Related Experiment Video

Updated: Aug 10, 2026

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
10:44

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs

Published on: May 15, 2019

tRNA-derived fragment tRF-17-8SPOL52 induces resistance to bortezomib in multiple myeloma via autophagy activation

Yunfeng Fu1, Zhenrong Qiao2, Yulian Xiao2

  • 1Department of Hematology, The Third Xiangya Hospital of Central South University, Changsha, 410000, China; Department of Blood Transfusion, The Third Xiangya Hospital of Central South University, Changsha, 410000, China.

Biochimica Et Biophysica Acta. Molecular Basis of Disease
|August 4, 2026
PubMed

Insights

A specific tRNA-derived fragment, tRF-17-8SPOL52, promotes bortezomib resistance in multiple myeloma by increasing autophagy. This occurs through the inhibition of RUBCN, offering potential therapeutic targets for overcoming drug resistance.

Area of Science:

  • Molecular Biology
  • Oncology
  • Genetics

Background:

  • Drug resistance, particularly to bortezomib, significantly impacts multiple myeloma patient survival.
  • The role of tRNA-derived fragments (tsRNAs) in mediating this resistance is not well understood.

Purpose of the Study:

  • To identify and characterize tsRNAs involved in bortezomib resistance in multiple myeloma.
  • To elucidate the molecular mechanism by which a specific tsRNA contributes to drug resistance.

Main Methods:

  • Screening for upregulated tsRNAs in relapsed/refractory myeloma.
  • Utilizing RNA interference, Ago-RIP-sequencing, and dual-luciferase reporter assays.
  • Investigating the role of autophagy and RUBCN regulation via overexpression, inhibition, and rescue experiments.

Main Results:

  • tRF-17-8SPOL52 was identified as the most significantly upregulated tsRNA in relapsed/refractory myeloma.
  • tRF-17-8SPOL52 was found to promote bortezomib resistance both in vitro and in vivo.
  • tRF-17-8SPOL52 negatively regulates RUBCN in an Argonaute-dependent manner, leading to increased autophagy and subsequent bortezomib resistance.

Conclusions:

  • tRF-17-8SPOL52 is a key mediator of bortezomib resistance in multiple myeloma.
  • The mechanism involves the promotion of autophagy via RUBCN inhibition.
  • Targeting tRF-17-8SPOL52 or its downstream pathways may offer novel therapeutic strategies.
Keywords:
AutophagyBiomarkerDrug resistanceMultiple myelomatRNA-derived fragments

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