Abstract：Objective: To investigate the effect of down-regulation of SIP1 on apoptosis, migration and invasion of endometrial cancer cells and its mechanism. Methods: Human endometrial carcinoma cell line HEC-1A was divided into control group, NC group, SIP1 down-regulated group (transfected with si-SIP1), Y27632 group (ROCK inhibitor), SIP1 down-regulated group+Y27632 group (transfected with si-SIP1+ROCK inhibitor). The apoptosis, migration ability and invasion ability of each group were detected by flow cytometry and Transwell assay. The expression levels of apoptosis key protein b-lymphoma-2 gene (Bcl-2), apoptosis gene Bcl-2 related protein X (Bax), caspase family protein 3 (caspase 3), Rho related kinase 2 (ROCK-2) and Moesin were detected by Western blot. Twenty SPF-grade BALB/c mice were tumor-loaded subcutaneously to establish an endometrial cancer tumor model. The control group (n=10) was tumor-loaded with human endometrial cancer HEC-1A cells, and the SIP1 down-regulated group (n=10) was tumor-loaded with human endometrial cancer HEC-1A cells with down-regulated SIP1. Tumor volume was measured with vernier caliper every 3 days, and the tumor growth curve was drawn for 21 days. At the end point, the tumor mass of each mouse was measured and the expression levels of ROCK-2 and Moesin protein in tumor tissues were detected. Results: The results of cell experiment showed that compared with the control group and NC group, the proportion of apoptosis, the number of cell migration and cell invasion in SIP1 down regulation group, Y27632 group and SIP1 down regulation + Y27632 group increased significantly (P<0.01), there was no significant difference between NC group and control group (P>0.05). The results of Western blot showed that the expression levels of ROCK-2 and Moesin in SIP1 down regulated group, Y27632 group and SIP1 down regulated + Y27632 group decreased compared with the control group and NC group (P<0.01). The mice experiment revealed that compared with the control group, the tumor volume, tumor mass and the expression levels of ROCK-2 and Moesin in tumor tissues decreased significantly after down-regulation of SIP1 (P<0.01). Conclusion: Down regulation of SIP1 can promote apoptosis, inhibit migration and invasion of human endometrial cancer cell line HEC-1A, and its may be related to the regulation of ROCK-2/Moesin signal pathway.
刘雪洁, 李晓妍, 张凤. 基于ROCK-2/Moesin信号通路探究下调SIP1对子宫内膜癌细胞凋亡侵袭迁移的影响[J]. 河北医学, 2023, 29(3): 364-369.
LIU Xuejie, LI Xiaoyan, et al. Effects of Downregulation of SIP1 on Apoptosis Invasion and Migration of Endometrial Cancer Cells Based on ROCK-2/Moesin Signaling Pathway. HeBei Med, 2023, 29(3): 364-369.
[1] Keiichiro Nakamura,Atsushi Hongo,Junichi Kodama,et al.The role of hepatocyte growth factor activator inhibitor (HAI)-1 and HAI-2 in endometrial cancer[J].Int Cancer,2011,128(11):2613-2624. [2] Yuanyuan Ye,Jun Yang,Qin Hu,et al SIP1 serves a role in HBx-induced liver cancer growth and metastasis[J].Int Oncol,2019,55(5):1019-1032. [3] Quentin Lubart,Helene Vitet,Fabien Dalonneau,et al.Role of phosphorylation in moesin interactions with phosphatidylinositol-4,5-bis(phosphate)-containing biomimetic membranes:a biophysical study[J].Biophys,2018,114(1):98-112. [4] Ephraim A,Ansa-Addo,Yongliang Zhang,et al.Sirtuin,et al.Membrane-organizing protein moesin controls treg differentiation and antitumor immunity via TGF-β signaling[J].Clin Invest,2017,27(4):1321-1337. [5] Lili Li,Jiangtao Fan,Dahai Li,et,al.Influence of YKL-40 gene RNA interference on the biological behaviors of endometrial cancer HEC-1A cells[J].Oncol Lett,2018,16(2):1777-1784. [6] 魏旭静,李林,张红真,等.多西环素对荷瘤小鼠子宫内膜癌组织中CCAT1、MMP-2及TIMP-2表达的影响[J].中国免疫学杂志,2020,36(21):2619-2623 [7] Hui Yang,Rui Yang,Hao Liu,et al.Knockdown of peroxisome proliferator-activated receptor gamma coactivator-1 alpha increased apoptosis of human endometrial cancer HEC-1A cells[J].Onco Targets Ther,2016,24(9):5329-5338. [8] Xuren Sun,Zhe Sun,Zhi Zhu,et al.Expression of SIP1 is strongly correlated with LDHA and shows a significantly poor outcome in gastric cancer[J].Tumour Biol,2015,36(10):7521-7530. [9] Anusha Sathyanarayanan,microRNA-145 modulates epithelial-mesenchymal transition and suppresses proliferation,migration and invasion by targeting SIP1 in human cervical cancer cells[J].Cell Oncol (Dordr),2017,40(2):119-131. [10] Song Hu,Xiaoxing Shi,Yi wen Liu,et al.CD44 cross-linking increases malignancy of breast cancer via upregulation of p-Moesin[J].Cancer Cell Int,2020,20(1):563. [11] Lifeng Yu,Lin Zhao,Huizhe Wu,et al.Moesin is an independent prognostic marker for ER-positive breast cancer[J].Oncol Lett,2019,17(2):1921-1933.
2023, Vol. 29 
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