title: miR-186 downregulation correlates with poor survival in lung adenocarcinoma, where it interferes with cell-cycle regulation.
abstract: Deeper mechanistic understanding of lung adenocarcinoma (non-small cell lung carcinoma, or NSCLC), a leading cause of cancer-related deaths overall, may lead to more effective therapeutic strategies. In analyzing NSCLC clinical specimens and cell lines, we discovered a uniform decrease in miR-186 (MIR186) expression in comparison with normal lung tissue or epithelial cell lines. miR-186 expression correlated with patient survival, with median overall survival time of 63.0 or 21.5 months in cases exhibiting high or low levels of miR-186, respectively. Enforced overexpression of miR-186 in NSCLC cells inhibited proliferation by inducing G(1)-S checkpoint arrest. Conversely, RNA interference-mediated silencing miR-186 expression promoted cell-cycle progression and accelerated the proliferation of NSCLC cells. Cyclin D1 (CCND1), cyclin-dependent kinase (CDK)2, and CDK6 were each directly targeted for inhibition by miR-186 and restoring their expression reversed miR-186-mediated inhibition of cell-cycle progression. The inverse relationship between expression of miR-186 and its targets was confirmed in NSCLC tumor xenografts and clinical specimens. Taken together, our findings established a tumor-suppressive role for miR-186 in the progression of NSCLC.
authors.affiliation: Department of Microbiology, Zhongshan School of Medicine; Key Laboratory of Tropical Disease Control, Sun Yat-Sen University, Guangzhou, Guangdong, China.
authors.forename: Junchao
authors.initials: J
authors.lastname: Cai
authors.forename: Jueheng
authors.initials: J
authors.lastname: Wu
authors.forename: Huizhong
authors.initials: H
authors.lastname: Zhang
authors.forename: Lishan
authors.initials: L
authors.lastname: Fang
authors.forename: Yongbo
authors.initials: Y
authors.lastname: Huang
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.forename: Xun
authors.initials: X
authors.lastname: Zhu
authors.forename: Rong
authors.initials: R
authors.lastname: Li
authors.forename: Mengfeng
authors.initials: M
authors.lastname: Li
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality; D000077192:Adenocarcinoma of Lung; D002453:Cell Cycle; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000378:metabolism; D056742:Cyclin D2 / Q000378:metabolism; D051361:Cyclin-Dependent Kinase 6 / Q000378:metabolism; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality; D035683:MicroRNAs / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology
chemical_list: C080336:CCND2 protein, human; D056742:Cyclin D2; C571522:MIRN1186 microRNA, mouse; D035683:MicroRNAs; D034741:RNA, Small Interfering; D019938:Cyclin D1; D051361:Cyclin-Dependent Kinase 6