Empagliflozin drives ferroptosis in anoikis-resistant cells by activating miR-128-3p dependent pathway and inhibiting CD98hc in breast cancer
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00159816%3A_____%2F24%3A00081399" target="_blank" >RIV/00159816:_____/24:00081399 - isvavai.cz</a>
Alternative codes found
RIV/00216224:14110/24:00136353
Result on the web
<a href="https://www.sciencedirect.com/science/article/abs/pii/S0891584924004532?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/abs/pii/S0891584924004532?via%3Dihub</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.freeradbiomed.2024.05.018" target="_blank" >10.1016/j.freeradbiomed.2024.05.018</a>
Alternative languages
Result language
angličtina
Original language name
Empagliflozin drives ferroptosis in anoikis-resistant cells by activating miR-128-3p dependent pathway and inhibiting CD98hc in breast cancer
Original language description
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.
Czech name
—
Czech description
—
Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
<a href="/en/project/LX22NPO5107" target="_blank" >LX22NPO5107: National institute for Neurological Research</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Free Radical Biology and Medicine
ISSN
0891-5849
e-ISSN
1873-4596
Volume of the periodical
220
Issue of the periodical within the volume
AUG
Country of publishing house
US - UNITED STATES
Number of pages
13
Pages from-to
288-300
UT code for WoS article
001242109800001
EID of the result in the Scopus database
—