The inhibitory effect of KIAA1456 on the proliferation and metastasis of epithelial ovarian cancer through SSX1 and AKT signaling pathway

作者全名："Zhang, Yingfeng; Sun, Congcong; Gao, Yanhong; Mao, Yanhua; Wu, Benyuan; Li, Changjiang; Zhang, Wenwen; Wang, Jia"

作者地址："[Zhang, Yingfeng; Sun, Congcong; Mao, Yanhua; Wu, Benyuan; Li, Changjiang; Zhang, Wenwen; Wang, Jia] Chongqing Med Univ, Univ Town Hosp, Chongqing 401331, Peoples R China; [Gao, Yanhong] Fuling Cent Hosp Chongqing, Chongqing 400000, Peoples R China"

通信作者："Wang, J (通讯作者)，Chongqing Med Univ, Univ Town Hosp, Chongqing 401331, Peoples R China."

来源：JOURNAL OF CANCER

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000976572900004

JCR分区：Q2

影响因子：3.3

年份：2023

卷号：14

期号：5

开始页：770

结束页：783

文献类型：Article

关键词：Akt signaling pathway; epithelial ovarian cancer; KIAA1456; SSX1; proliferation

摘要："Background: KIAA1456 is effective in the inhibition of tumorigenesis. We previously confirmed that KIAA1456 inhibits cell proliferation and metastasis in epithelial ovarian cancer (EOC). In the current study, the specific molecular mechanisms and clinical significance of KIAA1456 underlying the repression of EOC were investigated.Methods: Immunohistochemistry was used to evaluate the protein expression of KIAA1456 and SSX1 in EOC and normal ovarian tissues. The relationship of KIAA1456 and SSX1 with overall survival of patients with EOC was analysed with Kaplan-Meier survival curve and log-rank tests. KIAA1456 was overexpressed and silenced in HO8910PM cells with lentivirus. Anticancer activities of KIAA1456 was tested by CCK8, plate clone formation assay, flow cytometry, wound healing assay and Transwell invasion assay. Xenograft tumour models were used to investigate the effects of KIAA1456 on tumour growth in vivo. Bioinformatics analyses of microarray profiling indicated that SSX1 and the PI3K/AKT were differentially expressed in KIAA1456-overexpressing and control cells. The downstream factors of PI3K/AKT that are related to cell growth and apoptosis.Results: KIAA1456 expression was lower in EOC than in normal ovarian tissues. Its expression negatively correlated with pathological grade. Pearson's correlation analysis showed that KIAA1456 negatively correlated with SSX1 expression. The overexpression of KIAA1456 in HO8910PM cells inhibited proliferation, migration and invasion and promoted apoptosis. The silencing of KIAA1456 resulted in the opposite behaviour. A xenograft tumour experiment showed that KIAA1456 overexpression inhibited tumour growth in vivo. The overexpression of KIAA1456 inhibited SSX1 and AKT phosphorylation in HO8910PM cells, causing the inactivation of the AKT pathway and eventually reducing the expression of PCNA, CyclinD1, MMP9 and Bcl2. The silencing of KIAA1456 resulted in the opposite behaviour. SSX1 overexpression could partially reverse the KIAA1456-induced biological effect.Conclusion: KIAA1456 may serve as a tumour suppressor via the inactivation of SSX1 and the AKT pathway, providing a promising therapeutic target for EOC."

基金机构："basic and cutting-edge research projects in Yuzhong District, Chongqing [20180153]; project of Chongqing Science and Technology Commission [cstc2018jcyjAX0809]; project of Science and Technology Research Project of Chongqing Education Commission [KJQN202200462]"

基金资助正文："This work was funded by the basic and cutting-edge research projects in Yuzhong District, Chongqing, 20180153, study on the mechanism of suppressor gene KIAA1456 regulating epithelial ovarian cancer through SSX1. This work was also funded by project of Chongqing Science and Technology Commission, cstc2018jcyjAX0809, the ananlysis of human tRNA methyltansferase 9-like regulating the proliferation and invasion of epithelial ovarian cancer cell. This work was also funded by project of Science and Technology Research Project of Chongqing Education Commission, KJQN202200462, study on the effect and mechanism of LncRNA RMST and Notch signaling pathway on trophoblast cells."