Ye Shanting, Ni Yong
Graduate School of Guangzhou Medical University, Guangzhou, China.
Department of Hepatobiliary Surgery, Shenzhen Second People's Hospital, Shenzhen, China.
Front Mol Biosci. 2021 Apr 9;8:649976. doi: 10.3389/fmolb.2021.649976. eCollection 2021.
Hepatocellular carcinoma (HCC) is among the major causes of cancer-related mortalities globally. Long non-coding RNAs (LncRNAs), as epigenetic molecules, contribute to malignant tumor incidences and development, including HCC. Although LncRNA SNHG9 is considered an oncogene in many cancers, the biological function and molecular mechanism of SNHG9 in HCC are still unclear. We investigated the effects of lncRNA SNHG9 on the methylation of glutathione S-transferase P1 (GSTP1) and the progression of HCC. Histological data analysis, CRISPR-dCas9, and cytological function experiment were used to study the expression level and biological function of SNHG9 in HCC. There was an upregulated expression of SNHG9 in HCC, which was associated with shorter disease-free survival. Knockdown of SNHG9 can inhibit cell proliferation, block cell cycle progression, and inhibit cell migration and invasion by upregulating GSTP1. LncRNA SNHG9 recruits methylated enzymes (DNMT1, DNMT3A, and DNMT3B) to increase GSTP1 promoter methylation, a common event in the development of HCC. Inhibition of lncRNA SNHG9 demethylates GSTP1, which prevents HCC progression, presents a promising therapeutic approach for HCC patients.
肝细胞癌(HCC)是全球癌症相关死亡的主要原因之一。长链非编码RNA(LncRNAs)作为表观遗传分子,参与包括HCC在内的恶性肿瘤的发生和发展。尽管LncRNA SNHG9在许多癌症中被认为是一种癌基因,但其在HCC中的生物学功能和分子机制仍不清楚。我们研究了lncRNA SNHG9对谷胱甘肽S-转移酶P1(GSTP1)甲基化及HCC进展的影响。采用组织学数据分析、CRISPR-dCas9和细胞学功能实验研究SNHG9在HCC中的表达水平和生物学功能。HCC中SNHG9表达上调,这与无病生存期缩短有关。敲低SNHG9可通过上调GSTP1抑制细胞增殖、阻断细胞周期进程并抑制细胞迁移和侵袭。LncRNA SNHG9招募甲基化酶(DNMT1、DNMT3A和DNMT3B)以增加GSTP1启动子甲基化,这是HCC发生过程中的常见事件。抑制lncRNA SNHG9可使GSTP1去甲基化,从而阻止HCC进展,为HCC患者提供了一种有前景的治疗方法。