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KRAS-G12D 突变和 P53 敲除的小鼠肺腺癌中失调的长非编码 RNA 表达谱。

Deregulated lncRNA expression profile in the mouse lung adenocarcinomas with KRAS-G12D mutation and P53 knockout.

机构信息

Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, & Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.

Zhongshan Hospital, Fudan University, Shanghai, China.

出版信息

J Cell Mol Med. 2019 Oct;23(10):6978-6988. doi: 10.1111/jcmm.14584. Epub 2019 Aug 14.

Abstract

Recent studies have demonstrated that aberrant long non-coding RNAs (lncRNAs) expression are suggested to be closely associated with multiple human diseases, lung cancer included. However, the roles of lncRNAs in lung cancer are not well understood. In this study, we used microarrays to investigate the aberrantly expressed lncRNAs in the mouse lung adenocarcinoma with P53 knockout and the Kras mutation. Results revealed that 6424 lncRNAs were differentially expressed (≥ 2-fold change, P < .05). Two hundred and ten lncRNAs showed more than 8-fold change and conserved across human and were further analysed in the primary mouse lung adenocarcinoma KP cells, which were isolated from the p53 knockout and the Kras mutation mice. Among all the 210 lncRNAs, 11 lncRNAs' expression was regulated by P53, 33 lncRNAs by KRAS and 13 lncRNAs by hypoxia in the primary KP cells, respectively. NONMMUT015812, which was remarkably up-regulated in the mouse lung adenocarcinoma and negatively regulated by the P53 re-expression, was detected to analyse its cellular function. Results showed that knockdown of NONMMUT015812 by shRNAs decreased proliferation and migration abilities of KP cells. Among those aberrantly expressed lncRNAs in the mouse lung adenocarcinoma, NONMMUT015812 was a potential oncogene.

摘要

最近的研究表明,异常长的非编码 RNA(lncRNA)的表达与多种人类疾病密切相关,包括肺癌。然而,lncRNA 在肺癌中的作用还不是很清楚。在这项研究中,我们使用微阵列技术研究了具有 P53 缺失和 Kras 突变的小鼠肺腺癌中异常表达的 lncRNA。结果显示,有 6424 个 lncRNA 表达差异(≥ 2 倍变化,P <.05)。有 210 个 lncRNA 的变化倍数超过 8 倍,且在人类中保守,在从 p53 缺失和 Kras 突变的小鼠中分离出来的原代小鼠肺腺癌 KP 细胞中进一步进行分析。在所有 210 个 lncRNA 中,有 11 个 lncRNA 的表达受 P53 调控,33 个受 KRAS 调控,13 个受缺氧调控,分别在原代 KP 细胞中。NONMMUT015812 在小鼠肺腺癌中显著上调,并且其表达受 P53 再表达的负调控,我们对其进行了细胞功能分析。结果表明,shRNA 下调 NONMMUT015812 降低了 KP 细胞的增殖和迁移能力。在这些在小鼠肺腺癌中异常表达的 lncRNA 中,NONMMUT015812 是一个潜在的癌基因。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca96/6787463/00741bd55733/JCMM-23-6978-g001.jpg

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