Detailed Information on Publication Record
2024
Empagliflozin drives ferroptosis in anoikis-resistant cells by activating miR-128-3p dependent pathway and inhibiting CD98hc in breast cancer
NALLA, Lakshmi Vineela and Amit Suresh KHAIRNARBasic information
Original name
Empagliflozin drives ferroptosis in anoikis-resistant cells by activating miR-128-3p dependent pathway and inhibiting CD98hc in breast cancer
Authors
NALLA, Lakshmi Vineela and Amit Suresh KHAIRNAR (356 India, belonging to the institution)
Edition
Free Radical Biology and Medicine, NEW YORK, ELSEVIER SCIENCE INC, 2024, 0891-5849
Other information
Language
English
Type of outcome
Článek v odborném periodiku
Field of Study
30204 Oncology
Country of publisher
United States of America
Confidentiality degree
není předmětem státního či obchodního tajemství
References:
Impact factor
Impact factor: 7.400 in 2022
Organization unit
Faculty of Medicine
UT WoS
001242109800001
Keywords in English
Ferroptosis; Reactive oxygen species; Breast cancer; Metastasis; Anoikis resistance
Tags
International impact, Reviewed
Změněno: 1/7/2024 13:41, Mgr. Tereza Miškechová
Abstract
V originále
A tumour suppressor miRNA, miR-128-3p, is widely involved in various biological processes and has been found to get downregulated in breast cancer patients. We previously published that ectopically expressed miR-128-3p suppressed migration, invasion, cell cycle arrest, and breast cancer stem cells. In the present study, we explored the role of Empagliflozin (EMPA) as a miR-128-3p functionality-mimicking drug in inducing ferroptosis by inhibiting CD98hc. Given that CD98hc is one of the proteins critical in triggering ferroptosis, we confirmed that miR-128-3p and EMPA inhibited SP1, leading to inhibition of CD98hc expression. Further, transfection with siCD98hc, miR-128-3p mimics, and inhibitors was performed to assess their involvement in the ferroptosis of anoikis-resistant cells. We proved that anoikis-resistant cells possess high ROS and iron levels. Further, miR-1283p and EMPA treatments induced ferroptosis by inhibiting GSH and enzymatic activity of GPX4 and also induced lipid peroxidation. Moreover, EMPA suppressed bioluminescence of 4T1-Red-FLuc induced thoracic cavity, peritoneal tumour burden and lung nodules in an in-vivo metastatic model of breast cancer. Collectively, we revealed that EMPA sensitized the ECM detached cells to ferroptosis by synergically activating miR-128-3p and lowering the levels of SP1 and CD98hc, making it a potential adjunct drug for breast cancer chemotherapy.
Links
| LX22NPO5107, research and development project |
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