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miRNA-381 regulates renal cancer stem cell properties and sunitinib resistance via targeting SOX4

Xiao-Jun Lu1, Wen-Wen Gao2, Jia-Cheng Li1

  • 1Department of Urology, Shanghai FourthPeople's Hospital, School of Medicine, Tongji University, Shanghai, 200434, China.

Biochemistry and Biophysics Reports
|November 15, 2023
PubMed

Insights

MicroRNA-381 (miR-381) suppresses renal cell tumorigenesis by targeting SOX4 in cancer stem cells (CSCs). Restoring miR-381 may predict Sunitinib treatment benefits in renal cell carcinoma (RCC) patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Cancer stem cells (CSCs) drive tumor development and recurrence.
  • MicroRNAs (miRNAs) are key regulators of CSC stemness.
  • Renal cell carcinoma (RCC) pathogenesis involves CSCs, but regulatory mechanisms are not fully understood.

Purpose of the Study:

  • To investigate the role of miR-381 in renal cell CSCs and tumorigenesis.
  • To elucidate the molecular mechanism of miR-381 action.
  • To evaluate miR-381 as a potential biomarker for Sunitinib efficacy in RCC.

Main Methods:

  • Analysis of miR-381 levels in renal cell CSCs.
  • Functional assays to assess the impact of miR-381 modulation on tumorigenesis and CSC properties.
  • Mechanism studies involving SOX4 interaction and gene expression analysis.
  • Validation in patient-derived xenografts (PDX) and clinical patient cohorts.

Main Results:

  • Renal cell CSCs exhibit suppressed miR-381 levels.
  • miR-381 overexpression inhibits renal cell tumorigenesis and CSC-like properties by downregulating SOX4.
  • Low miR-381 levels correlate with SOX4 upregulation.
  • miR-381 levels can predict response to Sunitinib treatment in RCC patients, and SOX4 can reverse this sensitivity.

Conclusions:

  • miR-381 plays a critical role in regulating renal cell CSC-like properties and tumorigenesis.
  • The miR-381/SOX4 axis is a key mechanism in RCC development.
  • miR-381 is a promising therapeutic target and predictive biomarker for Sunitinib therapy in RCC.
Keywords:
Cancer stem cellRenal cell carcinomaSOX4SunitinibmiR-381

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