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

[ Vol. 16 , Issue. 4 ]

Author(s):

Lin Liu, Wei Zheng, Yang Song, Xiaohui Du, Yun Tang, Jing Nie and Weidong Han   Pages 310 - 315 ( 6 )

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.

Keywords:

5-FU, colorectal cancer, drug sensitivity, miRNA-497, neoadjuvant chemotherapy, Smurf1.

Affiliation:

Department of Molecular Biology, General Hospital of PLA, 28 Fuxing Road, Beijing 100853, China.



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