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长链非编码RNA NPBWR1-2通过多种微小RNA影响卵巢癌的发展。

Long non-coding RNA NPBWR1-2 affects the development of ovarian cancer via multiple microRNAs.

作者信息

Liu Shasha, Du Qiuyue, Rao Yang, Liu Caiyan, Qu Pengpeng

机构信息

Emergency Department, Tianjin Central Hospital of Gynecology Obstetrics, Tianjin 300100, P.R. China.

Pathology Department, Tianjin Central Hospital of Gynecology Obstetrics, Tianjin 300100, P.R. China.

出版信息

Oncol Lett. 2020 Jul;20(1):685-692. doi: 10.3892/ol.2020.11639. Epub 2020 May 18.

Abstract

Ovarian cancer has a high incidence rate and mortality in gynaecologic malignancies. Epithelial ovarian cancer (EOC) accounts for >95% of ovarian cancer cases. Most of the patients with EOC are difficult to diagnose in early stage. The aim of the present study was to compare the long non-coding (lnc)RNA expression profiles of five ovarian cancer cell lines (IGROV1, A2780, SKOV3, ES2, and Hey) and an ovarian epithelial cell line (IOSE80) in order to identify differentially expressed lncRNAs and their associated microRNAs (miRNAs). The expression profiles of lncRNAs and mRNAs in these cell lines were determined by microarray gene analysis and reverse transcription-quantitative PCR. lncRNA neuropeptides B and W receptor 1-2 (NPBWR1-2) overexpression was induced in the SKOV3 cell line. Cell viability, proliferation, migration, invasion and apoptosis were evaluated using MTT, colony-formation, Transwell and flow cytometry assays, respectively. The microarray results indicated that several lncRNAs were differentially expressed in the five ovarian cancer cell lines compared with the normal ovarian epithelial cell line. Compared with IOSE80, lncRNA NPBWR1-2 was downregulated by more than two-fold in all five ovarian cancer cell lines. Moreover, NPBWR1-2 overexpression in the SKOV3 cell line decreased cell viability, inhibited proliferation, migration and invasion, and promoted apoptosis compared with the control cells. A total of 20 miRNAs, which are involved in tumorigenesis and development, were predicted to be associated with NPBWR1-2 by bioinformatics analysis. The results of the present study suggest that lncRNA NPBWR1-2 affects the occurrence and development of ovarian cancer via multiple miRNAs, providing a theoretical basis for the development of novel clinical treatments.

摘要

卵巢癌在妇科恶性肿瘤中发病率和死亡率较高。上皮性卵巢癌(EOC)占卵巢癌病例的95%以上。大多数EOC患者在早期难以诊断。本研究的目的是比较五种卵巢癌细胞系(IGROV1、A2780、SKOV3、ES2和Hey)和一种卵巢上皮细胞系(IOSE80)的长链非编码(lnc)RNA表达谱,以鉴定差异表达的lncRNAs及其相关的微小RNA(miRNAs)。通过微阵列基因分析和逆转录定量PCR确定这些细胞系中lncRNAs和mRNAs的表达谱。在SKOV3细胞系中诱导lncRNA神经肽B和W受体1-2(NPBWR1-2)过表达。分别使用MTT、集落形成、Transwell和流式细胞术检测评估细胞活力、增殖、迁移、侵袭和凋亡。微阵列结果表明,与正常卵巢上皮细胞系相比,五种卵巢癌细胞系中有几种lncRNAs差异表达。与IOSE80相比,lncRNA NPBWR1-2在所有五种卵巢癌细胞系中下调超过两倍。此外,与对照细胞相比,SKOV3细胞系中NPBWR1-2过表达降低了细胞活力,抑制了增殖、迁移和侵袭,并促进了凋亡。通过生物信息学分析预测,共有20种参与肿瘤发生和发展的miRNAs与NPBWR1-2相关。本研究结果表明,lncRNA NPBWR1-2通过多种miRNAs影响卵巢癌的发生和发展,为新型临床治疗的开发提供了理论依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a22/7285903/07ae73ef75d5/ol-20-01-0685-g00.jpg

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