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circ_SIRT1 upregulates ATG12 to facilitate Imatinib resistance in CML through interacting with EIF4A3

Rong Zhang1, Jinjin Hao1, Hui Yu1

  • 1Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

Gene
|October 22, 2023
PubMed

Insights

A novel circular RNA, circ_SIRT1, is upregulated in imatinib-resistant chronic myeloid leukemia (CML). Inhibiting circ_SIRT1 may overcome drug resistance by targeting autophagy and EIF4A3, offering new therapeutic strategies for CML patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Imatinib is a standard treatment for chronic myeloid leukemia (CML).
  • Drug resistance to imatinib limits treatment efficacy in CML.
  • Circular RNAs (circRNAs) play roles in cancer progression and drug resistance.

Purpose of the Study:

  • To identify novel therapeutic targets for imatinib-resistant CML.
  • To investigate the role of circ_SIRT1 in CML drug resistance.

Main Methods:

  • Identified circ_SIRT1 expression in CML.
  • Knocked down circ_SIRT1 in K562/R cells.
  • Assessed cell viability, invasion, apoptosis, and autophagy.
  • Investigated the interaction between circ_SIRT1, EIF4A3, and ATG12.

Main Results:

  • circ_SIRT1 is upregulated in CML and correlated with drug resistance.
  • circ_SIRT1 knockdown reduced cell viability, invasion, and enhanced apoptosis in K562/R cells.
  • circ_SIRT1 inhibition attenuated autophagy and decreased imatinib resistance.
  • circ_SIRT1 directly binds EIF4A3, regulating ATG12 transcription and affecting autophagy and imatinib resistance.

Conclusions:

  • circ_SIRT1 acts as a tumor regulator in CML.
  • circ_SIRT1 influences imatinib resistance through the EIF4A3-ATG12 pathway.
  • circ_SIRT1 represents a potential therapeutic target for imatinib-resistant CML.
Keywords:
ATG12CMLEIF4A3Imatinib resistancecirc_SIRT1

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