Wu D-W, Hsu N-Y, Wang Y-C, Lee M-C, Cheng Y-W, Chen C-Y, Lee H
Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
1] School of Medicine, Chung Shan Medical University, Taichung, Taiwan [2] Department of Chest Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan.
Oncogene. 2015 Apr 16;34(16):2072-82. doi: 10.1038/onc.2014.152. Epub 2014 Jun 9.
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.
已有报道称微小RNA-29（miR-29）家族在实体瘤的肿瘤进展和转移中具有双重作用。关于miR-29在肿瘤恶性程度中的作用及其在非小细胞肺癌（NSCLC）总生存期（OS）和无复发生存期（RFS）中的预后价值，相关证据仍存在矛盾。本文所呈现的机制研究表明，c-Myc抑制miR-29b的表达，促进肺癌细胞在软琼脂中的生长和侵袭能力。有趣的是，c-Myc导致的miR-29b表达降低是由启动子甲基化导致的FHIT缺失所介导的软琼脂生长和侵袭性的原因。在患者中，与低c-Myc表达的肿瘤相比，高c-Myc表达的肿瘤中miR-29b和FHIT的低表达更为常见。Kaplan-Meier和Cox回归分析表明，高c-Myc、低miR-29b和低FHIT表达的肿瘤的OS和RFS期比其对应肿瘤更短。总之，c-Myc导致的miR-29b表达降低可能是FHIT缺失介导的肿瘤侵袭性以及NSCLC患者不良预后的原因。因此，我们建议使用c-Myc抑制剂恢复miR-29b的表达可能有助于抑制FHIT缺失介导的肿瘤侵袭性，从而改善FHIT低表达肿瘤的NSCLC患者的预后。
