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@article{2292994,
author = {Nalla, Lakshmi Vineela and Khairnar, Amit Suresh},
article_location = {AMSTERDAM},
article_number = {March 2023},
doi = {http://dx.doi.org/10.1016/j.ejphar.2023.175565},
keywords = {Stemness; Breast cancer; Empagliflozin; miR-128-3p; PKM2; CD44; CD24},
language = {eng},
issn = {0014-2999},
journal = {European Journal of Pharmacology},
title = {Empagliflozin mediated miR-128-3p upregulation promotes differentiation of hypoxic cancer stem-like cells in breast cancer},
url = {https://www.sciencedirect.com/science/article/pii/S0014299923000766?via%3Dihub},
volume = {943},
year = {2023}
}
TY - JOUR
ID - 2292994
AU - Nalla, Lakshmi Vineela - Khairnar, Amit Suresh
PY - 2023
TI - Empagliflozin mediated miR-128-3p upregulation promotes differentiation of hypoxic cancer stem-like cells in breast cancer
JF - European Journal of Pharmacology
VL - 943
IS - March 2023
SP - 1-14
EP - 1-14
PB - Elsevier
SN - 00142999
KW - Stemness
KW - Breast cancer
KW - Empagliflozin
KW - miR-128-3p
KW - PKM2
KW - CD44
KW - CD24
UR - https://www.sciencedirect.com/science/article/pii/S0014299923000766?via%3Dihub
N2 - 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.
ER -
NALLA, Lakshmi Vineela and Amit Suresh KHAIRNAR. Empagliflozin mediated miR-128-3p upregulation promotes differentiation of hypoxic cancer stem-like cells in breast cancer. \textit{European Journal of Pharmacology}. AMSTERDAM: Elsevier, 2023, vol.~943, March 2023, p.~1-14. ISSN~0014-2999. Available from: https://dx.doi.org/10.1016/j.ejphar.2023.175565.
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