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.

结直肠癌的耐药性是临床上的一大挑战。阐明耐药背后的深层机制，将对结直肠癌患者的诊断、治疗和预后有很大的帮助。在这项研究中，miR-29b-3p 被证明参与了对 5-氟尿嘧啶 (5-FU) 诱导的结直肠癌坏死性凋亡的抵抗。此外，miR-29b-3p 显示靶向坏死性凋亡 TRAF5 的调节亚基。拯救TRAF5可以逆转miR-29b-3p对5-FU诱导的坏死性凋亡的作用，这与necrostatin-1（一种特异性坏死性凋亡抑制剂）的作用一致。然后证明miR-29b-3p与结直肠癌的化学抗性呈正相关，而TRAF5呈负相关。综上所述，推测miR-29b-3p/TRAF5信号轴通过调节坏死性凋亡在结直肠癌患者化疗耐药中起关键作用。本研究的结果为我们提供了一个新的结直肠癌干扰治疗靶点。