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Ketamine Inhibits Ovarian Cancer Cell Growth by Regulating the lncRNA-PVT1/EZH2/p57 Axis.

ABSTRACT: Ketamine is widely used for cancer pain treatment in clinic, and has been shown to inhibit various tumor cells growth. However, the effect of ketamine on ovarian cancer cells growth and the downstream molecules has not been defined. In the present study, we found that ketamine significantly inhibited the proliferation and survival of six ovarian cancer cell lines. Moreover, ketamine induced ovarian cancer cell cycle arrest, apoptosis, and inhibited colony formation capacity. Since lncRNAs have been identified as key regulators of cancer development, we performed bioinformatics analysis of a GEO dataset and found fourteen significantly altered lncRNAs in ovarian cancer patients. We then investigated the effect of ketamine on these lncRNAs, and found that ketamine regulated the expression of lncRNA PVT1. Mechanistically, ketamine regulated P300-mediated H3K27 acetylation activation in the promoter of PVT1. Our RNA immunoprecipitation experiment indicated that PVT1 bound histone methyltransferase enhancer of zeste homolog 2 (EZH2), and regulated the expression of target gene, including p57, and consequently altered ovarian cancer cell biology. Our study revealed that ketamine could be a potential therapeutic strategy for ovarian cancer patients.

SUBMITTER: Li T

PROVIDER: S-EPMC7982774 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Ketamine Inhibits Ovarian Cancer Cell Growth by Regulating the lncRNA-PVT1/EZH2/p57 Axis.

Li Tao T Yang Jie J Yang Ben B Zhao Guoqing G Lin Hai H Liu Qi Q Wang Leiming L Wan Yingchun Y Jiang Hongyang H

Frontiers in genetics 20210308

Ketamine is widely used for cancer pain treatment in clinic, and has been shown to inhibit various tumor cells growth. However, the effect of ketamine on ovarian cancer cells growth and the downstream molecules has not been defined. In the present study, we found that ketamine significantly inhibited the proliferation and survival of six ovarian cancer cell lines. Moreover, ketamine induced ovarian cancer cell cycle arrest, apoptosis, and inhibited colony formation capacity. Since lncRNAs have b ...[more]

PMID: 33763107

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Project description:ObjectiveOur study aims to evaluate the role of long non-coding RNA variant translocation gene Pvt1 in cardiomyocyte apoptosis, as well as the potential targets and mechanisms involved in Pvt1-miRNA-mRNA axis.Methods1.Pvt1 knockdown in cells by transfection with small interfering RNA (si-Pvt1), HL-1 cells were randomly divided into control group, hypoxia group, hypoxia + negative control group and hypoxia + si-Pvt1 group. Apoptosis-related genes expression was detected by Western blot assay, RT-qPCR and Flow cytometry assay. 2.Pvt1 knockdown model (sh-Pvt1) was established by injecting adeno-associated virus (AAV) vector shRNA-Pvt1 into the caudal vein 7 days before myocardial infarction, and echocardiography was used to measure cardiac function 7 days after myocardial infarction induced by ligation of the left anterior descending branch. HE staining was used to evaluate the pathological injury of mouse heart tissue, and the apoptotic protein expression was detected by Western blot. 3.lncRNA-related microRNAs were predicted by bioinformatics tools and further verified by dual luciferase experiment. Western blot analysis was used to identify the expression of apoptotic genes following the simultaneous transfection of si-Pvt1 and miR-216 mimics. Genes differentially expressed in hypoxia + si-NC and hypoxia + si-Pvt1 groups were identified by RNA sequencing. These genes were then compared with the target genes of miR-216 predicted by bioinformatics tools. The gene of interest Ccnd3 was excluded from the analysis. Western blot analysis was used to assess the expression of Apoptosis-related proteins in HL-1 cells co-transfected with miR-216 mimics and overexpressed Ccnd3.Results1. Pvt1 was highly expressed in HL-1 induced by hypoxia, and Pvt1 knockdown can reduce cell apoptosis in hypoxia cells. 2. MI causes myocardial injury in mice, and inhibition of Pvt 11 can improve the cardiac function of mice with myocardial infarction, prevent some inflammatory cell infiltration, and reduce myocardial cell apoptosis. 3. Pvt1 acts as a sponge for miR-216 and promotes the expression of Ccnd3.ConclusionPvt1 may promote myocardial infarct-induced apoptosis through the miR-216/Ccnd3 axis.

Dataset Information

Ketamine Inhibits Ovarian Cancer Cell Growth by Regulating the lncRNA-PVT1/EZH2/p57 Axis.

Publications

Ketamine Inhibits Ovarian Cancer Cell Growth by Regulating the lncRNA-PVT1/EZH2/p57 Axis.

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