J 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 KHAIRNAR

Basic 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

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
Name: Národní ústav pro neurologický výzkum
Investor: Ministry of Education, Youth and Sports of the CR, 5.1 EXCELES