Author:
Sun Guogui,Ding Xiao,Bi Nan,Wu Lihong,Wang Jingbo,Zhang WenJue,Dong Xin,Lv Ning,Song Yongmei,Zhan Qimin,Wang LuHua
Abstract
AbstractDuring the last several years, a growing number of studies have shown that microRNAs (miRNAs) participate in cancer metastasis. Brain metastasis (BM) is a frequent complication of lung adenocarcinoma (LAD), and the incidence of locally advanced LAD with BM can be as high as 30–50%. This study was performed to identify the miRNA expression patterns of LAD with BM and to determine the biological role that miRNAs play in tumorigenesis. To this end, we conducted microarray and quantitative PCR analyses to evaluate BM-related miRNAs independently validated from a total of 155 patients with LAD. A series of in vivo and in vitro assays were also conducted to verify the impact of miRNAs on BM. We found significantly increased expression of miR-423-5p, and BM was predicted in non-small cell lung cancer when compared to LAD without BM. We next examined the function of miR-423-5p and discovered that it significantly promoted colony formation, cell motility, migration, and invasion in vitro. We computationally and experimentally confirmed that metastasis suppressor 1 (MTSS1) was a direct miR-423-5p target. Through a combination of image, histological, and molecular analyses, we found that miR-423-5p overexpression significantly increased tumor burden, local invasion, and distant BM. The level of MTSS1 expression was inversely correlated with miR-423-5p upregulation in the LAD specimens and was associated with survival of patients with BM. MiR-423-5p promoted BM in LAD and inhibited MTSS1 expression. Together, these results show that MiR-423-5p has the potential to be a marker of BM and/or a therapeutic target in LAD.
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Cell Biology,Cellular and Molecular Neuroscience,Immunology
Reference57 articles.
1. Jemal, A. et al. Global cancer statistics. CA 61, 69–90 (2011).
2. Anglim, P. P., Alonzo, T. A. & Laird-Offringa, I. A. DNA-methylation-based biomarkers for early detection of non-small cell lung cancer: an update. Mol. Cancer 7, 81 (2008).
3. Ding, X. et al. Risk factors of brain metastases in completely resected pathological stage IIIA-N2 non-small cell lung cancer. Radiat. Oncol. 7, 119 (2012).
4. Schoutten, L. J., Rutten, J., Huveneers, H. A. & Twijnstra, A. Incidence of brain metastasis in a cohort of patients with carcinoma of breast, colon, kidney, and lung and melanoma. Cancer 94, 2698–2705 (2002).
5. Mujoomdar, A. et al. Clinical predictors of metastatic disease to the brain from non-small cell lung carcinoma: primary tumor size, cell type, and lymph node metastases. Radiology 242, 882–888 (2007).
Cited by
31 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献