Chu Jian, Geng Guangyong, Ai Xiaoming, Jia Wenbo, Wang Jinyi, Xu Bin, Kong Xiangxu, Kong Lianbao
Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), Nanjing, China.
J Gene Med. 2022 Feb;24(2):e3394. doi: 10.1002/jgm.3394. Epub 2021 Dec 22.
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Recent studies have demonstrated that lncRNAs play an important role in tumorigenesis. LINC01291 has been confirmed to be involved in the proliferation and migration of different cancers, although the function of LINC01291 in HCC is still unknown.
First, the expression of LINC01291 in 50 paired HCC tissues, adjacent normal tissues and HCC cell lines was measured by a quantitative real-time polymerase chain reaction. Then, the function of LINC01291 in HCC cell proliferation, migration and invasion was measured by colony formation, Cell Counting Kit-8 assays, wound healing assays and transwell assays. In addition, E-cadherin, N-cadherin, vimentin and oxidative stress-responsive 1 (OXSR1) protein expression levels were assessed via western blotting. Luciferase reporter assays were used to confirm the relationship between LINC01291 and miR-186-5p, as well as miR-186-5p and OXSR1 mRNA. Rescue assays and in vivo experiments further confirmed the LINC01291/miR-186-5p/OXSR1 axis in the progression of HCC.
LINC01291 was upregulated in both HCC tissues and cell lines. Knockdown of LINC01291 inhibited the proliferation, migration, invasion and epithelial-mesenchymal progression (EMT) of HCC cells. In addition, LINC01291 could overexpress OXSR1 by sponging miR-186-5p, and OXSR1 overexpression or miR-186-5p inhibition could rescue the effect of LINC01291 knockdown in YY-8103 cell lines. In addition, lentiviral sh-LINC01291 could effectively inhibit the growth of subcutaneous YY-8103 xenograft tumors, whereas the anticancer effect could be reversed by cotransfection with in-miR-186-5p or ov-OXSR1.
LINC01291 can promote the proliferation, migration, invasion and EMT of HCC cells via the miR-186-5p/OXSR1 axis, and sh-LINC01291 can inhibit tumor growth in a xenograft mouse model.
肝细胞癌（HCC）是全球最常见的癌症之一。最近的研究表明，长链非编码RNA（lncRNAs）在肿瘤发生中起重要作用。LINC01291已被证实参与不同癌症的增殖和迁移，尽管其在HCC中的功能仍不清楚。
首先，通过定量实时聚合酶链反应检测50对HCC组织、癌旁正常组织和HCC细胞系中LINC01291的表达。然后，通过集落形成、细胞计数试剂盒-8检测、伤口愈合检测和Transwell检测来测定LINC01291在HCC细胞增殖、迁移和侵袭中的功能。此外，通过蛋白质印迹法评估E-钙黏蛋白、N-钙黏蛋白、波形蛋白和氧化应激反应蛋白1（OXSR1）的蛋白表达水平。荧光素酶报告基因检测用于确认LINC01291与miR-186-5p之间的关系，以及miR-186-5p与OXSR1 mRNA之间的关系。挽救实验和体内实验进一步证实了LINC01291/miR-186-5p/OXSR1轴在HCC进展中的作用。
LINC01291在HCC组织和细胞系中均上调。敲低LINC01291可抑制HCC细胞的增殖、迁移、侵袭和上皮-间质转化（EMT）。此外，LINC01291可通过结合miR-186-5p来上调OXSR1的表达，OXSR1过表达或miR-186-5p抑制可挽救LINC01291敲低对YY-8103细胞系的影响。此外，慢病毒sh-LINC01291可有效抑制皮下YY-8103异种移植瘤的生长，而与in-miR-186-5p或ov-OXSR1共转染可逆转其抗癌作用。
LINC01291可通过miR-186-5p/OXSR1轴促进HCC细胞的增殖、迁移、侵袭和EMT，sh-LINC01291可抑制异种移植小鼠模型中的肿瘤生长。
