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长链非编码 RNA LINC00924 通过海绵吸附 miR-6755-5p 上调 NDRG2 抑制乙型肝炎病毒相关肝细胞癌中的上皮-间充质转化。

LncRNA LINC00924 upregulates NDRG2 to inhibit epithelial-mesenchymal transition via sponging miR-6755-5p in hepatitis B virus-related hepatocellular carcinoma.

机构信息

Department of Ultrasound, People's Hospital of Dongxihu District, Wuhan, Hubei, China.

Department of Infectious Disease, People's Hospital of Dongxihu District, Wuhan, Hubei, China.

出版信息

J Med Virol. 2022 Jun;94(6):2702-2713. doi: 10.1002/jmv.27578. Epub 2022 Jan 23.

DOI:10.1002/jmv.27578
PMID:34997970
Abstract

Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) is a life-threatening cancer. Long noncoding RNAs participate in HBV-related HCC progression. Based on the bioinformatics analysis, LINC00924 downregulation is positively related to unfavorable outcomes in patients with HBV-related HCC. Herein, we detected the biological functions and regulatory system of LINC00924 in HCC. The LINC00924 downregulation in HBV-related HCC tissues and cells was revealed by reverse transcription-quantitative polymerase chain reaction. Functionally, as Transwell assays and western blotting indicated, LINC00924 elevation inhibited HCC cell invasion and epithelial-mesenchymal transition (EMT). The binding site between LINC00924 and miR-6755-5p was determined by luciferase reporter assays. miR-6755-5p was confirmed to target NDRG2. miR-6755-5p upregulation decreased NDRG2 messenger RNA (mRNA) and protein levels. The mRNA and protein levels of NDRG2 were downregulated in tissues and cells. NDRG2 knockdown attenuated the inhibition induced by LINC00924 overexpression on invasion and EMT of HCC cells. In summary, LINC00924 increases NDRG2 expression to inhibit EMT by targeting miR-6755-5p in HBV-related HCC.

摘要

乙型肝炎病毒(HBV)相关肝细胞癌(HCC)是一种危及生命的癌症。长链非编码 RNA 参与 HBV 相关 HCC 的进展。基于生物信息学分析,LINC00924 的下调与 HBV 相关 HCC 患者的不良结局呈正相关。在此,我们检测了 LINC00924 在 HCC 中的生物学功能和调控系统。通过逆转录定量聚合酶链反应揭示了 LINC00924 在 HBV 相关 HCC 组织和细胞中的下调。功能上,如 Transwell 分析和 Western blot 所示,LINC00924 的上调抑制了 HCC 细胞的侵袭和上皮-间充质转化(EMT)。通过荧光素酶报告基因测定确定了 LINC00924 与 miR-6755-5p 之间的结合位点。miR-6755-5p 被证实靶向 NDRG2。miR-6755-5p 的上调降低了 NDRG2 的信使 RNA(mRNA)和蛋白水平。NDRG2 的 mRNA 和蛋白水平在组织和细胞中均下调。NDRG2 的敲低减弱了 LINC00924 过表达对 HCC 细胞侵袭和 EMT 的抑制作用。总之,LINC00924 通过靶向 miR-6755-5p 增加 NDRG2 的表达来抑制 HBV 相关 HCC 中的 EMT。

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