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微小RNA-133a在上皮性卵巢癌发病机制及进展中的作用

Role of microRNA-133a in epithelial ovarian cancer pathogenesis and progression.

作者信息

Luo Jie, Zhou Jianhong, Cheng Qi, Zhou Caiyun, Ding Zhiming

机构信息

Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310006, P.R. China.

出版信息

Oncol Lett. 2014 Apr;7(4):1043-1048. doi: 10.3892/ol.2014.1841. Epub 2014 Jan 29.

Abstract

It has been demonstrated that microRNA (miR)-133a is downregulated in a number of human malignancies and is closely associated with the progression of tumors. The present study was conducted to investigate the contribution of miR-133a to the initiation and malignant progression of human epithelial ovarian cancer (EOC). Quantitative polymerase chain reaction was employed to detect the expression of miR-133a in the human EOC OVCAR-3 cell line, normal human ovarian surface epithelial (tsT) cells and 96 tissue samples, including 70 EOC tissues and 26 normal ovarian tissue sections. Additionally, analysis of the correlation between miR-133a levels and clinicopathological characteristics was carried out. The effect of miR-133a on cell viability, apoptosis, invasion and migration was investigated following transfection with miR-133a mimics and negative control small interfering RNA in OVCAR-3 cells. Marked downregulation of miR-133a was observed in the OVCAR-3 cell line and primary tumor samples, and it was found that reduced miR-133a expression significantly correlated with advanced clinical stages, poor histological differentiation and lymph node metastasis. Furthermore, OVCAR-3 cell viability, invasion and migration were significantly inhibited, while cell apoptosis was increased, following transfection of miR-133a mimics. The present study reveals the critical role that miR-133a plays in EOC pathogenesis and development, indicating that it may act as a promising biomarker for predicting EOC progression and as a potential target for gene therapy.

摘要

已有研究表明,微小RNA(miR)-133a在多种人类恶性肿瘤中表达下调,且与肿瘤进展密切相关。本研究旨在探讨miR-133a对人类上皮性卵巢癌(EOC)起始和恶性进展的作用。采用定量聚合酶链反应检测miR-133a在人类EOC OVCAR-3细胞系、正常人卵巢表面上皮(tsT)细胞及96份组织样本(包括70份EOC组织和26份正常卵巢组织切片)中的表达。此外,还分析了miR-133a水平与临床病理特征之间的相关性。用miR-133a模拟物和阴性对照小干扰RNA转染OVCAR-3细胞后,研究了miR-133a对细胞活力、凋亡、侵袭和迁移的影响。在OVCAR-3细胞系和原发性肿瘤样本中观察到miR-133a明显下调,且发现miR-133a表达降低与临床晚期、组织学分化差和淋巴结转移显著相关。此外,转染miR-133a模拟物后,OVCAR-3细胞的活力、侵袭和迁移受到显著抑制,而细胞凋亡增加。本研究揭示了miR-133a在EOC发病机制和发展中的关键作用,表明它可能作为预测EOC进展的有前景的生物标志物以及基因治疗的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81be/3961467/a7cff6333fa7/OL-07-04-1043-g00.jpg

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