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

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 resistan...

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Bibliographic Details
Published in:Apoptosis (London) 2023-02, Vol.28 (1-2), p.233-246
Main Authors: Wang, Yang, Zhang, Lin, Sun, Xiao-Lin, Lu, Ya-Chun, Chen, Si, Pei, Dong-Sheng, Zhang, Lan-Sheng
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Apoptosis - radiation effects
Bcl-2 protein
Biochemistry
Biomedical and Life Sciences
Biomedicine
Breast cancer
Breast Neoplasms - pathology
Cancer Research
Cell Biology
Cell Cycle Proteins - metabolism
Cell Line, Tumor
Disease Models, Animal
Ethylenediaminetetraacetic acid
Female
Flow cytometry
Glycoproteins
Humans
Immunofluorescence
Messenger RNA
Methylation
Methyltransferase
Methyltransferases
mRNA
N6-methyladenosine
Oncology
Radiation therapy
Radiation tolerance
Radioresistance
Radiotherapy
RNA Splicing Factors - metabolism
RNA, Messenger - metabolism
RNA, Small Interfering - genetics
siRNA
Stem cells
Therapeutic targets
Tumor cells
Tumors
Virology
Xenografts
Xenotransplantation
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Summary: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.
ISSN:1360-8185
1573-675X
DOI:10.1007/s10495-022-01784-3