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长非编码 RNA GHET1 通过氧化应激促进前列腺癌细胞增殖。

Long noncoding RNA GHET1 promotes cell proliferation through oxidative stress in prostate cancer.

机构信息

Department of Pathology, Affiliated Dongguan Hospital, Southern Medical University, Dongguan, Guangdong, China.

出版信息

J Biochem Mol Toxicol. 2023 Jul;37(7):e23369. doi: 10.1002/jbt.23369. Epub 2023 Apr 7.

Abstract

Gastric carcinoma high expressed transcript 1 (GHET1) is an oncogenic Long noncoding RNA. GHET1 expression promotes multiple levels of developing a complex molecular network. The main purpose of the study was to investigate the mechanism by which long noncoding RNA (lncRNA) GHET1 promotes prostate cancer cell proliferation and related metabolism. In vitro study, lncRNA GHET1 was overexpressed in LN-cap, PC-3, 22RV1, and C4-2 cells. The cell viability was measured by MTT and trans-well assay. A flow cytometer was also used to detect cell cycles and apoptosis. Western blot analysis was used for protein expression validation. mRNA expression was detected by real-time PCR. lncRNA GHET1 enhanced cell proliferation, migration, and could resist paclitaxel-induced apoptosis and cell cycle arrest GHET1 expression stimulates reactive oxygen species (ROS) level upregulated in prostate cancer cells, increased the expression of HIFα, IL-1B and IL-6, and activated ROS/STAT-3/Twsit1 signaling pathway. Knockdown GHET1 could reduce cell proliferation and migration due to the overexpression of GHET1. lncRNA GHET1 promotes prostate cancer growth through oxidative stress signaling pathways and resists the antineoplastic drug paclitaxel, which can be used as a target for antineoplastic therapy and drug resistance therapy in the future in clinics.

摘要

胃腺癌高表达转录本 1(GHET1)是一种致癌的长非编码 RNA。GHET1 的表达促进了多层次的复杂分子网络的形成。本研究的主要目的是探讨长非编码 RNA(lncRNA)GHET1 促进前列腺癌细胞增殖及相关代谢的机制。在体外研究中,过表达 lncRNA GHET1 于 LN-cap、PC-3、22RV1 和 C4-2 细胞中。通过 MTT 和 Transwell 测定法测量细胞活力。还使用流式细胞仪检测细胞周期和凋亡。通过 Western blot 分析验证蛋白表达。通过实时 PCR 检测 mRNA 表达。lncRNA GHET1 增强细胞增殖、迁移,并且能够抵抗紫杉醇诱导的细胞凋亡和细胞周期阻滞。GHET1 表达刺激前列腺癌细胞中活性氧(ROS)水平上调,增加 HIFα、IL-1B 和 IL-6 的表达,并激活 ROS/STAT-3/Twsit1 信号通路。由于 GHET1 的过表达,敲低 GHET1 可减少细胞增殖和迁移。lncRNA GHET1 通过氧化应激信号通路促进前列腺癌的生长,并抵抗抗肿瘤药物紫杉醇,这在未来的临床实践中可作为抗肿瘤治疗和耐药治疗的靶点。

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