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CBFA2T2与肾细胞癌中的癌症干细胞状态相关。

CBFA2T2 is associated with a cancer stem cell state in renal cell carcinoma.

作者信息

Chen Du-Chu, Liang You-De, Peng Liang, Wang Yi-Ze, Ai Chun-Zhi, Zhu Xin-Xing, Yan Ya-Wei, Saeed Yasmeen, Yu Bin, Huang Jingying, Gao Yuxin, Liu Jiaqi, Jiang Yi-Zhou, Liu Min, Chen Demeng

机构信息

State Key Laboratory of Stress Cell Biology, School of Life Sciences, Xiamen University, Xiamen, 361005 Fujian China.

Department of Oncology, Chinese PLA General Hospital, Beijing, 100853 China.

出版信息

Cancer Cell Int. 2017 Nov 14;17:103. doi: 10.1186/s12935-017-0473-z. eCollection 2017.

Abstract

BACKGROUND

Renal cell carcinoma (RCC) is the most common kidney cancer, accounting for approximately 80-90% of all primary kidney cancer. Treatment for patients with advanced RCC remains unsatisfactory. Rare cancer stem cells (CSCs) are proposed to be responsible for failure of current treatment.

METHODS

OncoLnc was used as a tool for interactively exploring survival correlations. Gene manipulation and expression analysis were carried out using siRNA, RT-PCR and Western blotting. Wound healing and invasion assays were used for phenotypical characterization. Aldefluor assay and FACS sorting Sphere culture were used to determine the "stemness" of CSCs. Co-Immunoprecipitation (Co-IP) was used to examine the interaction between OCT4 and CBFA2T2. Student's t-test and Chi square test was used to analyze statistical significance.

RESULTS

CBFA2T2 expression can significantly predict the survival of RCC patients. Knocking-down of CBFA2T2 can inhibit cell migration and invasion in RCC cells in vitro, and reduce ALDH CSCs populations. CBFA2T2 expression is necessary for sphere-forming ability and cancer stem cells marker expression in RCC cell lines.

CONCLUSIONS

Our data suggest that CBFA2T2 expression correlates with aggressive characteristics of RCC and CBFA2T2 is required for maintenance of "stemness" through regulation of stem cells factors, thereby highlighting CBFA2T2 as a potential therapeutic target for RCC treatment.

摘要

背景

肾细胞癌(RCC)是最常见的肾癌,约占所有原发性肾癌的80 - 90%。晚期RCC患者的治疗效果仍不尽人意。有研究提出,罕见的癌症干细胞(CSCs)是导致当前治疗失败的原因。

方法

使用OncoLnc作为交互式探索生存相关性的工具。采用小干扰RNA(siRNA)、逆转录-聚合酶链反应(RT-PCR)和蛋白质免疫印迹法进行基因操作和表达分析。使用伤口愈合和侵袭试验进行表型特征分析。采用醛脱氢酶(Aldefluor)检测法和荧光激活细胞分选(FACS)球形培养法来确定CSCs的“干性”。采用免疫共沉淀法(Co-IP)检测八聚体结合转录因子4(OCT4)与CBFA2T2之间的相互作用。采用学生t检验和卡方检验分析统计学意义。

结果

CBFA2T2表达可显著预测RCC患者的生存率。敲低CBFA2T2可在体外抑制RCC细胞的迁移和侵袭,并减少醛脱氢酶阳性CSCs群体。CBFA2T2表达对于RCC细胞系的成球能力和癌症干细胞标志物表达是必需的。

结论

我们的数据表明,CBFA2T2表达与RCC的侵袭性特征相关,并且CBFA2T2通过调节干细胞因子来维持“干性”是必需的,从而突出了CBFA2T2作为RCC治疗潜在靶点的地位。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8445/5686942/ce039c7226ec/12935_2017_473_Fig1_HTML.jpg

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