TIM-3 gene is highly expressed in ephithelial ovarian cancer to promote proliferation and migration of ovarian cancer cells.
10.12122/j.issn.1673-4254.2022.02.04
- Author:
Ye Lin HUO
1
;
Yue WANG
2
;
Na AN
2
;
Xue DU
1
Author Information
1. Department of Gynecology, General Hospital of Tianjin Medical University, Tianjin 300000, China.
2. Department of Oncology, Affiliated Hospital of Hebei University, Baoding 071000, China.
- Publication Type:Journal Article
- Keywords:
GEPIA database;
TIM-3 gene;
Wnt/β-catenin signaling pathway;
biological behaviors;
epithelial ovarian cancer
- MeSH:
Carcinoma, Ovarian Epithelial/pathology*;
Cell Line, Tumor;
Cell Movement/genetics*;
Cell Proliferation/genetics*;
Female;
Gene Expression Regulation, Neoplastic;
Hepatitis A Virus Cellular Receptor 2/metabolism*;
Humans;
Ovarian Neoplasms/metabolism*
- From:
Journal of Southern Medical University
2022;42(2):190-200
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To analyze the expression of immunoglobulin mucin molecule 3 (TIM-3) in epithelial ovarian cancer (EOC) and the effects of TIM-3 knockdown and overexpression on proliferation and migration of ovarian cancer cells.
METHODS:We analyzed TIM-3 expression in EOC and normal ovarian tissues using GEPIA database. We also detected TIM-3 expression levels in 82 surgical specimens of EOC and 18 specimens of normal ovarian tissues using immunohistochemistry, and analyzed the correlation of TIM-3 expression with clinicopathological parameters and survival outcomes of the patients. The expression of TIM-3 and Wnt1 mRNA in the tissues were detected using qRT-PCR. We constructed SKOV3 cell models of TIM-3 knockdown and overexpression and examined the changes in proliferation, apoptosis, migration and invasion of the cells using MTT assay, Annexin V-FITC/PI staining, scratch test and Transwell assay. The activity of Wnt/β-catenin pathway in the transfected was detected using dual luciferase reporter assay, and the mRNA levels of TCF-7, TCCFL-2 and CD44 were detected using qPCR. The protein expressions of MMP-9, CD44, Wnt1, β-catenin and E-cad in the transfected cells were detected with Western blotting.
RESULTS:The positive expression rate of TIM-3 was significantly higher in EOC tissues than in normal ovarian tissues (P < 0.05). The expression of TIM-3 was significantly correlated with FIGO stage, histological differentiation and lymph node metastasis, and was positively correlated with Wnt1 level (P < 0.05). In SKOV3 cells, TIM-3 knockdown significantly lowered the activity of Wnt/ β-catenin pathway, inhibited cell proliferation, migration and invasion, and promoted cell apoptosis. TIM-3 knockdown significantly down-regulated the mRNA levels of TCF-7, TCFL-2 and CD44 and the protein levels of MMP-9, CD44, Wnt1 and β-catenin, and significantly up-regulated the expression level of E-cad (P < 0.05). Overexpression of TIM-3 caused opposite effects in SKOV3 cells.
CONCLUSION:TIM-3 is highly expressed in EOC tissue to promote malignant behaviors of the tumor cells possibly by activating the Wnt/β-catenin signal pathway.
