title: FOXP4 modulates tumor growth and independently associates with miR-138 in non-small cell lung cancer cells.
abstract: Family of forkhead box transcription factors, including forkhead box P4 (FOXP4), plays an important role in oncogenesis. The current study is to evaluate the role of FOXP4 in regulating human non-small cell lung cancer (NSCLC). Quantitative RT-PCR and Western blot were performed to evaluate the gene and protein expressions of FOXP4 in six NSCLC cell lines and 55 NSCLC patients. Lentivirus of small hairpin RNA (FOXP4-shRNA) was used to downregulate FOXP4 in NSCLC cell lines A549 and H1703 cells. Its effect on NSCLC growth, invasion, and cell cycle were evaluated by cell proliferation assay, migration assay, and cell cycle assay, respectively. Dual luciferase assay and Western blot were used to examine whether microRNA-138 (miR-138) was an upstream regulator of FOXP4. The dependence of FOXP4 on miR-138 associated signaling pathway was evaluated by ectopically overexpressing enhancer of zeste homolog 2 (EZH2), a known miR-138 target in NSCLC. FOXP4 was highly expressed in both NSCLC cell lines and NSCLC patients. FOXP4 downregulation by FOXP4-shRNA markedly reduced cancer cell growth and invasion, as well as induced cell cycle arrest in A549 and H1703 cells. MiR-138 was confirmed to be an upstream regulator of FOXP4 and directly regulated FOXP4 expression in A549 and H1703 cells. FOXP4 downregulation-mediated inhibition on cancer cell growth and invasion was independent on overexpressing EZH2, another direct target of miR-138 in NSCLC. Our data demonstrated that FOXP4 was a critical regulator in NSCLC and independently associated with miR-138 regulation.
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital, Medical College of Xi'an Jiaotong University, 277 West Yanta Road, Xian, 710061, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Yang
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital, Medical College of Xi'an Jiaotong University, 277 West Yanta Road, Xian, 710061, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital, Medical College of Xi'an Jiaotong University, 277 West Yanta Road, Xian, 710061, China.
authors.forename: Asmitananda
authors.initials: A
authors.lastname: Thakur
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital, Medical College of Xi'an Jiaotong University, 277 West Yanta Road, Xian, 710061, China.
authors.forename: Tianjun
authors.initials: T
authors.lastname: Chen
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital, Medical College of Xi'an Jiaotong University, 277 West Yanta Road, Xian, 710061, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xue
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital, Medical College of Xi'an Jiaotong University, 277 West Yanta Road, Xian, 710061, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital, Medical College of Xi'an Jiaotong University, 277 West Yanta Road, Xian, 710061, China. mingweic2@aol.com.
authors.forename: Mingwei
authors.initials: M
authors.lastname: Chen
mesh_terms: D020413:3' Untranslated Regions; D017209:Apoptosis; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle; D002465:Cell Movement; D049109:Cell Proliferation; D051858:Forkhead Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008168:Lung / Q000378:metabolism*; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D035683:MicroRNAs / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D020413:3' Untranslated Regions; C576732:FOXP4 protein, human; D051858:Forkhead Transcription Factors; C546110:MIRN138 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D034741:RNA, Small Interfering
keywords: Cancer growth; Cancer migration; EZH2; FOXP4; NSCLC; miR-138