The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, 533000, Guang Xi, China.
People's Hospital of Baise, Baise, 533000, Guang Xi, China.
Clin Transl Oncol. 2023 Jun;25(6):1793-1804. doi: 10.1007/s12094-023-03077-w. Epub 2023 Feb 3.
Long noncoding RNA (lncRNAs) GMDS-AS1 has been reported as a tumor regulator in tumor growth and metastasis, but its effect in hepatocellular carcinoma (HCC) remains unclear. ESET, a histone H3K9 methyl-transferase, is involved in epigenomic regulation of tumor progression in multiple cancers. However, the correlation between ESET and lncRNA in HCC is less reported.
Quantitative real-time PCR (qRT-PCR) was taken to determine the expression of ESET and GMDS-AS1. Western blot was taken to determine the target protein levels of ESET and GMDS-AS1. Online database and bioinformatics analysis were used to screen abnormally expressed genes. Luciferase assay was performed to confirm the binding of GMDS-AS1 and PSMB1. Ki67 and Edu were used for evaluated the proliferation of tumor cells. ChIP assay was performed to verify the relationship between H3K9me1 and lncRNA GMDS-AS1 promoter. Transwell was taken to determine the migration and invasion ability of tumor cells. CCK-8 was used for determining the viability of tumor cells. Flow cytometry was performed to detect the cell cycle of tumor cells.
The expression of GMDS-AS1 was decreased and the expression of ESET was increased in HCC. GMDS-AS1 inhibition contributed to tumor development, and this effect was closely related to epigenetic inhibition of GMDS-AS1 by ESET. PSMB1, a downstream target of GMDS-AS1, promoted the tumor proliferation and was negatively regulated by GMDS-AS1.
Our result demonstrates anti-tumorigenic traits of lncRNA GMDS-AS1 in HCC and explains its pattern of regulation mediated by ESET. Our work unmasked an essential role of GMDS-AS1 in HCC progression and detected a novel pathway for ESET to promote HCC.
长链非编码 RNA（lncRNA）GMDS-AS1 已被报道在肿瘤生长和转移中作为肿瘤调节剂，但在肝细胞癌（HCC）中的作用尚不清楚。ESET，一种组蛋白 H3K9 甲基转移酶，参与多种癌症中肿瘤进展的表观基因组调控。然而，ESET 与 HCC 中 lncRNA 的相关性报道较少。
采用实时定量 PCR（qRT-PCR）检测 ESET 和 GMDS-AS1 的表达。采用 Western blot 检测 ESET 和 GMDS-AS1 的靶蛋白水平。利用在线数据库和生物信息学分析筛选异常表达基因。采用荧光素酶报告基因实验证实 GMDS-AS1 与 PSMB1 的结合。采用 Ki67 和 Edu 检测肿瘤细胞的增殖能力。采用 ChIP 实验验证 H3K9me1 与 lncRNA GMDS-AS1 启动子的关系。采用 Transwell 实验检测肿瘤细胞的迁移和侵袭能力。采用 CCK-8 实验检测肿瘤细胞的活力。采用流式细胞术检测肿瘤细胞的细胞周期。
GMDS-AS1 在 HCC 中的表达降低，ESET 的表达升高。GMDS-AS1 抑制促进肿瘤的发生，这种作用与 ESET 对 GMDS-AS1 的表观遗传抑制密切相关。PSMB1 是 GMDS-AS1 的下游靶基因，促进肿瘤增殖，受 GMDS-AS1 负调控。
我们的研究结果表明 lncRNA GMDS-AS1 在 HCC 中具有抗肿瘤特性，并解释了其受 ESET 介导的调控模式。我们的工作揭示了 GMDS-AS1 在 HCC 进展中的重要作用，并检测到 ESET 促进 HCC 的新途径。
