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TMED2 Induces Cisplatin Resistance in Breast Cancer via Targeting the KEAP1-Nrf2 Pathway
Chen Liang1, Han-Yong Zhang2, Yi-Qian Wang1
1College of Life Sciences and Health, Wuhan University of Science and Technology, Wuhan, 430070, China.
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.
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