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MiR-140-3p通过下调非小细胞肺癌中ATP8A1的表达来抑制细胞生长和侵袭。

MiR-140-3p suppressed cell growth and invasion by downregulating the expression of ATP8A1 in non-small cell lung cancer.

作者信息

Dong Wei, Yao Chunping, Teng Xuepeng, Chai Jie, Yang Xinhua, Li Baosheng

机构信息

Shandong University School of Medicine, 44# Wenhua Xi Road, Jinan, 250012, Shandong, People's Republic of China.

Department of Radiation Oncology, Shandong Cancer Hospital and Institute, 440# Jiyan Road, Jinan, 250117, Shandong, People's Republic of China.

出版信息

Tumour Biol. 2016 Mar;37(3):2973-85. doi: 10.1007/s13277-015-3452-9. Epub 2015 Sep 28.

Abstract

MicroRNAs (miRNAs) as a class of small noncoding RNA molecules regulate the expression of targeted gene. The dysregulation of microRNAs is reported to be involved in carcinogenesis and tumor progression. Here, we identified miR-140-3p as a downregulated microRNA in most cancer tissues including lung cancer tissues, compared with their normal counterparts. MiR-140-3p was observed to perform its tumor suppressor function via its inhibition on cell growth, migration and invasion but its induction of cell apoptosis. Furthermore, the growth of non-small-cell lung cancer (NSCLC) cells in nude mouse models were suppressed by overexpression of miR-140-3p. ATP8A1 was demonstrated as a novel direct target of miR-140-3p using a luciferase assay. The increased level of intracellular ATP8A1 protein attenuated the inhibitor role of miR-140-3p in the growth and mobility of NSCLC cell. A regulation mechanism of miR-140-3p for the development and progression of NSCLC through downregulating the ATP8A1 expression was first discovered in the present study.

摘要

微小RNA(miRNA)作为一类小的非编码RNA分子,可调控靶基因的表达。据报道,微小RNA的失调与癌症发生和肿瘤进展有关。在此,我们发现与正常组织相比,miR-140-3p在包括肺癌组织在内的大多数癌症组织中是下调的微小RNA。观察到miR-140-3p通过抑制细胞生长、迁移和侵袭以及诱导细胞凋亡来发挥其肿瘤抑制功能。此外,在裸鼠模型中,miR-140-3p的过表达抑制了非小细胞肺癌(NSCLC)细胞的生长。使用荧光素酶测定法证明ATP8A1是miR-140-3p的一个新的直接靶点。细胞内ATP8A1蛋白水平的升高减弱了miR-140-3p对NSCLC细胞生长和迁移的抑制作用。本研究首次发现了miR-140-3p通过下调ATP8A1表达对NSCLC发生发展的调控机制。

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