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长链非编码 RNA HAND2-AS1 通过上调 SOCS5 抑制 JAK-STAT 通路来抑制肝癌细胞增殖和迁移。

lncRNA HAND2-AS1 Inhibits Liver Cancer Cell Proliferation and Migration by Upregulating SOCS5 to Inactivate the JAK-STAT Pathway.

机构信息

Department of Infectious Diseases, Laiwu People's Hospital, Laiwu, China.

Radiotherapy Department, and Laiwu People's Hospital, Laiwu, China.

出版信息

Cancer Biother Radiopharm. 2020 Mar;35(2):143-152. doi: 10.1089/cbr.2019.2958.

DOI:10.1089/cbr.2019.2958
PMID:32155348
Abstract

lncRNA HAND2 antisense RNA 1 (HAND2-AS1) is consistently well recognized to suppress multiple tumors, while its function was uncertified in liver cancer. qRT-PCR analysis and TCGA database discovered the expression in liver cancer. CCK-8 and Transwell migration assay demonstrated the impact of HAND2-AS1 on cell proliferation and migration. Bioinformatic analysis and luciferase reporter assay were utilized to monitor the binding between HAND2-AS1 or SOCS5 mRNA and miR-3118. The function of SOCS5 on inactivating the JAK-STAT pathway was confirmed through Western blot assays. Rescue experiments unmasked that HAND2-AS1-mediated SOCS5 affected cell proliferation and migration through the JAK-STAT pathway in liver cancer. The authors discovered the downregulated HAND2-AS1 in liver cancer cells. HAND2-AS1 augmentation apparently impaired the capacity of liver cancer viability, proliferation, and migration. Cytoplasmic HAND2-AS1 directly bound to miR-3118 and released SOCS5, leading to upregulation of SOCS5. Next, the negative regulator role of SOCS5 in the adjusting JAK-STAT pathway was reconfirmed in this study. HAND2-AS1 enhanced inactivation of the JAK-STAT pathway through sponging miR-3118 and facilitating SOCS5 to retard cell proliferation and migration in liver cancer.

摘要

长链非编码 RNA HAND2 反义 RNA1(HAND2-AS1)被一致认为能抑制多种肿瘤,而其在肝癌中的功能尚未得到证实。qRT-PCR 分析和 TCGA 数据库发现了 HAND2-AS1 在肝癌中的表达。CCK-8 和 Transwell 迁移实验表明 HAND2-AS1 对细胞增殖和迁移有影响。生物信息学分析和荧光素酶报告实验用于监测 HAND2-AS1 或 SOCS5 mRNA 与 miR-3118 的结合。通过 Western blot 实验证实了 SOCS5 通过抑制 JAK-STAT 通路来失活。通过拯救实验揭示了 HAND2-AS1 介导的 SOCS5 通过 JAK-STAT 通路影响肝癌细胞的增殖和迁移。作者发现肝癌细胞中 HAND2-AS1 下调。HAND2-AS1 的增加明显削弱了肝癌细胞的活力、增殖和迁移能力。细胞质 HAND2-AS1 直接与 miR-3118 结合并释放 SOCS5,导致 SOCS5 上调。在这项研究中,SOCS5 在调节 JAK-STAT 通路中的负调控作用得到了进一步证实。HAND2-AS1 通过海绵吸附 miR-3118 增强了 JAK-STAT 通路的失活,促进 SOCS5 抑制肝癌细胞增殖和迁移。

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