title: c-Myc suppresses microRNA-29b to promote tumor aggressiveness and poor outcomes in non-small cell lung cancer by targeting FHIT.
abstract: The dual role of the microRNA-29 (miR-29) family in tumor progression and metastasis in solid tumors has been reported. Evidence for the role of miR-29 in tumor malignancy and its prognostic value in overall survival (OS) and relapse-free survival (RFS) in non-small cell lung cancer (NSCLC) remains conflicting. Mechanistic studies presented herein demonstrated that c-Myc suppressed the expression of miR-29b, promoting soft agar growth and invasion capability in lung cancer cells. Interestingly, the decrease in the expression of miR-29b by c-Myc is responsible for soft agar growth and invasiveness mediated by FHIT loss due to promoter methylation. Among patients, low expression of miR-29b and FHIT was more common in tumors with high c-Myc expression than in tumors with low c-Myc expression. Kaplan-Meier and Cox regression analysis showed that tumors with high c-Myc, low miR-29b and low FHIT expression had shorter OS and RFS periods than their counterparts. In conclusion, the decrease in the expression of miR-29b by c-Myc may be responsible for FHIT loss-mediated tumor aggressiveness and for poor outcome in NSCLC. Therefore, we suggest that restoration of the miR-29b expression using the c-Myc inhibitor might be helpful in suppressing tumor aggressiveness mediated by FHIT loss and consequently improving outcomes in NSCLC patients with tumors with low expression of FHIT.
authors.affiliation: Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
authors.forename: D-W
authors.initials: DW
authors.lastname: Wu
authors.affiliation: Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
authors.forename: N-Y
authors.initials: NY
authors.lastname: Hsu
authors.affiliation: 1] School of Medicine, Chung Shan Medical University, Taichung, Taiwan [2] Department of Chest Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Y-C
authors.initials: YC
authors.lastname: Wang
authors.affiliation: Department of Thoracic Surgery, Taichung Veteran General Hospital, Taichung, Taiwan.
authors.forename: M-C
authors.initials: MC
authors.lastname: Lee
authors.affiliation: Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
authors.forename: Y-W
authors.initials: YW
authors.lastname: Cheng
authors.affiliation: Department of Surgery, China Medical University Hospital, Taichung, Taiwan.
authors.forename: C-Y
authors.initials: CY
authors.lastname: Chen
authors.affiliation: Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
authors.forename: H
authors.initials: H
authors.lastname: Lee
mesh_terms: D017766:Acid Anhydride Hydrolases / Q000096:biosynthesis* / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D019175:DNA Methylation; D018572:Disease-Free Survival; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology*; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D009364:Neoplasm Recurrence, Local; D011401:Promoter Regions, Genetic / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D015398:Signal Transduction / Q000235:genetics; D000099170:Bis(5'-adenosyl)triphosphatase
chemical_list: D017766:Acid Anhydride Hydrolases; D035683:MicroRNAs; D009363:Neoplasm Proteins; D016271:Proto-Oncogene Proteins c-myc; D000099170:Bis(5'-adenosyl)triphosphatase; C532045:MIRN29a microRNA, human; C489427:MYC protein, human