Department of Second Liver Disease, Qingdao Sixth People's Hospital, No.9, Fushun Road, Sifang District, Qingdao City, Shandong, 266000, China.
Department of Blood Purification, Qingdao Sixth People's Hospital, No.9, Fushun Road, Sifang District, Qingdao City, Shandong, 266000, China.
Biochem Biophys Res Commun. 2019 Jan 8;508(2):472-479. doi: 10.1016/j.bbrc.2018.11.092. Epub 2018 Nov 30.
Accumulating evidence suggest that long noncoding RNAs (lncRNAs) are dysregulated in various tumors and serve as crucial regulators in biological processes. Based on The Cancer Genome Atlas (TCGA) database, upregulation of CASC11 was associated with the low overall survival rate of patients with Hepatocellular carcinoma (HCC). However, the function and mechanism of lncRNA CASC11 in the progression of HCC remain unclear. Therefore, we further analyzed the expression pattern and biological role of CASC11 in HCC. CASC11 was found to be overexpressed in HCC tissues and cell lines and predicted a poor prognosis. Loss of CASC11 function efficiently suppressed cell migration, invasion and epithelial-mesenchymal transition (EMT). The mechanism which led to the upregulation of CASC11 was investigated. CASC11 was found to be activated by the transcription factor STAT3. Mechanically, the enhancer of zeste homolog 2 (EZH2) was found to be a binding partner of CASC11. Moreover, CASC11 epigenetically silenced PTEN by binding with EZH2. Finally, rescue assays were conducted to make confirmation. The present results revealed that CASC11 may be potential therapeutic target in HCC.
越来越多的证据表明，长链非编码 RNA（lncRNA）在各种肿瘤中失调，并作为生物过程中的关键调节剂。基于癌症基因组图谱（TCGA）数据库，CASC11 的上调与肝细胞癌（HCC）患者的总生存率降低有关。然而，lncRNA CASC11 在 HCC 进展中的功能和机制仍不清楚。因此，我们进一步分析了 CASC11 在 HCC 中的表达模式和生物学作用。CASC11 在 HCC 组织和细胞系中过度表达，并预测预后不良。CASC11 功能的丧失有效地抑制了细胞迁移、侵袭和上皮-间充质转化（EMT）。我们研究了导致 CASC11 上调的机制。发现转录因子 STAT3 激活了 CASC11。机制上，发现增强子结合锌指蛋白 2（EZH2）是 CASC11 的结合伙伴。此外，CASC11 通过与 EZH2 结合，表观遗传地下调了 PTEN。最后进行了挽救实验来验证。这些结果表明，CASC11 可能是 HCC 的潜在治疗靶点。
