title: miR-592 functions as a tumor suppressor in human non-small cell lung cancer by targeting SOX9.
abstract: A growing body of evidence suggests that microRNA-592 (miR-592) may be involved in the initiation and progression of cancer by targeting various molecules in several human cancers. However, the function and underlying molecular mechanism of miR-592 in non-small cell lung cancer (NSCLC) remains unclear. In the present study, we found that miR-592 was significantly downregulated in NSCLC cell lines and tissues by real-time quantitative RT-PCR (qRT-PCR), and that lower miR-592 expression was negatively associated with advanced tumor/nodes/metastasis (TNM) classification stages (P<0.01) and lymph node metastasis (P<0.01). Function assay demonstrated that the miR-592 mimic reduced in vitro cell proliferation, colony formation, migration and invasion in A549 cells (a NSCLC-derived cell line), and inhibited in vivo tumor cell growth in xenografted nude mice. Furthermore, the gender determining region Y (SRY)-related high mobility group box 9 (SOX9) was confirmed as a direct target of miR-592, using luciferase reporter, qRT-PCR and western blot assays. Enforced overexpression of SOX9 effectively reversed the tumor suppressive functions of miR-592 on NSCLC proliferation, colony formation, migration and invasion. These findings suggested that miR-592 functions as tumor suppressor in NSCLC by suppressing the activity of SOX9, and that miR-592 might serve as a promising therapeutic target for NSCLC treatment.
authors.affiliation: Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Colorectal and Anal Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Bai
authors.initials: B
authors.lastname: Li
authors.affiliation: Operating Room, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Niu
authors.affiliation: Department of Anesthesiology, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Ge
mesh_terms: D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D055758:SOX9 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: C000588991:MIRN592 microRNA, human; D035683:MicroRNAs; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human