Empagliflozin drives ferroptosis in anoikis-resistant cells by
activating miR-128-3p dependent pathway and inhibiting CD98hc
in breast cancer

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 a Amit Suresh KHAIRNAR

Základní údaje

Originální název

Empagliflozin drives ferroptosis in anoikis-resistant cells by activating miR-128-3p dependent pathway and inhibiting CD98hc in breast cancer

Autoři

NALLA, Lakshmi Vineela a Amit Suresh KHAIRNAR (356 Indie, domácí)

Vydání

Free Radical Biology and Medicine, NEW YORK, ELSEVIER SCIENCE INC, 2024, 0891-5849

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30204 Oncology

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 7.400 v roce 2022

Organizační jednotka

Lékařská fakulta

DOI

http://dx.doi.org/10.1016/j.freeradbiomed.2024.05.018

UT WoS

001242109800001

Klíčová slova anglicky

Ferroptosis; Reactive oxygen species; Breast cancer; Metastasis; Anoikis resistance

Štítky

14110515, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 1. 7. 2024 13:41, Mgr. Tereza Miškechová

Anotace

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.

Návaznosti

LX22NPO5107, projekt VaV

Název: Národní ústav pro neurologický výzkum

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Národní ústav pro neurologický výzkum, 5.1 EXCELES

Citovat

NALLA, Lakshmi Vineela a Amit Suresh KHAIRNAR. Empagliflozin drives ferroptosis in anoikis-resistant cells by activating miR-128-3p dependent pathway and inhibiting CD98hc in breast cancer. Free Radical Biology and Medicine. NEW YORK: ELSEVIER SCIENCE INC, 2024, roč. 220, August 2024, s. 288-300. ISSN 0891-5849. Dostupné z: https://dx.doi.org/10.1016/j.freeradbiomed.2024.05.018.

@article{2415997,
   author = {Nalla, Lakshmi Vineela and Khairnar, Amit Suresh},
   article_location = {NEW YORK},
   article_number = {August 2024},
   doi = {http://dx.doi.org/10.1016/j.freeradbiomed.2024.05.018},
   keywords = {Ferroptosis; Reactive oxygen species; Breast cancer; Metastasis; Anoikis resistance},
   language = {eng},
   issn = {0891-5849},
   journal = {Free Radical Biology and Medicine},
   title = {Empagliflozin drives ferroptosis in anoikis-resistant cells by activating miR-128-3p dependent pathway and inhibiting CD98hc in breast cancer},
   url = {https://www.sciencedirect.com/science/article/pii/S0891584924004532?via%3Dihub},
   volume = {220},
   year = {2024}
}

TY  - JOUR
ID  - 2415997
AU  - Nalla, Lakshmi Vineela - Khairnar, Amit Suresh
PY  - 2024
TI  - Empagliflozin drives ferroptosis in anoikis-resistant cells by activating miR-128-3p dependent pathway and inhibiting CD98hc in breast cancer
JF  - Free Radical Biology and Medicine
VL  - 220
IS  - August 2024
SP  - 288-300
EP  - 288-300
PB  - ELSEVIER SCIENCE INC
SN  - 08915849
KW  - Ferroptosis
KW  - Reactive oxygen species
KW  - Breast cancer
KW  - Metastasis
KW  - Anoikis resistance
UR  - https://www.sciencedirect.com/science/article/pii/S0891584924004532?via%3Dihub
N2  - 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.
ER  -

NALLA, Lakshmi Vineela a Amit Suresh KHAIRNAR. Empagliflozin drives ferroptosis in anoikis-resistant cells by activating miR-128-3p dependent pathway and inhibiting CD98hc in breast cancer. \textit{Free Radical Biology and Medicine}. NEW YORK: ELSEVIER SCIENCE INC, 2024, roč.~220, August 2024, s.~288-300. ISSN~0891-5849. Dostupné z: https://dx.doi.org/10.1016/j.freeradbiomed.2024.05.018.

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