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