SURF4 maintains stem-like properties via BIRC3 in ovarian cancer cells
SURF4 maintains stem-like properties via BIRC3 in ovarian cancer cells
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SURF4 通过 BIRC3 在卵巢癌细胞中维持干细胞样特性
DOI：
10.3802/jgo.2020.31.e46
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发表时间：
2020-01
影响因子：
3.9
通讯作者：
Xie Xing
中科院分区：
文献类型：
--
作者：
Yue Yongfang;Xia Lili;Xu Shanshan;Wang Conghui;Wang Xinyu;Lu Weiguo;Xie Xing
目的鉴于肿瘤干细胞(CSCs)是肿瘤发生、复发和耐药的重要来源，本研究旨在探讨CSCs调节干细胞干性的相关机制，为卵巢癌的治疗提供新的思路。方法用无血清培养法(SFM)富集卵巢癌干细胞(OCSCs)。通过球体形成法、再分化实验、实时定量聚合酶链式反应、流式细胞术、Western blotting、细胞存活率测定和体内移植实验评价SURF4对CSC样特性的影响。通过RNA测序筛选出参与SURF4保持茎性的下游分子，并通过基因功能实验对其进行鉴定。结果SURF4在口腔鳞状细胞癌中表达上调。SURF4基因敲除后，OCSCs中相关干细胞标志物SOX2和c-myc的表达减少，自我更新能力受到抑制，对化疗药物紫杉醇和顺铂的敏感性增强。SURF4基因敲除也抑制了非肥胖糖尿病/严重联合免疫缺陷小鼠的肿瘤形成。BIRC3的表达受SURF4的调控，BIRC3的表达与SURF4的作用相似，BIRC3的过表达部分恢复了被SURF4基因敲除的干细胞特性。结论SURF4具有通过BIRC3途径维持OCSCs干性的能力，有望成为卵巢癌干细胞靶向治疗的潜在靶点。
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 modulating stemness 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 3AO and A2780 were enriched in serum-free medium (SFM). The effect of SURF4 on CSC-like properties was evaluated by sphere-forming assays, re-differentiation assays, quantitative real-time polymerase chain reaction, flow cytometry, Western blotting, cell viability assays and in vivo xenograft experiments. The downstream molecule participating in SURF4 maintaining stemness was screened by RNA-sequencing and identified by the experiments of gene function. Results SURF4 was upregulated expressed in OCSCs. Knockdown of SURF4 reduced the expression 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 combined immunodeficiency mice. BIRC3 expression was controlled by SURF4, and BIRC3 showed the similar effect as SURF4 did, and BIRC3 overexpression partially recovered stem-like properties abolished by SURF4 knockdown. Conclusion Our findings suggest that SURF4 possesses the ability to maintain stemness of OCSCs via BIRC3, and may serve as a potential target in stem cell-targeted therapy for ovarian cancer.
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影响因子：
8.4
作者：
Monzani, Elena;Facchetti, Floriana;La Porta, Caterina A. M.
通讯作者：
La Porta, Caterina A. M.
影响因子：
7.7
作者：
Brian T. Emmer;G. Hesketh;E. Kotnik;Vi T. Tang;Paul J. Lascuna;Jie Xiang;A. Gingras;Xiao-Wei Chen-Xiao-Wei-C
通讯作者：
Brian T. Emmer;G. Hesketh;E. Kotnik;Vi T. Tang;Paul J. Lascuna;Jie Xiang;A. Gingras;Xiao-Wei Chen-Xiao-Wei-C
影响因子：
9.9
作者：
Wang J;Huo K;Ma L;Tang L;Li D;Huang X;Yuan Y;Li C;Wang W;Guan W;Chen H;Jin C;Wei J;Zhang W;Yang Y;Liu Q;Zhou Y;Zhang C;Wu Z;Xu W;Zhang Y;Liu T;Yu D;Zhang Y;Chen L;Zhu D;Zhong X;Kang L;Gan X;Yu X;Ma Q;Yan J;Zhou L;Liu Z;Zhu Y;Zhou T;He F;Yang X
通讯作者：
Yang X
DOI：
10.1016/j.bbrc.2018.05.116
发表时间：
2018-07-07
影响因子：
3.1
作者：
Kim, Jayoung;Hong, Chae Mi;Lee, Dongjun
通讯作者：
Lee, Dongjun
影响因子：
5.4
作者：
Lathia JD;Liu H
通讯作者：
Liu H