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- W3217290462 abstract "Abstract Background Breast cancer is the main cause of death among women worldwide. More and more long non-coding RNAs (lncRNAs) have been identified as oncogenes or tumor suppressors during cancer development. However, whether ANRIL is involved in drug resistance in triple-negative breast cancer (TNBC) has not been investigated. Methods Luciferase reporter assay was conducted to verify the binding of miR-125a and ANRIL. RT-PCR and western blot were performed to detect the expression of miR-125a, ANRIL and ENO1. Gene silence and overexpression experiments as well as CCK-8 and colony formation assays on TNBC cell lines were performed to determine the regulation of molecular pathways. Glycolysis analysis was performed with Seahorse extracellular flux methodology. Results ANRIL expression in TNBC patients and TNBC cells was examined and we found that ANRIL expression was upregulated in both TNBC patients and TNBC cell lines. Knockdown of ANRIL increased the cytotoxic effect of ADR and inhibited HIF-1α-dependent glycolysis in TNBC cells. In addition, we found that ANRIL negatively regulated miR-125a expression in TNBC cell lines. Besides, a dual-luciferase reporter assay proved ANRIL functioned as a sponger of miR-125a. Further investigation revealed that ENO1 was a target of miR-125a and positively regulated by ANRIL in TNBC cells. Additionally, ANRIL upregulation reversed miR-125-mediated inhibition on HIF-1α-dependent glycolysis in TNBC cells. More notably, 2-deoxy-glucose (2-DG) attenuated ANRIL-induced increase of drug resistance in TNBC cells. Conclusions Taken together, our study was the first to identify that knockdown of ANRIL plays an active role in overcoming the drug resistance in TNBC by inhibiting glycolysis through the miR-125a/ENO1 pathway, which maybe serve useful for the development of novel therapeutic targets." @default.
- W3217290462 created "2021-12-06" @default.
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- W3217290462 date "2021-11-23" @default.
- W3217290462 modified "2023-10-04" @default.
- W3217290462 title "Long Non-Coding RNA ANRIL Promotes Doxorubicin Resistance in Triple-Negative Breast Cancer via Suppressing Glycolysis Through the MicroRNA-125a/ENO Pathway" @default.
- W3217290462 doi "https://doi.org/10.21203/rs.3.rs-1062354/v1" @default.
- W3217290462 hasPublicationYear "2021" @default.
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