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EZH2 介导的长非编码 RNA ABHD11-AS1 启动子通过靶向 miR-133a-3p 调控卵巢癌细胞的进展。

EZH2-mediated lncRNA ABHD11-AS1 promoter regulates the progression of ovarian cancer by targeting miR-133a-3p.

机构信息

Departments of Obstetrics.

Urology, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, People's Republic of China.

出版信息

Anticancer Drugs. 2021 Mar 1;32(3):269-277. doi: 10.1097/CAD.0000000000001039.

Abstract

Long-chain noncoding RNAs (lncRNAs) are involved in a wide range of biological and pathological processes in ovarian cancer. The purpose of this study was to investigate the effects of EZH2-mediated ABHD11-AS1 promoter on the pathogenesis of ovarian cancer. The expression levels of EZH2, ABHD11-AS1 and miR-133a-3p were examined in ovarian cancer tissues using reverse transcription-quantitative PCR. Cell proliferation was evaluated using cell counting kit 8 assay, and cell invasion/migration was determined using a Transwell assay. Cell apoptosis was evaluated using flow cytometry. Dual luciferase assay was performed to confirm the interaction between ABHD11-AS1 and miR-133a-3p. The binding site of H3K27me3 on ABHD11-AS1 promoter was confirmed by ChIP. The expression of ABHD11-AS1 was significantly upregulated in ovarian cancer samples, and its levels were closely associated with lymph node metastasis, tumor stage and 3-year survival rate. Furthermore, interference of ABHD11-AS1 suppressed the proliferation, migration and invasion of ovarian cancer cells, while cell apoptosis was promoted. Additionally, miR-133a-3p could be a novel target of ABHD11-AS1, and EZH2-mediated H3K27me3 protein might bind to ABHD11-AS1 promoter directly. Moreover, rescue experiments indicated that the effects caused by ABHD11-AS1 knockdown on the malignant characteristics of ovarian cancer cells were notably enhanced by miR-133a-3p mimics, whereas the influences on cell growth and metastasis induced by overexpressed ABHD11-AS1 were abrogated by the restoration of miR-133a-3p expression. In summary, EZH2-mediated enrichment of H3K27me3 on ABHD11-AS1 promoter could regulate the progression of ovarian cancer via miR-133a-3p. Therefore, EZH2/ABHD11-AS1/miR-133a-3p axis might be a putative candidate for targeted treatment of ovarian cancer.

摘要

长链非编码 RNA(lncRNA)参与卵巢癌的广泛的生物学和病理学过程。本研究旨在探讨 EZH2 介导的 ABHD11-AS1 启动子对卵巢癌发病机制的影响。采用逆转录定量 PCR 检测卵巢癌组织中 EZH2、ABHD11-AS1 和 miR-133a-3p 的表达水平。通过细胞计数试剂盒 8 检测细胞增殖,通过 Transwell 检测细胞侵袭/迁移。通过流式细胞术检测细胞凋亡。通过双荧光素酶报告基因实验证实 ABHD11-AS1 和 miR-133a-3p 之间的相互作用。通过 ChIP 证实 ABHD11-AS1 启动子上 H3K27me3 的结合位点。ABHD11-AS1 在卵巢癌样本中表达显著上调,其水平与淋巴结转移、肿瘤分期和 3 年生存率密切相关。此外,ABHD11-AS1 的干扰抑制了卵巢癌细胞的增殖、迁移和侵袭,同时促进了细胞凋亡。此外,miR-133a-3p 可能是 ABHD11-AS1 的一个新靶点,EZH2 介导的 H3K27me3 蛋白可能直接与 ABHD11-AS1 启动子结合。此外,挽救实验表明,ABHD11-AS1 敲低对卵巢癌细胞恶性特征的影响通过 miR-133a-3p 模拟物显著增强,而通过恢复 miR-133a-3p 的表达则消除了过表达 ABHD11-AS1 对细胞生长和转移的影响。总之,EZH2 介导的 ABHD11-AS1 启动子上 H3K27me3 的富集可以通过 miR-133a-3p 调节卵巢癌的进展。因此,EZH2/ABHD11-AS1/miR-133a-3p 轴可能是卵巢癌靶向治疗的潜在候选物。

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