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HLA-DQB1-AS1促进肝癌细胞增殖、抑制细胞凋亡并与ZRANB2蛋白结合

HLA-DQB1-AS1 Promotes Cell Proliferation, Inhibits Apoptosis, and Binds with ZRANB2 Protein in Hepatocellular Carcinoma.

作者信息

Long Jianwu, Liu Longfei, Zhou Xiaoyun, Lu Xianzhou, Qin Lei

机构信息

Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China.

Department of Hepatobiliary Surgery, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan 421002, China.

出版信息

J Oncol. 2022 May 11;2022:7130634. doi: 10.1155/2022/7130634. eCollection 2022.

DOI:10.1155/2022/7130634
PMID:35602293
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9117035/
Abstract

Major histocompatibility complex, class II, DQ beta 1 antisense RNA 1 (HLA-DQB1-AS1) conferred the susceptibility to hepatocellular carcinoma. Sustaining cell growth and resisting apoptosis are two hallmarks of hepatocellular carcinoma. The present study explored the role of HLA-DQB1-AS1 in the proliferation and apoptosis of hepatocellular carcinoma cells and investigated its downstream pathway. Colony formation assay was performed to assess cell proliferation. Cell apoptosis was assessed with the TdT-mediated dUTP nick end labeling method. HLA-DQB1-AS1 deficiency exerts antiproliferative and proapoptotic effects on hepatocellular carcinoma cells. Moreover, based on bioinformatic analysis combined with the results of RNA immunoprecipitation assay, HLA-DQB1-AS1 was revealed to bind with zinc finger RANBP2-type containing 2 (ZRANB2) protein. ZRANB2 was upregulated in hepatocellular carcinoma at a clinical and cellular level. HLA-DQB1-AS1 caused no significant effects on ZRANB2 mRNA and protein expression. ZRANB2 knockdown suppressed cell proliferation and enhanced cell apoptosis of hepatocellular carcinoma. Moreover, ZRANB2 overexpression rescued the anticancer effect of silenced HLA-DQB1-AS1 in hepatocellular carcinoma cells. In conclusion, HLA-DQB1-AS1 promotes cell proliferation and inhibits apoptosis in hepatocellular carcinoma by the interaction with ZRANB2 protein.

摘要

主要组织相容性复合体，II类，DQβ1反义RNA 1（HLA - DQB1 - AS1）赋予肝细胞癌易感性。维持细胞生长和抵抗细胞凋亡是肝细胞癌的两个标志。本研究探讨了HLA - DQB1 - AS1在肝癌细胞增殖和凋亡中的作用，并研究了其下游通路。采用集落形成试验评估细胞增殖。用TdT介导的dUTP缺口末端标记法评估细胞凋亡。HLA - DQB1 - AS1缺陷对肝癌细胞具有抗增殖和促凋亡作用。此外，基于生物信息学分析结合RNA免疫沉淀试验结果，发现HLA - DQB1 - AS1与含锌指RANBP2型2（ZRANB2）蛋白结合。ZRANB2在临床和细胞水平上在肝癌中上调。HLA - DQB1 - AS1对ZRANB2 mRNA和蛋白表达无显著影响。ZRANB2基因敲低抑制肝癌细胞增殖并增强细胞凋亡。此外，ZRANB2过表达挽救了沉默的HLA - DQB1 - AS1在肝癌细胞中的抗癌作用。总之，HLA - DQB1 - AS1通过与ZRANB2蛋白相互作用促进肝癌细胞增殖并抑制细胞凋亡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a63e/9117035/c877f8035b5c/JO2022-7130634.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a63e/9117035/4e0c7428cec8/JO2022-7130634.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a63e/9117035/d1798493faa3/JO2022-7130634.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a63e/9117035/fc7a5e763de1/JO2022-7130634.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a63e/9117035/41e53e2b13d8/JO2022-7130634.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a63e/9117035/148ad33d3e2a/JO2022-7130634.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a63e/9117035/c877f8035b5c/JO2022-7130634.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a63e/9117035/4e0c7428cec8/JO2022-7130634.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a63e/9117035/d1798493faa3/JO2022-7130634.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a63e/9117035/fc7a5e763de1/JO2022-7130634.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a63e/9117035/41e53e2b13d8/JO2022-7130634.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a63e/9117035/148ad33d3e2a/JO2022-7130634.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a63e/9117035/c877f8035b5c/JO2022-7130634.006.jpg

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