1. Academic Validation
  2. NRP1 contributes to stemness and potentiates radioresistance via WTAP-mediated m6A methylation of Bcl-2 mRNA in breast cancer

NRP1 contributes to stemness and potentiates radioresistance via WTAP-mediated m6A methylation of Bcl-2 mRNA in breast cancer

  • Apoptosis. 2022 Nov 4. doi: 10.1007/s10495-022-01784-3.
Yang Wang # 1 Lin Zhang # 1 Xiao-Lin Sun 1 Ya-Chun Lu 2 Si Chen 2 Dong-Sheng Pei 1 Lan-Sheng Zhang 3
Affiliations

Affiliations

  • 1 Department of Pathology, Xuzhou Medical University, Xuzhou, 221004, China.
  • 2 Department of Oncological Radiotherapy, The Second Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
  • 3 Department of Oncological Radiotherapy, The Second Affiliated Hospital of Xuzhou Medical University, Xuzhou, China. lanshengyan@163.com.
  • # Contributed equally.
Abstract

NRP1 is a transmembrane glycoprotein that is highly expressed in a variety of tumors. There is evidence that NRP1 can enhance the stem cell properties of tumor cells, which are thought to be resistant to radiotherapy. This study aims to elucidate the potential mechanism of NRP1 in radiation resistance. We transfected NRP1 siRNA and plasmid in breast Cancer cells to detect the expression of Cancer stem cell markers by western blot and qRT-PCR. The effect of NRP1 on radiotherapy resistance was assesses by immunofluorescence and flow cytometry. In vivo, we established xenograft tumor model treating with shRNA-NRP1 to assess radiotherapy sensitivity. We found that NRP1 could enhance the stem cell properties and confer radioresistance of breast Cancer cells. Mechanistically, we proved that NRP1 reduced IR-induced Apoptosis by downregulation of Bcl-2 via methyltransferase WTAP in m6A-depentent way. It is suggested that these molecules may be the therapeutic targets for improving the efficacy of radiotherapy for breast Cancer.

Keywords

Apoptosis; Breast cancer; NRP1; Radioresistance; m6A.

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