title: Overexpression of Gremlin promotes non-small cell lung cancer progression.
abstract: Lung cancer is the major cause of cancer-related death worldwide, and 80 % of them are non-small cell lung cancer (NSCLC) cases. Gremlin, a bone morphogenetic protein (BMP) antagonist, is overexpressed in various cancerous tissues; however, little is known about the roles of Gremlin in lung carcinogenesis, and it remains unclear whether Gremlin expression may associate with EGFR-TKI resistance. In this study, expression of Gremlin mRNA and protein in matched tumor and normal lung specimens are quantified by quantitative real-time PCR and western blot. The functional role of Gremlin in NSCLC cells was evaluated by interference RNA (siRNA). The effects of Silenced Gremlin on the resistant PC-9/GR cell line were investigated by proliferation and apoptosis analysis compared with control PC-9 cells. Our results found that Gremlin expression levels were higher in NSCLC tissues, and Gremlin was more highly expressed in PC-9/GR cells compared to PC-9 cells. Knocking down of Gremlin in PC-9/GR cells decreased cell proliferation and increased the expression of BMP7 protein. In addition, Gremlin silencing significantly potentiated apoptosis induced by gefitinib in PC-9/GR with Gremlin knockdown compared to PC-9 transfected with control shRNA, suggesting Gremlin contributes to gefitinib resistance in NSCLC. Gremlin might be explored as a candidate of therapeutic target for modulating EGFR-TKI sensitivity in NSCLC.
authors.affiliation: Department of Respiratory Medicine, Qilu Hospital of Shandong University, Jinan, 250012, China.
authors.forename: Yunhong
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Clinical Laboratory, Qianfoshan Hospital of Shandong Province, Jinan, 250012, China.
authors.forename: Yie
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Yinan Branch of Qilu Hospital of Shandong University, Yinan, 276300, China.
authors.forename: Liyun
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Respiratory Medicine, Qilu Hospital of Shandong University, Jinan, 250012, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Respiratory Medicine, Qilu Hospital of Shandong University, Jinan, 250012, China.
authors.forename: Chunyu
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Respiratory Medicine, Qilu Hospital of Shandong University, Jinan, 250012, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Respiratory Medicine, Qilu Hospital of Shandong University, Jinan, 250012, China. yiqing_qu@126.com.
authors.forename: Yiqing
authors.initials: Y
authors.lastname: Qu
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D055419:Bone Morphogenetic Protein 7 / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D018450:Disease Progression; D066246:ErbB Receptors / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7; D036341:Intercellular Signaling Peptides and Proteins; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D066246:ErbB Receptors
keywords: Apoptosis; Chemoresistance; EGFR-TKI; Gremlin; Lung cancer; NSCLC; PC-9/GR cells; Proliferation