinoma cells. Current work demonstrated AFAP1-AS1 to be an applicable progression indicator of hepatocarcinoma. AFAP1-AS1 probably promotes the proliferation, EMT progression and metastasis of hepatocarcinoma cells CRKL mediated Ras/MEK/c-Jun and cadherin/vimentin signaling pathways. AFAP1-AS1-CRKL bidirectional feedback signaling is worthy of further study on the monitoring, diagnosis and treatment of cancers. 10.1016/j.jare.2020.03.010

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. International journal of oncology 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. 10.3892/ijo.2016.3385