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microRNA-510 在非小细胞肺癌中通过直接靶向 SRC 激酶信号抑制剂 1 发挥致癌作用。

MicroRNA-510 Plays Oncogenic Roles in Non-Small Cell Lung Cancer by Directly Targeting SRC Kinase Signaling Inhibitor 1.

机构信息

Department of Pathology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, P.R. China.

Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, The First Affiliated Hospital of Soochow University, Suzhou, P.R. China.

出版信息

Oncol Res. 2019 Aug 8;27(8):879-887. doi: 10.3727/096504018X15451308507747. Epub 2019 Apr 14.

Abstract

An increasing number of studies have demonstrated that microRNAs (miRNAs) may play key roles in various cancer carcinogenesis and progression, including non-small cell lung cancer (NSCLC). However, the expressions, roles, and mechanisms of miR-510 in NSCLC have, up to now, been largely undefined. In vivo assay showed that miR-510 was upregulated in NSCLC tissues compared with that in adjacent nontumor lung tissues. miR-510 expression was significantly correlated with TNM stage and lymph node metastasis. In vitro assay indicated that expressions of miR-510 were also increased in NSCLC cell lines. Downregulation of miR-510 suppressed NSCLC cell proliferation and invasion in vitro. We identified SRC kinase signaling inhibitor 1 (SRCIN1) as a direct target gene of miR-510 in NSCLC. Expression of SRCIN1 was downregulated in lung cancer cells and negatively correlated with miR-510 expression in tumor tissues. Downregulation of SRCIN1, leading to inhibition of miR-510 expression, reversed cell proliferation and invasion in NSCLC cells. These results showed that miR-510 acted as an oncogenic miRNA in NSCLC, partly by targeting SRCIN1, suggesting that miR-510 can be a potential approach for the treatment of patients with malignant lung cancer.

摘要

越来越多的研究表明,微小 RNA(miRNA)可能在包括非小细胞肺癌(NSCLC)在内的各种癌症的发生和发展中发挥关键作用。然而,miR-510 在 NSCLC 中的表达、作用和机制至今仍未完全阐明。体内实验表明,miR-510 在 NSCLC 组织中的表达高于相邻非肿瘤肺组织。miR-510 的表达与 TNM 分期和淋巴结转移显著相关。体外实验表明,miR-510 在 NSCLC 细胞系中的表达也增加了。miR-510 的下调抑制了 NSCLC 细胞的体外增殖和侵袭。我们鉴定 SRC 激酶信号抑制剂 1(SRCIN1)为 NSCLC 中 miR-510 的直接靶基因。SRCIN1 在肺癌细胞中的表达下调,并与肿瘤组织中的 miR-510 表达呈负相关。SRCIN1 的下调,导致 miR-510 表达的抑制,逆转了 NSCLC 细胞的增殖和侵袭。这些结果表明,miR-510 在 NSCLC 中作为一种致癌 miRNA 发挥作用,部分通过靶向 SRCIN1,表明 miR-510 可作为治疗恶性肺癌患者的潜在方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e02/7848405/80eaf64a8e8b/OR-27-879-g001.jpg

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