4.7 Article

RBMS2 Chemosensitizes Breast Cancer Cells to Doxorubicin by Regulating BMF Expression

期刊

INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
卷 18, 期 4, 页码 1724-1736

出版社

IVYSPRING INT PUBL
DOI: 10.7150/ijbs.66480

关键词

RBMS2; BMF; apoptosis; chemosensitization; doxorubicin; breast cancer

资金

  1. National Natural Science Foundation of China [81972486, 81802644, 81802748]
  2. Key Medical Talents of Jiangsu Province [ZDRCA2016029]
  3. 333 High-level Talents Training Project of Jiangsu Province [BRA2016505]
  4. International Cooperation Project of Jiangsu Provincial Science and Technology Department [BZ2018054]
  5. Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) [JX10231801]

向作者/读者索取更多资源

Chemoresistance, which is closely associated with therapeutic outcomes and prognosis in breast cancer patients, has been shown to be influenced by RNA binding proteins (RBPs) such as RBMS2. In this study, the researchers found that upregulation of RBMS2 enhanced sensitivity to doxorubicin and induced apoptosis in breast cancer cells. Furthermore, the chemosensitizing effect of RBMS2 was found to be mediated by the regulation of the Bcl-2 modifying factor (BMF). These findings suggest that RBMS2 may serve as a potential therapeutic target for drug-resistant breast cancer.
Chemoresistance is closely related to the therapeutic effect and prognosis in breast cancer patients. Increasing evidences demonstrated that RNA binding proteins (RBPs) have notable roles in regulating cancer cell proliferation, metastasis and chemotherapeutic sensitivity. RNA binding motif single stranded interacting protein 2 (RBMS2), an RBP, has been considered to be a tumor suppressor in several cancers. However, its role of doxorubicin sensitivity in breast cancer patients has not yet been fully revealed. Here, we performed doxorubicin cytotoxicity assay, flow cytometry and mouse xenograft model to examine the influence of RBMS2 on doxorubicin sensitization in vitro and in vivo. RIP assay and dual-luciferase reporter assay were performed to explore the relationship between RBMS2 and BMF. Our data demonstrated that upregulation of RBMS2 in breast cancer cells could enhance sensitivity to doxorubicin and promote apoptosis in the presence of doxorubicin, while inhibition of RBMS2 showed an opposite trend. Moreover, this chemosensitizing effect of RBMS2 could be reversed by the inhibition of Bcl-2 modifying factor (BMF). RBMS2 positively regulated BMF expression and increased BMF-induced expression of (cleaved) caspase 3, (cleaved) caspase 9 and poly (ADP-Ribose) polymerase (PARP). These results uncovered a novel mechanism for RBMS2 in the sensibilization of doxorubicin, suggesting that RBMS2 may act as a potential therapeutic target for drug-resistant breast cancer.

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