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miR-1323通过靶向Cbl-b促进肺腺癌细胞迁移,是一种早期预后生物标志物。

miR-1323 Promotes Cell Migration in Lung Adenocarcinoma by Targeting Cbl-b and Is an Early Prognostic Biomarker.

作者信息

Zhao Huan, Zheng Chunlei, Wang Yizhe, Hou Kezuo, Yang Xianghong, Cheng Yang, Che Xiaofang, Xie Shilin, Wang Shuo, Zhang Tieqiong, Kang Jian, Liu Yunpeng, Pan Dianzhu, Qu Xiujuan, Hu Xuejun, Fan Yibo

机构信息

Department of Respiratory and Infectious Disease of Geriatrics, The First Hospital of China Medical University, Shenyang, China.

Department of Respiratory, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.

出版信息

Front Oncol. 2020 Feb 21;10:181. doi: 10.3389/fonc.2020.00181. eCollection 2020.

Abstract

MicroRNAs are known to regulate cellular processes in non-small cell lung cancer (NSCLC) cells and predict prognosis. However, identification of specific microRNAs in NSCLC as potential therapeutic targets is controversial. We aim to determine the clinical significance of miR-1323 in the prognosis of patients with lung cancer and the potential mechanism. A bioinformatics approach was used to screen the importance microRNA in NSCLC through the online GEO database (GSE42425). The relationship between expression level of miR-1323 and overall survival of lung cancer patients was analyzed. Additionally, an independent corhort including 53 NSCLC cases that underwent resection validated the connection between miR-1323 and LUAD patients' overall survival. Next, the function of miR-1323 was studied by transient transfection. A more in-depth mechanism was studied through luciferase reporter gene experiments. High miR-1323 expression correlated with poor survival in NSCLC patients ( = 0.011), and in lung adenocarcinoma (LUAD) patients ( = 0.015) based on GEO database (GSE42425). In the independent cohort based on our hospital, high miR-1323 expression was associated with LUAD patients ( = 0.025). Moreover, transfection with mimics of miR-1323 showed an increased migratory capacity in LUAD A549 and HCC827 cells. In addition, E3 ubiquitin-protein ligase Casitas B-lineage Lymphoma-b (Cbl-b) was found to be the target genes of miR-1323 and significantly down regulated after mimics of miR-1323 transfection, and high Cbl-b expression predicted better prognosis in NSCLC and LUAD ( = 0.00072 and = 0.02, respectively). The miR-1323 promoted LUAD migration through inhibiting Cbl-b expression. High miR-1323 expression predicted poor prognosis in LUAD patients.

摘要

已知微小RNA可调节非小细胞肺癌(NSCLC)细胞中的细胞过程并预测预后。然而,将NSCLC中的特定微小RNA鉴定为潜在治疗靶点存在争议。我们旨在确定miR-1323在肺癌患者预后中的临床意义及潜在机制。采用生物信息学方法通过在线GEO数据库(GSE42425)筛选NSCLC中重要的微小RNA。分析了miR-1323表达水平与肺癌患者总生存期的关系。此外,一个包含53例接受切除术的NSCLC病例的独立队列验证了miR-1323与肺腺癌(LUAD)患者总生存期之间的联系。接下来,通过瞬时转染研究miR-1323的功能。通过荧光素酶报告基因实验研究了更深入的机制。基于GEO数据库(GSE42425),miR-1323高表达与NSCLC患者(P = 0.011)及肺腺癌(LUAD)患者(P = 0.015)的不良生存相关。在基于我们医院的独立队列中,miR-1323高表达与LUAD患者相关(P = 0.025)。此外,用miR-1323模拟物转染显示LUAD A549和HCC827细胞的迁移能力增强。另外,发现E3泛素蛋白连接酶Casitas B系淋巴瘤b(Cbl-b)是miR-1323的靶基因,在miR-1323模拟物转染后显著下调,且Cbl-b高表达预测NSCLC和LUAD的预后较好(分别为P = 0.00072和P = 0.02)。miR-1323通过抑制Cbl-b表达促进LUAD迁移。miR-1323高表达预测LUAD患者预后不良。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8da1/7047338/1c5005feb070/fonc-10-00181-g0001.jpg

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