EDARADD 沉默抑制膀胱癌细胞的增殖和迁移。

EDARADD silencing suppresses the proliferation and migration of bladder cancer cells.

机构信息

Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.

出版信息

Urol Oncol. 2022 Aug;40(8):382.e15-382.e24. doi: 10.1016/j.urolonc.2022.04.017. Epub 2022 May 28.

DOI:10.1016/j.urolonc.2022.04.017

PMID:35637063

Abstract

PURPOSE

Bladder cancer is a kind of common malignant cancer in the urinary system. The expression of EDARADD (ectodysplasin-A receptor-associated death domain) in bladder cancer is higher than the normal samples. However, its role in bladder cancer remains unknown. In the present study, we analyzed the expression of EDARADD in 81 bladder cancer samples by immunohistochemistry as well as its correlation with clinical characteristics. In addition, the role of EDARADD was also explored through loss of function.

MATERIALS AND METHODS

Cell proliferation assay and MTT assay were conducted to assess the proliferation of bladder cancer cells and transwell assay and wound healing assay were conducted to assess the migration of bladder cancer cells. On the other hand, the levels of epithelial-mesenchymal transition (EMT) associated proteins and the key molecules in the MAPK signaling pathway were detected by western blot. In vivo experiments were also conducted to determine the effect of EDARADD silencing on the metastasis of bladder cancer cells and the MAPK signaling pathway.

RESULTS

EDARADD was highly expressed in bladder cancer samples, especially in high-grade bladder cancer samples. The high EDARADD level indicated a poor survival. Interestingly, EDARADD silencing suppressed the proliferation, migration and EMT of bladder cancer cells. Furthermore, the MAPK signaling pathway was repressed by EDARADD silencing. Additionally, silencing EDARADD also inhibited the metastasis of bladder cancer and the MAPK signaling pathway in vivo. It is indicated that silencing EDARADD may suppress the proliferation and metastasis of bladder cancer cells through the MAPK signaling pathway.

CONCLUSION

These results indicate that EDARADD may become a probable target for the treatment of bladder cancer.

摘要

目的

膀胱癌是泌尿系统常见的恶性肿瘤之一。EDARADD（外胚层发育缺失受体相关死亡域）在膀胱癌中的表达高于正常样本。然而，其在膀胱癌中的作用尚不清楚。在本研究中，我们通过免疫组织化学分析了 81 例膀胱癌样本中 EDARADD 的表达及其与临床特征的相关性。此外，还通过功能丧失探索了 EDARADD 的作用。

材料和方法

通过细胞增殖试验和 MTT 试验评估膀胱癌细胞的增殖，通过 Transwell 试验和划痕愈合试验评估膀胱癌细胞的迁移。另一方面，通过 Western blot 检测上皮间质转化（EMT）相关蛋白和 MAPK 信号通路的关键分子的水平。还进行了体内实验，以确定 EDARADD 沉默对膀胱癌细胞转移和 MAPK 信号通路的影响。

结果

EDARADD 在膀胱癌样本中高度表达，尤其是在高级别膀胱癌样本中。高 EDARADD 水平表明预后不良。有趣的是，EDARADD 沉默抑制了膀胱癌细胞的增殖、迁移和 EMT。此外，EDARADD 沉默抑制了 MAPK 信号通路。此外，EDARADD 沉默还抑制了膀胱癌的转移和体内的 MAPK 信号通路。表明沉默 EDARADD 可能通过 MAPK 信号通路抑制膀胱癌细胞的增殖和转移。