c-Myc suppresses microRNA-29b to promote tumor aggressiveness and poor outcomes in non-small cell lung cancer by targeting FHIT

• Published in: Oncogene Vol. 34; no. 16; pp. 2072 - 2082
• Main Authors: Wu, D-W, Hsu, N-Y, Wang, Y-C, Lee, M-C, Cheng, Y-W, Chen, C-Y, Lee, H
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 16.04.2015; Nature Publishing Group
• Subjects: 692/420/755; 692/699/67/1612/1350; 692/700/1750; Acid Anhydride Hydrolases - biosynthesis; Acid Anhydride Hydrolases - genetics; Apoptosis; c-Myc protein; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - pathology; Cell Biology; Cell Line, Tumor; Cell Movement - genetics; Development and progression; Disease-Free Survival; DNA Methylation; Enzymes; Gene expression; Gene Expression Regulation, Neoplastic; Genetic aspects; Health aspects; Human Genetics; Humans; Internal Medicine; Invasiveness; Lung cancer; Lung cancer, Non-small cell; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Malignancy; Medicine; Medicine & Public Health; Metastases; Metastasis; MicroRNA; MicroRNAs; MicroRNAs - biosynthesis; MicroRNAs - genetics; miRNA; Myc protein; Neoplasm Invasiveness; Neoplasm Proteins - biosynthesis; Neoplasm Proteins - genetics; Neoplasm Recurrence, Local; Non-small cell lung carcinoma; Oncology; original-article; Promoter Regions, Genetic - genetics; Proto-Oncogene Proteins c-myc - antagonists & inhibitors; Proto-Oncogene Proteins c-myc - biosynthesis; Regulation; Signal Transduction - genetics; Small cell lung carcinoma; Solid tumors; Tumors
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/onc.2014.152

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.