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

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 expr ession 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 enh ance 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 impro ving the efficacy of radiotherapy for breast cancer.
Source: Apoptosis - Category: Molecular Biology Source Type: research