LncRNA GASAL1 promotes hepatocellular carcinoma progression by up-regulating USP10-stabilized PCNA
LncRNA GASAL1 promotes hepatocellular carcinoma progression by up-regulating USP10-stabilized PCNA
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LncRNA GASAL1 通过上调 USP10 稳定的 PCNA 促进肝细胞癌进展
DOI：
10.1016/j.yexcr.2021.112973
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发表时间：
2022-03-28
影响因子：
3.7
通讯作者：
Wang, Zhengxin
中科院分区：
文献类型：
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作者：
Shen, Conghuan;Li, Jianhua;Wang, Zhengxin
肝细胞癌（HCC）是一种致命的恶性肿瘤，治疗选择不足。长链非编码 RNA (lncRNA) GASAL1 在 HCC 中显着上调。然而，关于GASAL1在HCC中的作用的研究还很有限。我们的研究旨在探讨GASAL1在HCC中的作用和机制。进行 RT-qPCR 或蛋白质印迹来检查 RNA 或蛋白质的表达。进行功能测定以研究 GASAL1、USP10 和 PCNA 对 HCC 细胞的影响。进行机制分析以弄清楚 GASAL1、miR-193b-5p、USP10 和 PCNA 之间的关系。还采用体内测定来确定 GASAL1 在 HCC 肿瘤生长和转移中的作用。根据收集的数据，GASAL1在HCC细胞中表现出高表达，GASAL1敲低导致细胞增殖和迁移以及肿瘤进展受阻。一系列机制分析表明GASAL1可以海绵miR-193b-5p来提高USP10的表达。此外，USP10可以诱导PCNA去泛素化，促进HCC细胞生长。总之，GASAL1 在 HCC 中发挥致癌作用。 GASAL1 可以通过竞争性结合 miR-193b-5p 上调 USP10。 USP10可以通过去泛素化PCNA来增强细胞的增殖和迁移能力。
Hepatocellular carcinoma (HCC) is a fatal malignancy which has insufficient treatment options. Long non-coding RNA (lncRNA) GASAL1 was discovered to be conspicuously up-regulated in HCC. However, the study on the role of GASAL1 in HCC reamins limited. Our study aimed at exploring the role and mechanism of GASAL1 in HCC. RT-qPCR or Western blot was conducted to examine the expression of RNAs or proteins. Functional assays were carried out to investigate the impact of GASAL1, USP10, and PCNA on HCC cells. Mechanism assays were performed to fathom out the relationship among GASAL1, miR-193b-5p, USP10, and PCNA. In vivo assays were also employed to determine the role of GASAL1 in HCC tumor growth and metastases. According to the data collected, GASAL1 displayed a high expression in HCC cells and GASAL1 knockdown led to impeded cell proliferation and migration, as well as tumor progression. A series of mechanism analysis demonstrated GASAL1 could sponge miR-193b-5p to raise the expression of USP10. Moreover, USP10 could induce PCNA deubiquitination to promote HCC cell growth. To conclude, GASAL1 plays an oncogenic role in HCC. GASAL1 could upregulate USP10 via competitively binding to miR-193b-5p. And USP10 could strengthen cell proliferative and migratory abilities through deubiquitinating PCNA.