miRNA-497 Enhances the Sensitivity of Colorectal Cancer Cells to Neoadjuvant Chemotherapeutic Drug.

Abstract

The neoadjuvant therapy has significantly improved the outcome of locally advanced resectable T3 rectal cancer patients. Actually, only a portion of patients show sensitivity to the preoperative chemoradiation and benefit markedly from this treatment. However, biomarkers for predicting neoadjuvant therapy sensitivity remain unclear. In this study, through screening of a series of microRNAs dysregulated in colorectal cancer patients, we observed that miRNA-497 expression was downregulated in tumor tissues of neoadjuvant chemotherapy responders as compared to that in non-responders. MiRNA-497 level was correlated with chemotherapeutic drug 5-fluorouracil (5-FU) sensitivity in colorectal cancer cells. Functional studies showed that restoration of miRNA-497 expression inhibited cell viability and enhanced 5-FU sensitivity in SW480 cells. By contrast, miRNA inhibitors-mediated silence of miRNA-497 promoted cell growth and reduced the sensitivity of LoVo cells to 5-FU. In addition, miRNA-497 targeted Smurf1 in CRC cells and the Smurf1 expression level was dramatically increased in neoadjuvant therapy-resistant patients compared with treatment-sensitive patients. These results indicate that down-regulation of miRNA-497 in colorectal cancer may contribute to the resistance of CRC cells to 5-FU treatment. Thus, miRNA-497 has the potential to be a novel biomarker for predicting the neoadjuvant chemotherapy sensitivity in CRC patients.

• Authors: Lin Liu, Wei Zheng, Yang Song, Xiaohui Du, Yun Tang, Jing Nie, Weidong Han
• Journal: Current protein & peptide science (Curr Protein Pept Sci) Vol. 16 Issue 4 Pg. 310-5 ( 2015) ISSN: 1875-5550 [Electronic] United Arab Emirates
• PMID: 25929865 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Biomarkers, Tumor
• MIRN497 microRNA, human
• MicroRNAs
• SMURF1 protein, human
• Ubiquitin-Protein Ligases
• Fluorouracil

Topics

• Antineoplastic Agents (pharmacology, therapeutic use)
• Biomarkers, Tumor (genetics)
• Cell Line, Tumor
• Cell Proliferation (drug effects, genetics)
• Colorectal Neoplasms (drug therapy, genetics, pathology)
• Down-Regulation (drug effects)
• Drug Resistance, Neoplasm (drug effects, genetics)
• Fluorouracil (pharmacology, therapeutic use)
• Humans
• MicroRNAs (genetics)
• Neoadjuvant Therapy
• Ubiquitin-Protein Ligases (metabolism)