Empagliflozin mediated miR-128-3p upregulation promotes differentiation of hypoxic cancer stem-like cells in breast cancer

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00159816%3A_____%2F23%3A00079713" target="_blank" >RIV/00159816:_____/23:00079713 - isvavai.cz</a>

Alternative codes found

RIV/00216224:14110/23:00131027

Result on the web

<a href="https://www.sciencedirect.com/science/article/abs/pii/S0014299923000766?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/abs/pii/S0014299923000766?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.ejphar.2023.175565" target="_blank" >10.1016/j.ejphar.2023.175565</a>

Result language

angličtina

Original language name

Empagliflozin mediated miR-128-3p upregulation promotes differentiation of hypoxic cancer stem-like cells in breast cancer

Original language description

Aims: The hsa-miR-128-3p expression is downregulated in advanced breast cancer patients. Empagliflozin (EMPA) is an anti-diabetic drug with anticancer potential. The present study investigated the effect of EMPA on cancer cell differentiation by acting as a miR-128-3p mimicking drug in breast cancer.Main methods: Our results first demonstrate SP1 and PKM2 as the downstream effectors of hsa-miR-128-3p. Further, transfection with siPKM2, miR-128-3p mimics, and inhibitors was performed to assess their involve-ment in cancer stemness using flow cytometry. Further, EMPA as miR-128-3p mimicking drug was screened and explored on cancer cell differentiation. Then, we treated the 4T1-Red-FLuc allograft breast tumor with EMPA to assess its inhibitory potential toward tumor growth using IVIS (R) Spectrum. Immunohistochemistry was per-formed to evaluate cancer cell differentiation and cell proliferation.Key findings: We found that hsa-miR-128-3p is the upstream regulator of SP1 and PKM2 in hypoxic breast cancer cells. Overexpression of miR-128-3p with mimics downregulate SP1 and PKM2, whereas miR-128-3p inhibitor shows an opposite effect. The enhanced expression of miR-128-3p and PKM2 knockdown diminishes hypoxia-induced CD44 expression and enhance CD44+/CD24+ differentiated cells. We also identified EMPA as the miR-128-3p mimicking drug that can enhance the differentiated cell population. Further, EMPA suppressed in vivo tumor growth, lung metastasis, tumor bioluminescence, and cell proliferation. Therefore, EMPA abrogates breast cancer stemness by inactivating SP1 and PKM2 via enhanced miR-128-3p expression.Significance: EMPA could be a promising drug in combination with other chemotherapeutic drugs in advanced breast cancer.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30104 - Pharmacology and pharmacy

Project

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Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2023

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

European journal of pharmacology

ISSN

0014-2999

e-ISSN

1879-0712

Volume of the periodical

943

Issue of the periodical within the volume

MAR 2023

Country of publishing house

US - UNITED STATES

Number of pages

14

Pages from-to

175565

UT code for WoS article

000944731500001

EID of the result in the Scopus database

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