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miR-200c 的下调促进乳酸脱氢酶 A 的表达和非小细胞肺癌的进展。

The Downregulation of miR-200c Promotes Lactate Dehydrogenase A Expression and Non-Small Cell Lung Cancer Progression.

机构信息

Department of Cardiothoracic Surgery, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, P.R. China.

出版信息

Oncol Res. 2018 Aug 23;26(7):1015-1022. doi: 10.3727/096504018X15151486241153. Epub 2018 Jan 10.

Abstract

This study was aimed to investigate the function and mechanism of microRNA-200c (miR-200c) in the progression of non-small cell lung cancer (NSCLC). A total of 76 patients diagnosed as having NSCLC were enrolled in this study. The expression level of miR-200c in NSCLC tissues and cell lines was investigated using the quantitative real-time polymerase chain reaction (RT-qPCR) method. We found that the expression of miR-200c was significantly reduced in NSCLC tissues and cell lines compared with normal lung tissues and the human bronchial epithelial cell line. Overexpression of miR-200c using the miR-200c mimic significantly suppressed cell proliferation and migration of NSCLC cell lines. The results of the luciferase reporter assay identified lactate dehydrogenase A (LDHA) as a direct target of miR-200c. The expression of LDHA was shown to be suppressed in NSCLC cell lines with miR-200c mimic transfection. Furthermore, the transfection of small interfering RNA (siRNA) targeting LDHA suppressed the proliferation and migration of NSCLC cell lines. In summary, our results presented in this study suggested that miR-200c was able to inhibit the proliferation and migration of NSCLC cells by downregulating LDHA. Therefore, miR-200c may be considered as a potential candidate for the treatment of NSCLC.

摘要

本研究旨在探讨 microRNA-200c(miR-200c)在非小细胞肺癌(NSCLC)进展中的功能和机制。本研究共纳入 76 例经诊断患有 NSCLC 的患者。采用实时定量聚合酶链反应(RT-qPCR)方法检测 NSCLC 组织和细胞系中 miR-200c 的表达水平。我们发现,与正常肺组织和人支气管上皮细胞系相比,NSCLC 组织和细胞系中 miR-200c 的表达明显降低。用 miR-200c 模拟物过表达 miR-200c 可显著抑制 NSCLC 细胞系的增殖和迁移。荧光素酶报告基因检测结果表明,乳酸脱氢酶 A(LDHA)是 miR-200c 的直接靶标。miR-200c 模拟物转染的 NSCLC 细胞系中 LDHA 的表达受到抑制。此外,转染针对 LDHA 的小干扰 RNA(siRNA)可抑制 NSCLC 细胞系的增殖和迁移。总之,本研究结果表明,miR-200c 通过下调 LDHA 抑制 NSCLC 细胞的增殖和迁移。因此,miR-200c 可能被视为治疗 NSCLC 的潜在候选药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b896/7844790/01d0424e4cc0/OR-26-1015-g001.jpg

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