Department of General Surgery, Affiliated Huashan Hospital of Fudan University, Shanghai, 200040, China.
Department of General Surgery, Affiliated Huashan Hospital of Fudan University, Shanghai, 200040, China.
Exp Cell Res. 2022 Jun 1;415(1):112973. doi: 10.1016/j.yexcr.2021.112973. Epub 2021 Dec 14.
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 up-regulate USP10 via competitively binding to miR-193b-5p. And USP10 could strengthen cell proliferative and migratory abilities through deubiquitinating PCNA.
肝细胞癌（HCC）是一种致命的恶性肿瘤，治疗选择有限。长链非编码 RNA（lncRNA）GASAL1 被发现在 HCC 中显著上调。然而，关于 GASAL1 在 HCC 中的作用研究仍然有限。我们的研究旨在探索 GASAL1 在 HCC 中的作用和机制。RT-qPCR 或 Western blot 用于检测 RNA 或蛋白质的表达。功能测定用于研究 GASAL1、USP10 和 PCNA 对 HCC 细胞的影响。机制测定用于探究 GASAL1、miR-193b-5p、USP10 和 PCNA 之间的关系。体内测定也用于确定 GASAL1 在 HCC 肿瘤生长和转移中的作用。根据收集的数据，GASAL1 在 HCC 细胞中表达较高，GASAL1 敲低导致细胞增殖和迁移受阻，以及肿瘤进展。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 可以通过去泛素化 PCNA 来促进 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 来上调 USP10。并且 USP10 可以通过去泛素化 PCNA 来增强细胞增殖和迁移能力。
