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: D-W Wu, N-Y Hsu, Y-C Wang, M-C Lee, Y-W Cheng, C-Y Chen, H Lee
• Journal: Oncogene (Oncogene) Vol. 34 Issue 16 Pg. 2072-82 (Apr 16 2015) ISSN: 1476-5594 [Electronic] England
• PMID: 24909176 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• MIRN29a microRNA, human
• MYC protein, human
• MicroRNAs
• Neoplasm Proteins
• Proto-Oncogene Proteins c-myc
• fragile histidine triad protein
• Acid Anhydride Hydrolases

Topics

• Acid Anhydride Hydrolases (biosynthesis, genetics)
• Carcinoma, Non-Small-Cell Lung (genetics, pathology)
• Cell Line, Tumor
• Cell Movement (genetics)
• DNA Methylation
• Disease-Free Survival
• Gene Expression Regulation, Neoplastic
• Humans
• Lung Neoplasms (genetics, pathology)
• MicroRNAs (biosynthesis, genetics)
• Neoplasm Invasiveness
• Neoplasm Proteins (biosynthesis, genetics)
• Neoplasm Recurrence, Local
• Promoter Regions, Genetic (genetics)
• Proto-Oncogene Proteins c-myc (antagonists & inhibitors, biosynthesis)
• Signal Transduction (genetics)