MYO3B 通过介导钙离子-RhoA/ROCK1 信号通路促进子宫内膜癌的进展。
MYO3B promotes cancer progression in endometrial cancer by mediating the calcium ion-RhoA/ROCK1 signaling pathway.
机构信息
Department of Gynecology, First Hospital of Shanxi Medical University, No.85, Jiefang South Road, Yingze District, Taiyuan, Shanxi Province, 030001, China.
Department of Basic Medicine, Shanxi Medical University, No.56, Xinjian South Road, Yingze District, Taiyuan, Shanxi Province, 030001, China.
出版信息
J Cancer Res Clin Oncol. 2024 Sep 19;150(9):424. doi: 10.1007/s00432-024-05940-x.
PURPOSE
This study aimed to investigate the effect of MYO3B on endometrial cancer (EC) proliferation and invasion.
METHODS
The expression of MYO3B in EC tissues and cells was analyzed using TCGA database, immunohistochemical staining, real-time PCR, and western blot (WB). Cell proliferation was detected by CCK8, Annexin V-APC/PI flow cytometry was used to detect apoptosis, intracellular calcium ion (Ca) was detected by flow cytometry with Fluo-4 AM fluorescent probe, cell migration by scratch assay, and cell invasion by Transwell assay, and the expression of proteins related to Ca homeostasis and RhoA/ROCK1 signaling pathway was detected by WB and immunofluorescence staining.
RESULTS
The expression of MYO3B was an influential factor in EC recurrence, and the expression of MYO3B was significantly up-regulated in EC tissues and cells, but down-regulated in KLE cells, and MYO3B knockdown inhibited the proliferation, migration, and invasion ability of EC cells and promoted apoptosis, suggesting that MYO3B plays a tumor-promoting role in EC. Furthermore, MYO3B knockdown decreased Ca concentration in EC cells and the RhoA/ROCK1 signaling pathway was inhibited, and the effect of MYO3B knockdown on RhoA/ROCK1 signaling was reversed by treatment with the Calmodulin agonist CALP-2, and the effects of MYO3B knockdown on cell proliferation, migration, and invasion were reversed after treatment with the RhoA agonist U-46,619.
CONCLUSION
MYO3B promotes the proliferation and migration of endometrial cancer cells via Ca-RhoA/ROCK1 signaling pathway. High expression of MYO3B may be a biomarker for EC metastasis.
目的
本研究旨在探讨 MYO3B 对子宫内膜癌（EC）增殖和侵袭的影响。
方法
使用 TCGA 数据库、免疫组织化学染色、实时 PCR 和 Western blot（WB）分析 MYO3B 在 EC 组织和细胞中的表达。通过 CCK8 检测细胞增殖，通过 Annexin V-APC/PI 流式细胞术检测细胞凋亡，通过 Fluo-4 AM 荧光探针流式细胞术检测细胞内钙离子（Ca），通过划痕实验检测细胞迁移，通过 Transwell 实验检测细胞侵袭，通过 WB 和免疫荧光染色检测与 Ca 稳态和 RhoA/ROCK1 信号通路相关的蛋白表达。
结果
MYO3B 的表达是 EC 复发的影响因素，MYO3B 在 EC 组织和细胞中的表达显著上调，而在 KLE 细胞中下调，MYO3B 敲低抑制 EC 细胞的增殖、迁移和侵袭能力并促进凋亡，表明 MYO3B 在 EC 中发挥促肿瘤作用。此外，MYO3B 敲低降低了 EC 细胞中的 Ca 浓度并抑制了 RhoA/ROCK1 信号通路，用钙调蛋白激动剂 CALP-2 处理可逆转 MYO3B 敲低对 RhoA/ROCK1 信号的影响，用 RhoA 激动剂 U-46,619 处理可逆转 MYO3B 敲低对细胞增殖、迁移和侵袭的影响。
结论
MYO3B 通过 Ca-RhoA/ROCK1 信号通路促进子宫内膜癌细胞的增殖和迁移。MYO3B 的高表达可能是 EC 转移的生物标志物。
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