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中华临床医师杂志(电子版) ›› 2020, Vol. 14 ›› Issue (03) : 232 -237. doi: 10.3877/cma.j.issn.1674-0785.2020.03.016

所属专题: 文献

基础研究

YWHAZ在皮肤黑色素瘤中的临床及生物学意义
代杰1, 周琳1, 孔燕1, 郭军1, 斯璐1,()   
  1. 1. 100142 北京大学肿瘤医院暨北京市肿瘤防治研究所肾癌黑色素瘤内科,恶性肿瘤发病机制及转化研究教育部重点实验室
  • 收稿日期:2020-01-21 出版日期:2020-03-15
  • 通信作者: 斯璐
  • 基金资助:
    北京市自然科学基金资助项目(7202024); 北京市优秀人才培养资助项目(2016000021223ZK18); 国家自然科学基金资助项目(81972566, 81972562)

Clinical and biological significance of YWHAZ in cutaneous melanoma

Jie Dai1, Lin Zhou1, Yan Kong1, Jun Guo1, Lu Si1,()   

  1. 1. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute, Beijing 100142, China
  • Received:2020-01-21 Published:2020-03-15
  • Corresponding author: Lu Si
  • About author:
    Corresponding author: Si Lu, Email:
引用本文:

代杰, 周琳, 孔燕, 郭军, 斯璐. YWHAZ在皮肤黑色素瘤中的临床及生物学意义[J]. 中华临床医师杂志(电子版), 2020, 14(03): 232-237.

Jie Dai, Lin Zhou, Yan Kong, Jun Guo, Lu Si. Clinical and biological significance of YWHAZ in cutaneous melanoma[J]. Chinese Journal of Clinicians(Electronic Edition), 2020, 14(03): 232-237.

目的

探讨YWHAZ在皮肤黑色素瘤中的表达及其临床意义,初步检测YWHAZ在皮肤黑色素瘤中的生物学功能。

方法

使用GEO数据库分析YWHAZ在皮肤黑色素瘤与良性痣间的表达差异,使用TCGA皮肤黑色素瘤数据集分析YWHAZ表达与皮肤黑色素瘤患者总生存之间的相关性。通过体外实验,敲减YWHAZ在皮肤黑色素瘤细胞中的表达,CCK8法检测细胞增殖,流式检测细胞凋亡,Transwell实验检测细胞迁移及侵袭能力改变。

结果

黑色素瘤组织中YWHAZ的平均相对表达量5.785±0.128,明显高于良性痣中YWHAZ的平均相对表达量(4.704±0.281),差异有统计学意义(t=4.023,P=0.0002);YWHAZ高表达组中位生存期(47.28个月)较低表达组(89.13个月)明显缩短(P=0.0085)。体外实验结果显示YWHAZ敲减后黑色素瘤细胞增殖减慢、凋亡细胞比例增加、迁移及侵袭能力减弱。

结论

YWHAZ在皮肤黑色素瘤中发挥癌基因的作用,降低YWHAZ表达水平可抑制黑色素瘤的恶性表型。

Objective

The aim of the study was to analyze the expression of YWHAZ in cutaneous melanoma, and to evaluate its association with survival of melanoma patients and biological function.

Methods

The GEO database was used to explore the difference in YWHAZ expression between cutaneous melanoma and benign melanocytic nevi. TCGA database was used to analyze the correlation between YWHAZ expression and melanoma prognosis. The biological function of YWHAZ was investigated in vitro through gene knockdown using siRNA against YWHAZ. Cell proliferation was detected by CCK8 assay, cell apoptosis was analyzed by flow cytometry, and cell migration and invasion abilities were evaluated by Transwell assay.

Results

According to the GEO dataset GSE3189, we found that YWHAZ was highly expressed in cutaneous melanoma tissues (5.785±0.128) compared to benign melanocytic nevi [(4.704±0.281), t=4.023, P=0.0002]. The TCGA cutaneous melanoma data showed that high YWHAZ expression was associated with a shorter overall survival. Loss-of-function studies demonstrated that YWHAZ knockdown could inhibit melanoma cell proliferation, migration, and invasion, and promote cell apoptosis.

Conclusion

YWHAZ is overexpressed in cutaneous melanoma and associates with a shorter overall survival. Increased expression of YWHAZ can promote the malignant biological behavior of melanoma cells.

图1 YWHAZ表达水平与皮肤黑色素瘤患者总生存相关
图2 敲减YWHAZ黑色素瘤细胞模型构建 图a为Western blot检测M21细胞株YWHAZ敲减后YWHAZ蛋白相对表达;图b为荧光定量RT-PCR检测M21细胞株YWHAZ敲减后YWHAZ的mRNA相对表达量;与siCTRL的mRNA相对表达量比较,**P<0.01,****P<0.0001
图3 敲减YWHAZ后M21细胞的增殖曲线,分别转染siYWHAZ#1,siYWHAZ#2,siYWHAZ#3三条不同的siRNA对YWHAZ进行敲减,siCTRL为阴性对照组,与siCTRL比较,***P<0.001,****P<0.0001
图4 敲减YWHAZ对黑色素瘤细胞凋亡的影响siCTRL为阴性对照组,siYWHAZ为YWHAZ敲减组,图a为流式图,图b为柱形图,****P<0.0001
图5 敲减YWHAZ对黑色素瘤细胞迁移及侵袭能力的影响 图a为Transwell迁移实验检测敲减YWHAZ后M21迁移能力的改变;图b为Transwell侵袭实验检测敲减YWHAZ后M21侵袭能力的改变;siCTRL为阴性对照组,siYWHAZ为YWHAZ敲减组;染色方法均为1%结晶紫染色,放大倍数100;****P<0.0001
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