LncRNA F11-AS1 suppresses liver hepatocellular carcinoma progression by competitively binding with miR-3146 to regulate PTEN expression
LncRNA F11-AS1 suppresses liver hepatocellular carcinoma progression by competitively binding with miR-3146 to regulate PTEN expression
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DOI：
10.1002/jcb.29163
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发表时间：
2019-10-01
影响因子：
4
通讯作者：
Jiao, Xiaoqin
中科院分区：
文献类型：
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作者：
Du, Junkai;Chen, Mingyue;Jiao, Xiaoqin
越来越多的证据证明长链非编码RNA（lncRNA）参与癌症进展。 lncRNA的异常表达可能以多种方式介导癌症。肝细胞癌（LIHC）是肿瘤相关死亡的第三大原因。由于早期识别困难，LIHC的治疗效果远不能令人满意。 lncRNA 凝血因子 XI 反义 RNA 1 (F11-AS1) 在 LIHC 中表达不足，从而抑制 LIHC 进展。 F11-AS1可以与miR-3146结合并负向调节，而miR-3146可以与PTEN结合并负向调节。此外，F11-AS1 正向调节 PTEN 的信使 RNA 和蛋白水平。此外，miR-3146、F11-AS1 和 PTEN 都可以被 Ago2 抗体免疫沉淀，表明 RNA 诱导的沉默复合物的存在。因此，F11-AS1 通过充当 miR-3146 的竞争性内源 RNA 来介导 PTEN 表达。进一步的救援试验表明，F11-AS1 通过这种模式抑制 LIHC 进展。综上所述，F11-AS1通过与miR-3146竞争性结合调节PTEN表达来抑制LIHC进展。 F11-AS1/miR-3146/PTEN 轴是全新的。综上所述，结果表明 F11-AS1 可能作为 LIHC 的治疗靶点。
Accumulating evidence has proved that long noncoding RNAs (lncRNAs) are involved in cancer progression. The abnormal expression of lncRNAs might mediate cancer in various ways. Liver hepatocellular carcinoma (LIHC) is the third leading cause of tumor-related deaths. Due to the difficulty in its early recognition, the therapeutic outcomes of LIHC are far from satisfactory. The lncRNA Coagulation Factor XI Antisense RNA 1 (F11-AS1) is underexpressed in LIHC and suppresses LIHC progression in return. F11-AS1 can bind with and negatively regulate miR-3146, while miR-3146 can bind with and negatively regulate PTEN. Moreover, F11-AS1 positively regulates the messenger RNA and protein level of PTEN. Also, miR-3146, F11-AS1, and PTEN could all be immunoprecipitated by antibody against Ago2, indicating the existence of RNA-induced silencing complex. Therefore, F11-AS1 mediates PTEN expression by acting as competing endogenous RNA of miR-3146. Further rescue assays demonstrated that F11-AS1 suppressed LIHC progression via such pattern. To sum up, F11-AS1 suppresses LIHC progression by competitively binding with miR-3146 to regulate PTEN expression. The F11-AS1/miR-3146/PTEN axis is brand new. Taken together, the results indicate that F11-AS1 might serve as a therapeutic target of LIHC.