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MicroRNA-9-5p increases the sensitivity of colorectal cancer cells to 5-fluorouracil by downregulating high mobility group A2 expression
Authors:Huizhe Zheng  Bin Yan  Qi Wu  Jingli Zhang
Affiliation:1.Department of Pathology, Hongqi Hospital Affiliated to Mudanjiang Medical University, Mudanjiang, Heilongjiang 157011, P.R. China;2.Key Laboratory of Tumor Prevention and Treatment of Heilongjiang Province, Mudanjiang Medical University, Mudanjiang, Heilongjiang 157011, P.R. China;3.Department of Rheumatology and Immunology, Hongqi Hospital Affiliated to Mudanjiang Medical University, Mudanjiang, Heilongjiang 157011, P.R. China
Abstract:Chemotherapy drug 5-fluorouracil (5-FU) is the first-line treatment for colorectal cancer (CRC); however, 5-FU resistance decreases CRC therapeutic efficiency. A previous study revealed that microRNA (miR)-9-5p serves an antitumor effect in CRC. However, the effect of miR-9-5p in CRC chemoresistance remains unknown. In the present study, two CRC cell lines, including HT-29 and HCT-116 cells, were used to investigate the impact of miR-9-5p in overcoming 5-FU resistance. The results revealed that treatment with 5-FU decreased CRC cell viability and upregulated miR-9-5p expression in both CRC cells. Knockdown of miR-9-5p decreased HCT-116 cell sensitivity to 5-FU and inhibited apoptosis. By contrast, miR-9-5p overexpression enhanced the sensitivity of HT-29 cells to 5-FU and induced apoptosis. Additionally, it was confirmed that miR-9-5p directly targeted high mobility group A2 (HMGA2). HMGA2 overexpression reversed miR-9-5p-induced HT-29 apoptosis. The present study indicated that miR-9-5p enhanced the sensitivity of CRC cells to 5-FU via downregulating HMGA2 expression.
Keywords:colorectal cancer   5-fluorouracil resistance   microRNA-9-5p   high mobility group A2   apoptosis
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