The RNA-Binding Protein RBPMS1 Inhibits Breast Cancer Stem Cell Properties By Repression Of Sox2

Objective:Breast cancer stem cells (BCSCs) are a small subpopulation of stem-like cells or tumor-initiating cells having the ability to develop or differentiate into a spectrum of more mature progenies. RBPMS 1 is a member of RNA-binding proteins and plays a role in breast cancer cell proliferation and migration however its role in breast cancer stem cell (BCSCs) remains unclear. This paper mainly studies the molecular mechanism of RBPMS 1 in the regulation of breast cancer stem cells, clarify the role of RBPMS 1 in breast cancer stem cell self-renewal and drug resistance, clear expression and clinical significance of RBPMS 1 in breast cancer specimens. To provide new ideas for the diagnosis and treatment of breast cancer.Methods:1 The effect of RBPMS 1 on breast cancer stem cells:detection of CD44+/CD24-/low and ALDH+cells by flow cytometry; the number and the size of tumor microspheres were detected after suspension culture.2 The regulation of RBPMS 1 on the growth of breast cancer:we use the growth curve to detect the influence of RBPMS 1 on the growth rate of breast cancer; we utilizethe scratch test to detect the effect of RBPMS 1 on the migration of breast cancer.3 The mechanism of RBPMS 1 regulating breast cancer stem cells and drug resistance:we use Western blot to analysis the regulation of RBPMS 1 on breast cancer stem cellsrelated transcription factors; through drug resistance to test whether RBPMS 1 regulate the drug resistance in breast cancer cell lines by Sox2.4 clinical significance:the expression of RBPMS 1 in breast cancer tissues and adjacent tissues was detected by immunohistochemistry and the difference between the adjacent tissues and the adjacent tissues was compared.Result:We report here a significant upregulation of BCSCs in both MCF-7 and T47D cells when downregulation the expression of RBPMS1. After knockdown the expression of RBPMS1, the proportion of CD44+/CD24-/low cells and ALDH+cells was increased, overexpression of three isforms of RBPMS1 in RBPMS1 shRNA-transfected breast cancer cells can effectively inhibit the upregulation of breast cancer stem cells. Knockdown the expression of RBPMS1 also improved the ability of mammosphere formation and grug resistance. Western blot analysis showed an apparent increase of Sox2 in RBPMS1 shRNA cells. Consistently the function of RBPMS1 siRNA can be inhibited by reducing Sox2 expression. Moreover we find a significant upregulation of Sox2 and downregulation of RBPMS1 propagated as suspension spheres in vitro.Conclusion:The expression of RBPMS1 in breast cancer tissue is reduced. And we provide evidence that RBPMS1 plays an important role in BCSCs and grug resistance by repression of Sox2.