title: MicroRNA-663a is downregulated in non-small cell lung cancer and inhibits proliferation and invasion by targeting JunD.
abstract: MicroRNA-663a expression is downregulated in several tumors. However, its functions and mechanisms in human non-small cell lung (NSCLC) cancer remain obscure. The present study aimed to identify the expression pattern, biological roles and potential mechanisms by which miR-663a dysregulation is associated with NSCLC.
  
  
  
  We examined expression level of miR-663a in 62 cases of NSCLC tissues and 5 NSCLC cell lines by reverse transcription PCR. In vitro, gain-of-function and loss-of-function experiments were performed to examine the impact of miR-663a on proliferation, cell cycle progression and invasion of NSCLC cells. Using fluorescence reporter assays, we also explored the potential targets and possible mechanisms of miR-663a in NSCLC cells.
  
  
  
  Downregulation of miR-663a was observed in 42 of 62 of lung cancer tissues compared with paired normal tissues (mean cancer/normal value = 0.745) and its downregulation correlated with nodal metastasis. Transfection of miR-663a mimic suppressed cell proliferation, cell cycle progression and invasion, with downregulation of cyclin D1, cyclin E and MMP9 in both H460 and H1299 cell lines. Transfection of miR-663a inhibitor in both H460 and H1299 cell lines exhibited the opposite effects. In addition, we confirmed that miR-663a could inhibit AP-1 activity and AP-1 component JunD was a direct target of miR-663a in lung cancer cells. Transfection of miR-663a mimic downregulated JunD expression. In addition, JunD siRNA treatment abrogated miR-663a inhibitor-induced expression of cyclin D1, cyclin E and MMP9. Above all, both miRNA mimic and inhibitor in two different NSCLC cell lines demonstrated that miR-663a inhibits proliferation and invasion by targeting AP-1 transcription factor JunD.
  
  
  
  This study indicates that miR-663a downregulation might be associated with NSCLC progression. MiR-663a suppresses proliferation and invasion by targeting AP-1 component JunD in NSCLC cells.
authors.affiliation: Department of Geriatrics, Shengjing Hospital of China Medical University, 36 Sanhao Road, Shenyang, 110004, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Medicine, Shengjing Hospital of China Medical University, Shenyang, China.
authors.forename: Xiaoman
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Geriatrics, Shengjing Hospital of China Medical University, 36 Sanhao Road, Shenyang, 110004, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Geriatrics, Shengjing Hospital of China Medical University, 36 Sanhao Road, Shenyang, 110004, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Geriatrics, Shengjing Hospital of China Medical University, 36 Sanhao Road, Shenyang, 110004, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Bai
authors.affiliation: Department of Geriatrics, Shengjing Hospital of China Medical University, 36 Sanhao Road, Shenyang, 110004, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Geriatrics, Shengjing Hospital of China Medical University, 36 Sanhao Road, Shenyang, 110004, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Kan
authors.affiliation: Department of Geriatrics, Shengjing Hospital of China Medical University, 36 Sanhao Road, Shenyang, 110004, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Geriatrics, Shengjing Hospital of China Medical University, 36 Sanhao Road, Shenyang, 110004, China.
authors.forename: Huiyan
authors.initials: H
authors.lastname: Niu
authors.affiliation: Department of Geriatrics, Shengjing Hospital of China Medical University, 36 Sanhao Road, Shenyang, 110004, China. hepingcmu@126.com.
authors.forename: Ping
authors.initials: P
authors.lastname: He
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000502:physiology*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference
chemical_list: C559371:JunD protein, human; C552243:MIRN663 microRNA, human; D035683:MicroRNAs; D016755:Proto-Oncogene Proteins c-jun
keywords: Invasion; JunD; Lung cancer; Proliferation; miR-663a