1. TMED2 Induces Cisplatin Resistance in Breast Cancer via Targeting the KEAP1-Nrf2 Pathway.
- Author
-
Liang C, Zhang HY, Wang YQ, Yang LA, Du YS, Luo Y, Zhang TC, and Xu Y
- Subjects
- Female, Humans, Kelch-Like ECH-Associated Protein 1 genetics, Membrane Proteins metabolism, NF-E2-Related Factor 2 genetics, NF-E2-Related Factor 2 metabolism, Vesicular Transport Proteins metabolism, Breast Neoplasms drug therapy, Breast Neoplasms genetics, Cisplatin pharmacology, Cisplatin therapeutic use, Drug Resistance, Neoplasm genetics
- Abstract
Objective: Cisplatin is the first-line treatment for breast cancer, but it faces challenges of drug resistance. This study investigated new molecular mechanisms underlying cisplatin resistance in breast cancer., Methods: We analyzed sequencing data from the TCGA database to identify potential associations between transmembrane emp24 protein transport domain containing 2 (TMED2) and breast cancer. Western blotting, real-time PCR, CCK-8, and TUNEL assays were used to measure the effects and molecular mechanism of TMED2 on cisplatin resistance in MCF-7 and MDA-MB-231 cell lines., Results: TMED2 was overexpressed in breast cancer and associated with poor prognosis. TMED2 increased cisplatin resistance in breast cancer cells in vitro via promoting ubiquitination of Kelch-like ECH-associated protein 1 (KEAP1), relieving inhibition of KEAP1 on nuclear factor erythroid 2-related factor 2 (Nrf2), and increasing expression of downstream drug resistance related genes, such as heme oxygenase 1 (HO-1) and NAD (P) H quinone oxidoreductase 1 (NQO1)., Conclusion: We identified a new molecular mechanism by which TMED2 affects cisplatin resistance in breast cancer. Our results provide theoretical guidance for future clinical applications., (© 2023. Huazhong University of Science and Technology.)
- Published
- 2023
- Full Text
- View/download PDF