Ren Hua, Wei Zhi-Cheng, Sun Yan-Xia, Qiu Chun-Yan, Zhang Wen-Jue, Zhang Wei, Liu Tao, Che Xu
Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China.
Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China.
Front Oncol. 2021 Aug 27;11:714264. doi: 10.3389/fonc.2021.714264. eCollection 2021.
Long intergenic non-protein coding RNA 882 (LINC00882) are abnormally expressed in several tumors. Our research aimed to uncover the functions and the potential mechanisms of LINC00882 in hepatocellular carcinoma (HCC) progression.
RT-qPCR was applied to identify LINC00882 and miR-214-3p levels in HCC specimens and cells. Luciferase reporter was applied for the exploration of whether activating transcription factor 2 (ATF2) could bind to the promoter region of LINC00882. Cell proliferation, invasion, and migration were evaluated. tumor xenograft models were constructed to assess tumorigenicity. RT-PCR, Western blot and Luciferase reporter assays were conducted to examine the regulatory relationships among LINC00882, miR-214-3p and ATF2.
LINC00882 was markedly upregulated in HCC cells and clinical specimens. Additionally, ATF2 could bind directly to the LINC00882 promoter region and activate its transcription. Loss-of-function studies further demonstrated that LINC00882 knockdown inhibited proliferation, invasion, and migration of HCC cells. Mechanistically, LINC00882 adsorbed miR-214-3p, thus promoting the expressions of CENPM. Rescue assays demonstrated that functions of LINC00882 deficiency in HCC cells were reversed through suppressing miR-214-3p.
Our group identified a novel regulatory axis of ATF2/LINC00882/miR-214-3p/CENPM, which may provide potential therapeutic targets for HCC.
长链基因间非编码RNA 882（LINC00882）在多种肿瘤中异常表达。我们的研究旨在揭示LINC00882在肝细胞癌（HCC）进展中的功能及潜在机制。
应用逆转录定量聚合酶链反应（RT-qPCR）检测HCC标本和细胞中LINC00882和miR-214-3p的水平。应用荧光素酶报告基因实验探究激活转录因子2（ATF2）是否能与LINC00882的启动子区域结合。评估细胞增殖、侵袭和迁移能力。构建肿瘤异种移植模型以评估肿瘤发生能力。进行逆转录聚合酶链反应（RT-PCR）、蛋白质免疫印迹法（Western blot）和荧光素酶报告基因实验，以检测LINC00882、miR-214-3p和ATF2之间的调控关系。
LINC00882在HCC细胞和临床标本中显著上调。此外，ATF2可直接与LINC00882启动子区域结合并激活其转录。功能缺失研究进一步表明，敲低LINC00882可抑制HCC细胞的增殖、侵袭和迁移。机制上，LINC00882吸附miR-214-3p，从而促进着丝粒蛋白M（CENPM）的表达。挽救实验表明，通过抑制miR-214-3p可逆转LINC00882缺陷在HCC细胞中的功能。
我们的研究小组鉴定出一条新的ATF2/LINC00882/miR-214-3p/CENPM调控轴，这可能为HCC提供潜在的治疗靶点。
