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

Eur J Histochem. 2021 Jun 22;65(2):3247. doi: 10.4081/ejh.2021.3247.


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.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / metabolism*
  • Drug Resistance, Neoplasm / physiology*
  • Fluorouracil / pharmacology
  • Fluorouracil / therapeutic use*
  • Gene Expression Regulation, Neoplastic / physiology
  • Gene Knockdown Techniques
  • Humans
  • Mice, Inbred BALB C
  • Mice, Inbred NOD
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Necroptosis / physiology*
  • TNF Receptor-Associated Factor 5 / genetics
  • TNF Receptor-Associated Factor 5 / metabolism*


  • MIRN29a microRNA, human
  • MicroRNAs
  • TNF Receptor-Associated Factor 5
  • TRAF5 protein, human
  • Fluorouracil

Grant support

Funding:This work was supported by the Wuhu Health commission Research Project