Abstract
PurposeEvidence describing TMED3 in the context of breast cancer is scarce, and the effect of TMED3 on Wnt/β-catenin signaling in breast cancer has not been reported. The objective of this study was to determine the potential physiological functions and molecular mechanisms of TMED3 in breast cancer.Materials and MethodsQuantitative real-time PCR and Western blot analysis were used to analyze the expression of TMED3 mRNA and protein in 182 paraffin-embedded primary breast cancer tissues and 60 paired noncancerous tissues and 25 fresh primary breast cancer tissues and surrounding adjacent noncancerous tissues. Associations between TMED3 expression and clinicopathologic factors or overall survival were determined. The effects of overexpression or knockdown of TMED3 on proliferation, migration, invasion, and cell cycle progression in breast cancer cell lines were investigated with the Cell Counting Kit-8, clone formation assay, transwell assay, wound healing assay, and flow cytometry, respectively. Immunofluorescence and Western blot analysis were used to detect the expression of cell cycle, migration-related, and Wnt/β-catenin signaling proteins.ResultsThe expression of TMED3 mRNA and protein were significantly increased in breast cancer tissues and cell lines compared to normal controls. TMED3 upregulation was significantly correlated with clinicopathologic characteristics and predicted poor prognosis in patients with breast cancer. TMED3 overexpression promoted proliferation, migration, invasion, and cell cycle progression compared to controls in breast cancer cell lines. TMED3 knockdown suppressed proliferation, migration, invasion, and cell cycle progression compared to controls in breast cancer cell lines. TMED3 promoted proliferation and migration of breast cancer cells by a mechanism that involved Wnt/β-catenin signaling.ConclusionTMED3 behaves as an oncogene that promotes the proliferation and migration of breast cancer cells by a mechanism that involved Wnt/β-catenin signaling. Strategies targeting TMED3 have potential therapeutic implications for patients with breast cancer.
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