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Upregulation of miR‐374a promotes tumor metastasis and progression by downregulating LACTB and predicts unfavorable prognosis in breast cancer

Breast cancer (BRCA) is the second leading cause of cancer‐related death among female worldwide. Recent studies have revealed that LACTB was frequently repressed and functioned as a bona fide new tumor suppressor in a series of cancers, including BRCA. However, the molecular mechanisms underlying LA...

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Autores principales: Zhang, Jun, He, Yuting, Yu, Yan, Chen, Xiaolong, Cui, Guangying, Wang, Weiwei, Zhang, Xiaojian, Luo, Yonggang, Li, Juan, Ren, Fang, Ren, Zhigang, Sun, Ranran
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6051141/
https://www.ncbi.nlm.nih.gov/pubmed/29790671
http://dx.doi.org/10.1002/cam4.1576
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author Zhang, Jun
He, Yuting
Yu, Yan
Chen, Xiaolong
Cui, Guangying
Wang, Weiwei
Zhang, Xiaojian
Luo, Yonggang
Li, Juan
Ren, Fang
Ren, Zhigang
Sun, Ranran
author_facet Zhang, Jun
He, Yuting
Yu, Yan
Chen, Xiaolong
Cui, Guangying
Wang, Weiwei
Zhang, Xiaojian
Luo, Yonggang
Li, Juan
Ren, Fang
Ren, Zhigang
Sun, Ranran
author_sort Zhang, Jun
collection PubMed
description Breast cancer (BRCA) is the second leading cause of cancer‐related death among female worldwide. Recent studies have revealed that LACTB was frequently repressed and functioned as a bona fide new tumor suppressor in a series of cancers, including BRCA. However, the molecular mechanisms underlying LACTB dysregulation in BRCA have not been reported. In the present study, we find that LACTB is repressed in BRCA and associated with poor prognosis by BRCA tissue microarray (TMA) analysis. Moreover, we confirm that LACTB is a direct target of miR‐374a, which is significantly overexpressed and associated with malignancies in BRCA. Mechanistically, applying loss‐of‐function and gain‐of‐function approaches in a series of in vitro and in vivo experiments show that miR‐374a knockdown suppresses the cell proliferative and colony formation activity, as well as migration and invasion capacity, but LACTB silencing in these cells reverses this change. Furthermore, we find that miR‐374a silencing markedly reduces the tumor growth in xenograft mouse models. In summary, our findings suggest the miR‐374a/LACTB axis plays a critical role in the tumorigenicity and progression of BRCA. miR‐374a/LACTB axis may be a potential target in the development of therapeutic strategies for BRCA patients.
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spelling pubmed-60511412018-07-20 Upregulation of miR‐374a promotes tumor metastasis and progression by downregulating LACTB and predicts unfavorable prognosis in breast cancer Zhang, Jun He, Yuting Yu, Yan Chen, Xiaolong Cui, Guangying Wang, Weiwei Zhang, Xiaojian Luo, Yonggang Li, Juan Ren, Fang Ren, Zhigang Sun, Ranran Cancer Med Cancer Biology Breast cancer (BRCA) is the second leading cause of cancer‐related death among female worldwide. Recent studies have revealed that LACTB was frequently repressed and functioned as a bona fide new tumor suppressor in a series of cancers, including BRCA. However, the molecular mechanisms underlying LACTB dysregulation in BRCA have not been reported. In the present study, we find that LACTB is repressed in BRCA and associated with poor prognosis by BRCA tissue microarray (TMA) analysis. Moreover, we confirm that LACTB is a direct target of miR‐374a, which is significantly overexpressed and associated with malignancies in BRCA. Mechanistically, applying loss‐of‐function and gain‐of‐function approaches in a series of in vitro and in vivo experiments show that miR‐374a knockdown suppresses the cell proliferative and colony formation activity, as well as migration and invasion capacity, but LACTB silencing in these cells reverses this change. Furthermore, we find that miR‐374a silencing markedly reduces the tumor growth in xenograft mouse models. In summary, our findings suggest the miR‐374a/LACTB axis plays a critical role in the tumorigenicity and progression of BRCA. miR‐374a/LACTB axis may be a potential target in the development of therapeutic strategies for BRCA patients. John Wiley and Sons Inc. 2018-05-23 /pmc/articles/PMC6051141/ /pubmed/29790671 http://dx.doi.org/10.1002/cam4.1576 Text en © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Cancer Biology
Zhang, Jun
He, Yuting
Yu, Yan
Chen, Xiaolong
Cui, Guangying
Wang, Weiwei
Zhang, Xiaojian
Luo, Yonggang
Li, Juan
Ren, Fang
Ren, Zhigang
Sun, Ranran
Upregulation of miR‐374a promotes tumor metastasis and progression by downregulating LACTB and predicts unfavorable prognosis in breast cancer
title Upregulation of miR‐374a promotes tumor metastasis and progression by downregulating LACTB and predicts unfavorable prognosis in breast cancer
title_full Upregulation of miR‐374a promotes tumor metastasis and progression by downregulating LACTB and predicts unfavorable prognosis in breast cancer
title_fullStr Upregulation of miR‐374a promotes tumor metastasis and progression by downregulating LACTB and predicts unfavorable prognosis in breast cancer
title_full_unstemmed Upregulation of miR‐374a promotes tumor metastasis and progression by downregulating LACTB and predicts unfavorable prognosis in breast cancer
title_short Upregulation of miR‐374a promotes tumor metastasis and progression by downregulating LACTB and predicts unfavorable prognosis in breast cancer
title_sort upregulation of mir‐374a promotes tumor metastasis and progression by downregulating lactb and predicts unfavorable prognosis in breast cancer
topic Cancer Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6051141/
https://www.ncbi.nlm.nih.gov/pubmed/29790671
http://dx.doi.org/10.1002/cam4.1576
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