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微小RNA-199a-5p通过靶向丝裂原活化蛋白激酶激酶激酶11抑制非小细胞肺癌。

MiR-199a-5p suppresses non-small cell lung cancer via targeting MAP3K11.

作者信息

Li Yanli, Wang Detao, Li Xue, Shao Yang, He Yanyun, Yu Huansha, Ma Zhongliang

机构信息

Lab for Noncoding RNA & Cancer, School of Life Sciences, Shanghai University, Shanghai 200444, China.

Exprimental Center for Life Sciences, School of Life Sciences, Shanghai University, Shanghai 200444, China.

出版信息

J Cancer. 2019 Jun 2;10(11):2472-2479. doi: 10.7150/jca.29426. eCollection 2019.

Abstract

MicroRNAs (miRNAs) comprise a class of short, non-coding RNAs that directly target 3'UTR of mRNA, causing subsequent degradation or suppression of translation. Here, we verified that miR-199a-5p was significantly down-regulated in mouse NSCLC tissues and human patient samples. To further study the function of miR-199a-5p, lentivirus system was adopted to construct stably over-expressing miR-199a-5p A549, SPC-A1 and H1299 cell lines. Then, miR-199a-5p played a tumor suppression role via directly targeting MAP3K11 gene in non-small cell lung cancer (NSCLC). Elevated miR-199a-5p suppressed cell proliferation and arrested cell cycle in G1 phase. We found that MAP3K11 was negatively correlated with miR-199a-5p in NSCLC patient tissues and mouse xenograft tumors. Our results suggest that miR-199a-5p together with its target gene MAP3K11 is a key factor and constitutes a complicated regulation network in NSCLC.

摘要

微小RNA(miRNA)是一类短链非编码RNA,可直接靶向mRNA的3'非翻译区(3'UTR),导致随后的mRNA降解或翻译抑制。在此,我们证实miR-199a-5p在小鼠非小细胞肺癌(NSCLC)组织和人类患者样本中显著下调。为进一步研究miR-199a-5p的功能,采用慢病毒系统构建稳定过表达miR-199a-5p的A549、SPC-A1和H1299细胞系。然后,miR-199a-5p通过直接靶向非小细胞肺癌(NSCLC)中的MAP3K11基因发挥肿瘤抑制作用。miR-199a-5p水平升高可抑制细胞增殖并使细胞周期停滞在G1期。我们发现,在NSCLC患者组织和小鼠异种移植瘤中,MAP3K11与miR-199a-5p呈负相关。我们的结果表明,miR-199a-5p及其靶基因MAP3K11是NSCLC中的关键因素,并构成了一个复杂的调控网络。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/caa9/6584351/808e72214d93/jcav10p2472g001.jpg

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