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SURF4 maintains stem-like properties via BIRC3 in ovarian cancer cells
Yongfang Yue,Lili Xia,Shanshan Xu,Conghui Wang,Xinyu Wang,Weiguo Lu,Xing Xie 대한부인종양학회 2020 Journal of Gynecologic Oncology Vol.31 No.4
Objective: As cancer stem cells (CSCs) are considered as the origin of tumor development,recurrence, and drug resistance, we aimed to explore the mechanism related to modulatingstemness in CSCs, thus facilitating to search for new therapeutic strategy for ovarian cancer. Methods: In this study, ovarian cancer stem cells (OCSCs) induced from cell line 3AOand A2780 were enriched in serum-free medium (SFM). The effect of SURF4 on CSC-likeproperties was evaluated by sphere-forming assays, re-differentiation assays, quantitativereal-time polymerase chain reaction, flow cytometry, Western blotting, cell viability assaysand in vivo xenograft experiments. The downstream molecule participating in SURF4maintaining stemness was screened by RNA-sequencing and identified by the experiments ofgene function. Results: SURF4 was upregulated expressed in OCSCs. Knockdown of SURF4 reduced theexpression of the related stem markers (SOX2 and c-MYC), inhibited self-renewal ability,and improved the sensitivity to chemotherapeutic drugs (paclitaxel and cisplatin) in OCSCs. SURF4 knockdown also inhibited tumorigenesis in nonobese diabetic/severe combinedimmunodeficiency mice. BIRC3 expression was controlled by SURF4, and BIRC3 showedthe similar effect as SURF4 did, and BIRC3 overexpression partially recovered stem-likeproperties abolished by SURF4 knockdown. Conclusion: Our findings suggest that SURF4 possesses the ability to maintain stemness ofOCSCs via BIRC3, and may serve as a potential target in stem cell-targeted therapy forovarian cancer.