miRNA-497 Enhances the Sensitivity of Colorectal Cancer Cells to Neoadjuvant Chemotherapeutic Drug.
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.
Lin
L
Liu
Wei
W
Zheng
Yang
Y
Song
Xiaohui
X
Du
Yun
Y
Tang
Jing
J
Nie
Department of Molecular Biology, General Hospital of PLA, 28 Fuxing Road, Beijing 100853, China. hanwdrsw69@yahoo.com.
Weidong
W
Han
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D015536:Down-Regulation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics*; D005472:Fluorouracil / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D020360:Neoadjuvant Therapy; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C559640:MIRN497 microRNA, human; D035683:MicroRNAs; C498342:SMURF1 protein, human; D044767:Ubiquitin-Protein Ligases; D005472:Fluorouracil