miR-550a-5p Functions as a Tumor Promoter by Targeting LIMD1 in Lung Adenocarcinoma.
miR-550a-5p Functions as a Tumor Promoter by Targeting LIMD1 in Lung Adenocarcinoma.
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miR-550a-5p 通过靶向肺腺癌中的 LIMD1 作为肿瘤启动子
DOI：
10.3389/fonc.2020.570733
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发表时间：
2020
影响因子：
4.7
通讯作者：
Chen YJ
中科院分区：
文献类型：
--
作者：
Guo ZZ;Ma ZJ;He YZ;Jiang W;Xia Y;Pan CF;Wei K;Shi YJ;Chen L;Chen YJ
在大多数国家，肺腺癌占所有肺癌病例的一半。越来越多的证据表明microRNA在癌症进展中起着重要作用，其中一些可以被鉴定为潜在的生物标志物。本研究旨在探讨miR-550a-5p在肺癌中的作用。miR-550a-5p是通过R-studio和Perl从TCGA数据库中筛选出的一种成熟的肺腺癌相关microRNA，在样本中表达丰富，且存在5年生存预后差异，尚未在肺癌中进行研究。通过在线数据库预测潜在的靶基因。利用FunRich、STRING数据库和Cytoscape构建基因本体富集、途径富集、蛋白质-蛋白质相互作用网络和枢纽基因-microRNA网络。然后，发现多篇文章报道的已知肿瘤抑制基因LIMD1与miR-550a-5p呈负相关。miR-550a-5p在肿瘤样品和肿瘤相关细胞系中表达上调。其高表达与肿瘤大小有关。miR-550a-5p过表达的A549细胞株促进肿瘤增殖，而miR-550a-5p敲低的H1299细胞株则表现出相反的结果。双荧光素酶检测证实miR-550a-5p通过直接与LIMD1的3 ′-UTR结合负调控LIMD1。总之，通过生物信息学分析和体外和体内实验验证，已经确定了一种新的潜在预后和治疗生物标志物miR-550a-5p，其通过沉默已知的抑癌基因LIMD1促进肺腺癌。
Lung adenocarcinoma accounts for half of all lung cancer cases in most countries. Mounting evidence has demonstrated that microRNAs play important roles in cancer progression, and some of them can be identified as potential biomarkers. This study aimed to explore the role of miR-550a-5p, a lung adenocarcinoma-associated mature microRNA screened out from the TCGA database via R-studio and Perl, with abundant expression in samples and with 5-year survival prognosis difference, as well as having not been studied in lung cancer yet. Potential target genes were predicted by the online database. Gene ontology enrichment, pathway enrichment, protein–protein interaction network, and hub genes–microRNA network were constructed by FunRich, STRING database, and Cytoscape. Then, LIMD1, a known tumor suppressor gene reported by multiple articles, was found to have a negative correlation with miR-550a-5p. The expression of miR-550a-5p was up-regulated in tumor samples and tumor-associated cell lines. Its high expression was also correlated with tumor size. Cell line A549 treated with miR-550a-5p overexpression promoted tumor proliferation, while H1299 treated with miR-550a-5p knockdown showed the opposite result. Mechanically, miR-550a-5p negatively regulated LIMD1 by directly binding to its 3′-UTR validated by dual luciferase assay. In summary, a new potential prognostic and therapeutic biomarker, miR-550a-5p, has been identified by bioinformatics analysis and experimental validation in vitro and in vivo, which promotes lung adenocarcinoma by silencing a known suppressor oncogene LIMD1.
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DOI：
10.1016/j.cub.2010.02.035
发表时间：
2010-04-13
期刊：
Current biology : CB
影响因子：
--
作者：
Das Thakur M;Feng Y;Jagannathan R;Seppa MJ;Skeath JB;Longmore GD
通讯作者：
Longmore GD
影响因子：
64.5
作者：
Hafner M;Landthaler M;Burger L;Khorshid M;Hausser J;Berninger P;Rothballer A;Ascano M Jr;Jungkamp AC;Munschauer M;Ulrich A;Wardle GS;Dewell S;Zavolan M;Tuschl T
通讯作者：
Tuschl T
影响因子：
4.1
作者：
Chakraborty, Chandraditya;Mitra, Sraboni;Panda, Chinmay Kumar
通讯作者：
Panda, Chinmay Kumar
DOI：
10.1073/pnas.0805003105
发表时间：
2008-12-16
影响因子：
11.1
作者：
Sharp, Tyson V.;Al-Attar, Ahmad;Longmore, Gregory D.
通讯作者：
Longmore, Gregory D.
有丝分裂中的 LIMD1 磷酸化是有丝分裂进展及其肿瘤抑制活性所必需的
影响因子：
5.4
作者：
Zhou, Jiuli;Zhang, Lin;Dong, Jixin
通讯作者：
Dong, Jixin