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PCDHB17P/miR-145-3p/MELK/NF-κB Feedback Loop Promotes Metastasis and Angiogenesis of Breast Cancer

Breast cancer is one of the most common life-threatening cancers, mainly because of its aggressiveness and metastasis. Accumulating evidence indicates that long non-coding RNAs (lncRNAs) participate in the development and progression of breast cancer. Nevertheless, the function and expression level...

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Autores principales: Zhu, Li, Zhang, Yan-Jun, Wang, Bin, Yang, Li, Zheng, Yi-Qiong, Sun, Lin-De, Tian, Lin, Chen, Tao, Wang, Jian-Dong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8327775/
https://www.ncbi.nlm.nih.gov/pubmed/34350110
http://dx.doi.org/10.3389/fonc.2021.660307
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author Zhu, Li
Zhang, Yan-Jun
Wang, Bin
Yang, Li
Zheng, Yi-Qiong
Sun, Lin-De
Tian, Lin
Chen, Tao
Wang, Jian-Dong
author_facet Zhu, Li
Zhang, Yan-Jun
Wang, Bin
Yang, Li
Zheng, Yi-Qiong
Sun, Lin-De
Tian, Lin
Chen, Tao
Wang, Jian-Dong
author_sort Zhu, Li
collection PubMed
description Breast cancer is one of the most common life-threatening cancers, mainly because of its aggressiveness and metastasis. Accumulating evidence indicates that long non-coding RNAs (lncRNAs) participate in the development and progression of breast cancer. Nevertheless, the function and expression level of lncRNAs in breast cancer are still not fully understood. Here, we demonstrated that lncRNA PCDHB17P was up-expressed in human breast cancer tissues and cell lines. Knockdown of PCDHB17P remarkably suppressed migration and invasion, as well as tube formation ability of breast cancer cells. MiR-145-3p was significantly decreased in breast cancer samples, which was negatively correlated to the expression of PCDHB17P. In addition, we identified that MELK was a direct target gene of miR-145-3p, which was higher expressed in breast cancer tissues than that in adjacent normal tissues. Mechanistic investigation indicated that PCDHB17P acted as a cancer-promoting competing endogenous RNA (ceRNA) by binding miR-145-3p and upregulating MELK. Interestingly, MELK could in turn increase the promoter activity and expression of PCDHB17P via NF-κB, thus forming a positive feedback loop that drives the metastasis and angiogenesis of breast cancer. Overall, the results demonstrated that the constitutive activation of PCDHB17P/miR-145-3p/MELK/NF-κB feedback loop promotes the metastasis and angiogenesis of breast cancer, suggesting that this lncRNA might be a promising prognostic biomarker and therapeutic target for breast cancer.
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spelling pubmed-83277752021-08-03 PCDHB17P/miR-145-3p/MELK/NF-κB Feedback Loop Promotes Metastasis and Angiogenesis of Breast Cancer Zhu, Li Zhang, Yan-Jun Wang, Bin Yang, Li Zheng, Yi-Qiong Sun, Lin-De Tian, Lin Chen, Tao Wang, Jian-Dong Front Oncol Oncology Breast cancer is one of the most common life-threatening cancers, mainly because of its aggressiveness and metastasis. Accumulating evidence indicates that long non-coding RNAs (lncRNAs) participate in the development and progression of breast cancer. Nevertheless, the function and expression level of lncRNAs in breast cancer are still not fully understood. Here, we demonstrated that lncRNA PCDHB17P was up-expressed in human breast cancer tissues and cell lines. Knockdown of PCDHB17P remarkably suppressed migration and invasion, as well as tube formation ability of breast cancer cells. MiR-145-3p was significantly decreased in breast cancer samples, which was negatively correlated to the expression of PCDHB17P. In addition, we identified that MELK was a direct target gene of miR-145-3p, which was higher expressed in breast cancer tissues than that in adjacent normal tissues. Mechanistic investigation indicated that PCDHB17P acted as a cancer-promoting competing endogenous RNA (ceRNA) by binding miR-145-3p and upregulating MELK. Interestingly, MELK could in turn increase the promoter activity and expression of PCDHB17P via NF-κB, thus forming a positive feedback loop that drives the metastasis and angiogenesis of breast cancer. Overall, the results demonstrated that the constitutive activation of PCDHB17P/miR-145-3p/MELK/NF-κB feedback loop promotes the metastasis and angiogenesis of breast cancer, suggesting that this lncRNA might be a promising prognostic biomarker and therapeutic target for breast cancer. Frontiers Media S.A. 2021-07-19 /pmc/articles/PMC8327775/ /pubmed/34350110 http://dx.doi.org/10.3389/fonc.2021.660307 Text en Copyright © 2021 Zhu, Zhang, Wang, Yang, Zheng, Sun, Tian, Chen and Wang https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Zhu, Li
Zhang, Yan-Jun
Wang, Bin
Yang, Li
Zheng, Yi-Qiong
Sun, Lin-De
Tian, Lin
Chen, Tao
Wang, Jian-Dong
PCDHB17P/miR-145-3p/MELK/NF-κB Feedback Loop Promotes Metastasis and Angiogenesis of Breast Cancer
title PCDHB17P/miR-145-3p/MELK/NF-κB Feedback Loop Promotes Metastasis and Angiogenesis of Breast Cancer
title_full PCDHB17P/miR-145-3p/MELK/NF-κB Feedback Loop Promotes Metastasis and Angiogenesis of Breast Cancer
title_fullStr PCDHB17P/miR-145-3p/MELK/NF-κB Feedback Loop Promotes Metastasis and Angiogenesis of Breast Cancer
title_full_unstemmed PCDHB17P/miR-145-3p/MELK/NF-κB Feedback Loop Promotes Metastasis and Angiogenesis of Breast Cancer
title_short PCDHB17P/miR-145-3p/MELK/NF-κB Feedback Loop Promotes Metastasis and Angiogenesis of Breast Cancer
title_sort pcdhb17p/mir-145-3p/melk/nf-κb feedback loop promotes metastasis and angiogenesis of breast cancer
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8327775/
https://www.ncbi.nlm.nih.gov/pubmed/34350110
http://dx.doi.org/10.3389/fonc.2021.660307
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