MicroRNA-29b-3p promotes 5-fluorouracil resistance <em>via</em> suppressing TRAF5-mediated necroptosis in human colorectal cancer

MicroRNA-29b-3p 通过抑制人类结直肠癌中的 TRAF5 介导的坏死性凋亡来促进 5-氟尿嘧啶耐药性

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作者:Shuimei Wu, Yun Zhou, Ping Liu, Hui Zhang, Wanliang Wang, Yuan Fang, Xiang Shen

Abstract

Drug resistance in colorectal cancer is a great challenge in clinic. Elucidating the deep mechanism underlying drug resistance will bring much benefit to diagnosis, therapy and prognosis in patients with colorectal cancer. In this study, miR-29b-3p was shown to be involved in resistance to 5-fluorouracil (5-FU)-induced necroptosis of colorectal cancer. Further, miR-29b-3p was shown to target a regulatory subunit of necroptosis TRAF5. Rescue of TRAF5 could reverse the effect of miR-29b-3p on 5-FU-induced necroptosis, which was consistent with the role ofnecrostatin-1 (a specific necroptosis inhibitor). Then it was demonstrated that miR-29b-3p was positively correlated with chemo-resistance in colorectal cancer while TRAF5 negatively. In conclusion, it is deduced that miR-29b-3p/TRAF5 signaling axis plays critical role in drug resistance in chemotherapy for colorectal cancer patients by regulating necroptosis. The findings in this study provide us a new target for interfere therapy in colorectal cancer.

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