Zhu Liying, Yang Nenghong, Chen Juan, Zeng Tao, Yan Shaoying, Liu Yuyang, Yu Gangfeng, Chen Qiuxu, Du Guiqin, Pan Wei, Li Xing, Zhou Huihao, Huang Ailong, Tang Hua
Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
Department of Medical Laboratory, Guizhou Medical University, Guiyang, China.
Oncotarget. 2017 Jun 29;8(38):63724-63737. doi: 10.18632/oncotarget.18892. eCollection 2017 Sep 8.
Numerous studies have demonstrated that a class of long noncoding RNAs (lncRNAs) are dysregulated in hepatocellular carcinoma (HCC) and they are closely related with tumorigenesis. Our previous studies indicated that LINC00052 was a downregulated lncRNA in HCC and acted as a tumor suppressor gene. Using transcription microarray analysis, we found that knockdown of LINC00052 resulted in EPB41L3 downregulation. However, the function of EPB41L3 and the mechanism of LINC00052 downregulating EPB41L3 in HCC remain unclear. In this study, we found that overexpression of LINC00052 could upregulate the EPB41L3 expression and it might serve as a tumor suppressor gene in HCC. Database analysis showed that miR-452-5P could target LINC00052. The binding regions between LINC00052 and miR-452-5P were confirmed by luciferase assays. Moreover, LINC00052 inhibited cell malignant behavior by increasing miR-452-5P expression, suggesting that LINC00052 was negatively regulated by miR-452-5P. In addition, overexpression of miR-452-5P resulted in a decrease of EPB41L3 expression, suggesting that EPB41L3 was as a target of miR-452-5P. In conclusion, these results demonstrated that a novel pathway was mediated by LINC00052 in HCC.
大量研究表明，一类长链非编码RNA（lncRNAs）在肝细胞癌（HCC）中表达失调，且与肿瘤发生密切相关。我们之前的研究表明，LINC00052是HCC中一种表达下调的lncRNA，起到肿瘤抑制基因的作用。通过转录微阵列分析，我们发现敲低LINC00052会导致EPB41L3表达下调。然而，EPB41L3的功能以及LINC00052在HCC中下调EPB41L3的机制仍不清楚。在本研究中，我们发现LINC00052的过表达可上调EPB41L3的表达，并且它可能在HCC中作为肿瘤抑制基因发挥作用。数据库分析表明，miR - 452 - 5P可靶向LINC00052。荧光素酶报告基因实验证实了LINC00052与miR - 452 - 5P之间的结合区域。此外，LINC00052通过增加miR - 452 - 5P的表达来抑制细胞的恶性行为，这表明LINC00052受到miR - 452 - 5P的负调控。另外，miR - 452 - 5P的过表达导致EPB41L3表达降低，这表明EPB41L3是miR - 452 - 5P的靶标。总之，这些结果表明LINC00052在HCC中介导了一条新的信号通路。
