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 via 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.

肌动蛋白丝相关蛋白1反义RNA 1（AFAP1-AS1）是从蛋白编码基因AFAP1的反义链转录而来的长的非编码RNA，在癌症研究中引起了人们的注意。尽管如此，其在肝细胞癌中的生物学功能和调控机制仍然未知。本研究揭示了AFAP1-AS1通过靶向CRKL介导的肝癌进展。深入研究了AFAP1-AS1与致癌蛋白CRKL的双向相互作用以及AFAP1-AS1对Ras，MEK和c-Jun活性的抑制作用。与成对的癌旁非肿瘤肝组织相比，肝癌患者的手术肿瘤组织中的AFAP1-AS1上调；与正常肝细胞系LO2相比，在肝癌Huh7，HCCLM3和HepG2细胞系中AFAP1-AS1上调。通过上调E-钙黏着蛋白和下调N-钙黏着蛋白和波形蛋白，AFAP1-AS1敲低显着抑制了HepG2和HCCLM3的增殖，迁移和侵袭特性以及上皮-间质转化（EMT）过程。CRKL抑制降低了HepG2和HCCLM3细胞中AFAP1-AS1的表达水平。AFAP1-AS1抑制削弱HepG2和HCCLM3中的CRKL表达。AFAP1-AS1水平的变化与Ras，MEK和c-Jun的表达水平的变化在介导肝癌细胞侵袭性中呈正相关。当前的工作表明AFAP1-AS1是肝癌的适用进展指标。AFAP1-AS1可能促进肝癌细胞的增殖，EMT进程和转移 通过上调E-cadherin和下调N-cadherin和vimentin来实现HepG2和HCCLM3的上皮-间质转化（EMT）过程。CRKL抑制降低了HepG2和HCCLM3细胞中AFAP1-AS1的表达水平。AFAP1-AS1抑制削弱HepG2和HCCLM3中的CRKL表达。AFAP1-AS1水平的变化与Ras，MEK和c-Jun的表达水平的变化在介导肝癌细胞侵袭性中呈正相关。当前的工作表明AFAP1-AS1是肝癌的适用进展指标。AFAP1-AS1可能促进肝癌细胞的增殖，EMT进程和转移 通过上调E-cadherin和下调N-cadherin和vimentin来实现HepG2和HCCLM3的上皮-间质转化（EMT）过程。CRKL抑制降低了HepG2和HCCLM3细胞中AFAP1-AS1的表达水平。AFAP1-AS1抑制削弱HepG2和HCCLM3中的CRKL表达。AFAP1-AS1水平的变化与Ras，MEK和c-Jun的表达水平的变化在介导肝癌细胞侵袭性中呈正相关。当前的工作表明AFAP1-AS1是肝癌的适用进展指标。AFAP1-AS1可能促进肝癌细胞的增殖，EMT进程和转移 AFAP1-AS1抑制削弱HepG2和HCCLM3中的CRKL表达。AFAP1-AS1水平的变化与Ras，MEK和c-Jun的表达水平的变化在介导肝癌细胞侵袭性中呈正相关。当前的工作表明AFAP1-AS1是肝癌的适用进展指标。AFAP1-AS1可能促进肝癌细胞的增殖，EMT进程和转移 AFAP1-AS1抑制削弱HepG2和HCCLM3中的CRKL表达。AFAP1-AS1水平的变化与Ras，MEK和c-Jun的表达水平的变化在介导肝癌细胞侵袭性中呈正相关。当前的工作表明AFAP1-AS1是肝癌的适用进展指标。AFAP1-AS1可能促进肝癌细胞的增殖，EMT进程和转移通过CRKL介导的R​​as / MEK / c-Jun和钙粘蛋白/波形蛋白信号通路。AFAP1-AS1-CRKL双向反馈信号在癌症的监测，诊断和治疗方面值得进一步研究。