Down-regulation of miR-675-5p contributes to tumor progression and development by targeting pro-tumorigenic GPR55 in non-small cell lung cancer

Molecular Cancer

Research

Bin Shan¹  Xiyun Deng²  Yanwu Zhou³  Yang Gao³  Zhuchu Chen³  Chunfang Zhang³  Bin Li³  Wei Chen³  Dan He³  Jun Wang³  Jidong Hong³  Chaojun Duan³ 

[1] College of Medical Sciences, Washington State University Spokane, 412 E.Spokane Falls Boulevard, 99202, Spokane, WA, USA;Faculty of Basic Medical Sciences, College of Medicine, Hunan Normal University, 410013, Changsha, PR China;Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Institute of Medical Sciences, Xiangya Hospital, Central South University, Xiangya Road 87th, 410008, Changsha, Hunan, PR China;

关键词: miR-675-5p;    Progression;    NSCLC;    GPR55;   

DOI  :  10.1186/s12943-015-0342-0

 received in 2014-09-09, accepted in 2015-03-12,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundmicroRNAs are small noncoding RNAs that modulate a variety of cellular processes by regulating multiple targets, which can promote or inhibit the development of malignant behaviors. Accumulating evidence suggests that miR-675-5p plays important roles in human carcinogenesis. However, its precise biological role remains largely elusive. This study examined the role of miR-675-5p in non- small cell lung cancer (NSCLC).MethodsThe expression of miR-675-5p was analyzed by real-time quantitative PCR (qRT-PCR). The effect of miR-675-5p on proliferation was evaluated through MTT and colony formation assays, and cell migration and invasion were evaluated through transwell assays. The expression of target proteins and downstream molecules was analyzed by western blotting and immunohistochemical staining. The luciferase reporter assay was used to assess the target genes of miR-675-5p in non-small cell lung cancer cells.ResultsThe expression levels of miR-675-5p in NSCLC tissues were significantly reduced compared to those in adjacent non-cancerous tissues (P < 0.001). The expression of miR-675-5p in patients with non-small cell lung cancer had a negative correlation with lymph node metastasis (P < 0.01) and TNM stage (P < 0.05). Down-regulation of miR-675-5p promoted cell growth, proliferation, colony formation, invasion and migration, and promoted the tumorigenicity graft growth of nude mice in vivo (P < 0.01); whereas up-regulation of miR-675-5p had the contrary effects. The luciferase reporter assay showed that GPR55 was a direct target gene of miR-675-5p. Overexpression of miR-675-5p can lead to the down-regulation of GPR55 and its signaling pathway, whereas the effect can be reversed by down-regulation of miR-675-5p expression.ConclusionsmiR-675-5p functions as a novel tumor suppressor in NSCLC and the anti-oncogenic activity may involve its inhibition of the target gene GPR55. These findings suggest the possibility for miR-675-5p as a therapeutic target in NSCLC.

【 授权许可】

Unknown   
© He et al.; licensee BioMed Central. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.