Targeting miR-21 enhances the sensitivity of human colon cancer HT-29 cells to chemoradiotherapy in vitro
Targeting miR-21 enhances the sensitivity of human colon cancer HT-29 cells to chemoradiotherapy in vitro
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靶向 miR-21 可增强人结肠癌 HT-29 细胞对体外放化疗的敏感性。
DOI：
10.1016/j.bbrc.2013.11.064
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发表时间：
2014-01-17
影响因子：
3.1
通讯作者：
Xiong, Jian-Ping
中科院分区：
文献类型：
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作者：
Deng, Jun;Lei, Wan;Xiong, Jian-Ping
5-氟尿嘧啶(5-FU)是一种经典的化疗药物，已被广泛用于结直肠癌的治疗，但结直肠癌细胞对原始或获得性5-FU治疗往往耐药。多项研究表明，miR-21在结直肠癌中显著升高。这表明这种miRNA可能在这种抗性中发挥了作用。在这项研究中，我们研究了这种可能性以及这种作用背后的可能机制。结果表明，强制表达miR-21显著抑制了HT-29结肠癌细胞的凋亡，增强了细胞的增殖、侵袭和集落形成能力，促进了G1/S细胞周期转换，增强了肿瘤细胞对5-FU和X线的耐受性。此外，miR-21基因敲除逆转了对HT-29细胞的上述作用，并增加了HT-29/5-FU对5-FU化疗的敏感性。最后，我们发现miR-21靶向人类MutS同源基因2(HMSH2)，并间接调节胸苷磷酸化酶(TP)和二氢嘧啶脱氢酶(DPD)的表达。这些结果表明miR-21可能在结肠癌细胞对5-FU耐药中起重要作用。(C)2014年，爱思唯尔公司出版。
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. (C) 2014 Published by Elsevier Inc.