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A feedback loop between lncRNA MALAT1 and DNMT1 promotes triple-negative breast cancer stemness and tumorigenesis

BACKGROUND: The function of long non-coding RNA (lncRNA) MALAT1 in regulating triple-negative breast cancer (TNBC) stemness and tumorigenesis was investigated. METHODS: Sphere formation and colony formation assays coupled with flow cytometry were employed to evaluate the percentage of CD44(high)/CD4...

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Autores principales: Hu, Yu, He, Yuqiong, Luo, Na, Li, Xin, Guo, Lei, Zhang, Kejing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10408694/
https://www.ncbi.nlm.nih.gov/pubmed/37548553
http://dx.doi.org/10.1080/15384047.2023.2235768
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author Hu, Yu
He, Yuqiong
Luo, Na
Li, Xin
Guo, Lei
Zhang, Kejing
author_facet Hu, Yu
He, Yuqiong
Luo, Na
Li, Xin
Guo, Lei
Zhang, Kejing
author_sort Hu, Yu
collection PubMed
description BACKGROUND: The function of long non-coding RNA (lncRNA) MALAT1 in regulating triple-negative breast cancer (TNBC) stemness and tumorigenesis was investigated. METHODS: Sphere formation and colony formation assays coupled with flow cytometry were employed to evaluate the percentage of CD44(high)/CD44(low) cells, and ALDH(+) cells were performed to evaluate the stemness. Bisulfite sequencing PCR (BSP) was employed to detect the methylation level of MALAT1. Tumor xenograft experiment was performed to evaluate tumorigenesis in vivo. Finally, dual-luciferase reporter and RIP assays were employed to verify the binding relationship between MALAT1 and miR-137. RESULTS: Our results revealed that MALAT1 and BCL11A were highly expressed in TNBC, while miR-137 and DNMT1 were lowly expressed. Our results proved that MALAT1 positively regulated BCL11A expression through targeting miR-137. Functional experiments revealed that MALAT1 inhibited DNMT1 expression through acting on the miR-137/BCL11A pathway to enhance TNBC stemness and tumorigenesis. We also found that high MALAT1 expression in TNBC was related to the DNMT1-mediated hypomethylation of MALAT1. As expected, DNMT1 overexpression could remarkably inhibit TNBC stemness and tumorigenesis, which was eliminated by MALAT1 overexpression. CONCLUSION: MALAT1 downregulated DNMT1 by miR-137/BCL11A pathway to enhance TNBC stemness and tumorigenesis; meanwhile, DNMT1/MALAT1 formed a positive feedback loop to continuously promote TNBC malignant behaviors.
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spelling pubmed-104086942023-08-09 A feedback loop between lncRNA MALAT1 and DNMT1 promotes triple-negative breast cancer stemness and tumorigenesis Hu, Yu He, Yuqiong Luo, Na Li, Xin Guo, Lei Zhang, Kejing Cancer Biol Ther Research Paper BACKGROUND: The function of long non-coding RNA (lncRNA) MALAT1 in regulating triple-negative breast cancer (TNBC) stemness and tumorigenesis was investigated. METHODS: Sphere formation and colony formation assays coupled with flow cytometry were employed to evaluate the percentage of CD44(high)/CD44(low) cells, and ALDH(+) cells were performed to evaluate the stemness. Bisulfite sequencing PCR (BSP) was employed to detect the methylation level of MALAT1. Tumor xenograft experiment was performed to evaluate tumorigenesis in vivo. Finally, dual-luciferase reporter and RIP assays were employed to verify the binding relationship between MALAT1 and miR-137. RESULTS: Our results revealed that MALAT1 and BCL11A were highly expressed in TNBC, while miR-137 and DNMT1 were lowly expressed. Our results proved that MALAT1 positively regulated BCL11A expression through targeting miR-137. Functional experiments revealed that MALAT1 inhibited DNMT1 expression through acting on the miR-137/BCL11A pathway to enhance TNBC stemness and tumorigenesis. We also found that high MALAT1 expression in TNBC was related to the DNMT1-mediated hypomethylation of MALAT1. As expected, DNMT1 overexpression could remarkably inhibit TNBC stemness and tumorigenesis, which was eliminated by MALAT1 overexpression. CONCLUSION: MALAT1 downregulated DNMT1 by miR-137/BCL11A pathway to enhance TNBC stemness and tumorigenesis; meanwhile, DNMT1/MALAT1 formed a positive feedback loop to continuously promote TNBC malignant behaviors. Taylor & Francis 2023-08-07 /pmc/articles/PMC10408694/ /pubmed/37548553 http://dx.doi.org/10.1080/15384047.2023.2235768 Text en © 2023 The Author(s). Published with license by Taylor & Francis Group, LLC. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent.
spellingShingle Research Paper
Hu, Yu
He, Yuqiong
Luo, Na
Li, Xin
Guo, Lei
Zhang, Kejing
A feedback loop between lncRNA MALAT1 and DNMT1 promotes triple-negative breast cancer stemness and tumorigenesis
title A feedback loop between lncRNA MALAT1 and DNMT1 promotes triple-negative breast cancer stemness and tumorigenesis
title_full A feedback loop between lncRNA MALAT1 and DNMT1 promotes triple-negative breast cancer stemness and tumorigenesis
title_fullStr A feedback loop between lncRNA MALAT1 and DNMT1 promotes triple-negative breast cancer stemness and tumorigenesis
title_full_unstemmed A feedback loop between lncRNA MALAT1 and DNMT1 promotes triple-negative breast cancer stemness and tumorigenesis
title_short A feedback loop between lncRNA MALAT1 and DNMT1 promotes triple-negative breast cancer stemness and tumorigenesis
title_sort feedback loop between lncrna malat1 and dnmt1 promotes triple-negative breast cancer stemness and tumorigenesis
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10408694/
https://www.ncbi.nlm.nih.gov/pubmed/37548553
http://dx.doi.org/10.1080/15384047.2023.2235768
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