Targeting miR-21 enhances the sensitivity of human colon cancer HT-29 cells to chemoradiotherapy in vitro |
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Authors: | Jun Deng Wan Lei Jian-Chun Fu Ling Zhang Jun-He LiJian-Ping Xiong |
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Affiliation: | Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, PR China |
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Abstract: | 5-Fluorouracil (5-FU) is a classic chemotherapeutic drug that has been widely used for colorectal cancer treatment, but colorectal cancer cells are often resistant to primary or acquired 5-FU therapy. Several studies have shown that miR-21 is significantly elevated in colorectal cancer. This suggests that this miRNA might play a role in this resistance. In this study, we investigated this possibility and the possible mechanism underlying this role. We showed that forced expression of miR-21 significantly inhibited apoptosis, enhanced cell proliferation, invasion, and colony formation ability, promoted G1/S cell cycle transition and increased the resistance of tumor cells to 5-FU and X radiation in HT-29 colon cancer cells. Furthermore, knockdown of miR-21 reversed these effects on HT-29 cells and increased the sensitivity of HT-29/5-FU to 5-FU chemotherapy. Finally, we showed that miR-21 targeted the human mutS homolog2 (hMSH2), and indirectly regulated the expression of thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD). These results demonstrate that miR-21 may play an important role in the 5-FU resistance of colon cancer cells. |
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Keywords: | CRC, colorectal cancer qRT-PCR, quantitative real time polymerase chain reaction TS, thymidylate synthase TP, thymidine phosphorylase DPD, dihydropyrimidine dehydrogenase MMR, mismatch repair system UTR, untranslated regions NC, nonsense control |
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