TUG1靶向增强抗癌免疫,从而促进lenvatinib在肝细胞癌中的疗效。

IF 4.5 3区 医学 Q1 GENETICS & HEREDITY
Siyao Che, Longguang He, Qinshou Chen, Yiqiao Mo, Fuliang Li, Junwei Huang, Zikang Ruan
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引用次数: 0

摘要

肝细胞癌(HCC)是全球癌症死亡的主要原因,预后较差。长链非编码RNA TUG1与此有关,但其在HCC中的具体作用尚不清楚。采用RT-qPCR评估TUG1和PD-L1的表达,采用GEO和TCGA数据库比较HCC患者和健康对照组的TUG1水平。体外,包括CCK8、菌落形成和transwell,评估细胞生长。通过HCC细胞共培养实验评估CD8 + T细胞的细胞毒性,并通过双荧光素酶报告基因检测检测miR-377-3p与TUG1和PD-L1的相互作用。结果表明,TUG1在HCC中表达上调,尤其是在晚期HCC中,PD-L1表达与TUG1水平呈正相关。值得注意的是,lenvatinib (LEN)治疗下调HCC细胞中的TUG1和PD-L1,增强CD8 + T细胞介导的细胞毒性。过表达TUG1会降低LEN的作用,而敲低TUG1会增强LEN的作用。机制上,TUG1海绵miR-377-3p,从而增加PD-L1的表达。在体内,TUG1敲除联合LEN治疗可显著降低肿瘤生长和PD-L1表达。总之,TUG1通过miR-377-3p增强PD-L1促进HCC进展,其敲低增强LEN的治疗效果,突出了TUG1作为HCC治疗新靶点的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
TUG1 targeting enhances anticancer immunity thereby facilitating lenvatinib efficacy in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a major cause of cancer death globally, with a poor prognosis. The long non-coding RNA TUG1 has been implicated, but its specific role in HCC remains unclear. RT-qPCR was used to evaluate TUG1 and PD-L1 expression, while GEO and TCGA databases were utilized to compare TUG1 levels between HCC patients and healthy controls. In vitro, including CCK8, colony formation, and transwell, assessed cell growth. CD8 + T cell cytotoxicity was evaluated through HCC cells co-culture experiments, and the interaction of miR-377-3p with TUG1 and PD-L1 was examined using dual-luciferase reporter assays. Results indicated that TUG1 was upregulated in HCC, particularly in advanced-stage disease, and PD-L1 expression positively correlated with TUG1 levels. Notably, lenvatinib (LEN) treatment downregulated both TUG1 and PD-L1 in HCC cells, enhancing CD8 + T cell-mediated cytotoxicity. Overexpression of TUG1 diminished the efficacy of LEN, while TUG1 knockdown enhanced it. Mechanistically, TUG1 was found to sponge miR-377-3p, thereby increasing PD-L1 expression. In vivo, TUG1 knockdown combined with LEN treatment significantly reduced tumor growth and PD-L1 expression. In conclusion, TUG1 promotes HCC progression by enhancing PD-L1 through miR-377-3p, with its knockdown enhancing the therapeutic efficacy of LEN, highlighting TUG1's potential as a novel target for HCC treatment.

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来源期刊
Genes and immunity
Genes and immunity 医学-免疫学
CiteScore
8.90
自引率
4.00%
发文量
28
审稿时长
6-12 weeks
期刊介绍: Genes & Immunity emphasizes studies investigating how genetic, genomic and functional variations affect immune cells and the immune system, and associated processes in the regulation of health and disease. It further highlights articles on the transcriptional and posttranslational control of gene products involved in signaling pathways regulating immune cells, and protective and destructive immune responses.
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