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LncRNA CARMN overexpression promotes prognosis and chemosensitivity of triple negative breast cancer via acting as miR143-3p host gene and inhibiting DNA replication

BACKGROUND: Triple negative breast cancer (TNBC) is a subtype of breast cancer with poor prognosis and lack of effective treatment target. Here we screened differentially expressed lncRNAs through bioinformatics analysis and identified CARMN as a downregulated lncRNA which is lowest expressed in TNB...

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Autores principales: Sheng, Xiaonan, Dai, Huijuan, Du, Yueyao, Peng, Jing, Sha, Rui, Yang, Fan, Zhou, Liheng, Lin, Yanping, Xu, Shuguang, Wu, Yifan, Yin, Wenjin, Lu, Jinsong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220716/
https://www.ncbi.nlm.nih.gov/pubmed/34162418
http://dx.doi.org/10.1186/s13046-021-02015-4
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author Sheng, Xiaonan
Dai, Huijuan
Du, Yueyao
Peng, Jing
Sha, Rui
Yang, Fan
Zhou, Liheng
Lin, Yanping
Xu, Shuguang
Wu, Yifan
Yin, Wenjin
Lu, Jinsong
author_facet Sheng, Xiaonan
Dai, Huijuan
Du, Yueyao
Peng, Jing
Sha, Rui
Yang, Fan
Zhou, Liheng
Lin, Yanping
Xu, Shuguang
Wu, Yifan
Yin, Wenjin
Lu, Jinsong
author_sort Sheng, Xiaonan
collection PubMed
description BACKGROUND: Triple negative breast cancer (TNBC) is a subtype of breast cancer with poor prognosis and lack of effective treatment target. Here we screened differentially expressed lncRNAs through bioinformatics analysis and identified CARMN as a downregulated lncRNA which is lowest expressed in TNBC. We aimed to identify the potential role and molecular mechanisms of CARMN in TNBC. METHODS: Predictive value of CARMN was explored in breast cancer cohorts. TNBC cell lines with CARMN overexpression or CARMN silence and were used for in vitro and in vivo experiments. RNA-seq of CARMN overexpressed cells was performed for exploring downstream of CARMN. RESULTS: CARMN is downregulated at different phase of malignant transformation of breast tissue. CARMN can predict both better prognosis and higher response rate of cisplatin-based neoadjuvant chemotherapy in breast cancer. A nomogram is built to predict cisplatin-based chemotherapy response in breast cancer. Through in vitro and in vivo studies, we confirmed CARMN can also inhibit tumorigenesis and enhance sensitivity to cisplatin in TNBC cells. RNA-seq and further experiments revealed CARMN can inhibit DNA replication. MCM5, an important DNA replication initiation factor, is the most downregulated gene in DNA replication pathway following CARMN overexpression. We confirmed CARMN can produce miR143-3p from its exon5 which is DROSHA and DICER dependent, resulting binding and decrease of MCM5. Moreover, suppressing miR143-3p can weaken function of CARMN in suppressing tumorigenesis and promoting chemosensitivity. CONCLUSIONS: Our results indicated lncRNA CARMN is a predictive biomarker of better prognosis and enhanced cisplatin sensitivity in TNBC. CARMN is the host gene of miR143-3p which downregulates MCM5, causing inhibited DNA replication. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13046-021-02015-4.
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spelling pubmed-82207162021-06-23 LncRNA CARMN overexpression promotes prognosis and chemosensitivity of triple negative breast cancer via acting as miR143-3p host gene and inhibiting DNA replication Sheng, Xiaonan Dai, Huijuan Du, Yueyao Peng, Jing Sha, Rui Yang, Fan Zhou, Liheng Lin, Yanping Xu, Shuguang Wu, Yifan Yin, Wenjin Lu, Jinsong J Exp Clin Cancer Res Research BACKGROUND: Triple negative breast cancer (TNBC) is a subtype of breast cancer with poor prognosis and lack of effective treatment target. Here we screened differentially expressed lncRNAs through bioinformatics analysis and identified CARMN as a downregulated lncRNA which is lowest expressed in TNBC. We aimed to identify the potential role and molecular mechanisms of CARMN in TNBC. METHODS: Predictive value of CARMN was explored in breast cancer cohorts. TNBC cell lines with CARMN overexpression or CARMN silence and were used for in vitro and in vivo experiments. RNA-seq of CARMN overexpressed cells was performed for exploring downstream of CARMN. RESULTS: CARMN is downregulated at different phase of malignant transformation of breast tissue. CARMN can predict both better prognosis and higher response rate of cisplatin-based neoadjuvant chemotherapy in breast cancer. A nomogram is built to predict cisplatin-based chemotherapy response in breast cancer. Through in vitro and in vivo studies, we confirmed CARMN can also inhibit tumorigenesis and enhance sensitivity to cisplatin in TNBC cells. RNA-seq and further experiments revealed CARMN can inhibit DNA replication. MCM5, an important DNA replication initiation factor, is the most downregulated gene in DNA replication pathway following CARMN overexpression. We confirmed CARMN can produce miR143-3p from its exon5 which is DROSHA and DICER dependent, resulting binding and decrease of MCM5. Moreover, suppressing miR143-3p can weaken function of CARMN in suppressing tumorigenesis and promoting chemosensitivity. CONCLUSIONS: Our results indicated lncRNA CARMN is a predictive biomarker of better prognosis and enhanced cisplatin sensitivity in TNBC. CARMN is the host gene of miR143-3p which downregulates MCM5, causing inhibited DNA replication. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13046-021-02015-4. BioMed Central 2021-06-23 /pmc/articles/PMC8220716/ /pubmed/34162418 http://dx.doi.org/10.1186/s13046-021-02015-4 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Sheng, Xiaonan
Dai, Huijuan
Du, Yueyao
Peng, Jing
Sha, Rui
Yang, Fan
Zhou, Liheng
Lin, Yanping
Xu, Shuguang
Wu, Yifan
Yin, Wenjin
Lu, Jinsong
LncRNA CARMN overexpression promotes prognosis and chemosensitivity of triple negative breast cancer via acting as miR143-3p host gene and inhibiting DNA replication
title LncRNA CARMN overexpression promotes prognosis and chemosensitivity of triple negative breast cancer via acting as miR143-3p host gene and inhibiting DNA replication
title_full LncRNA CARMN overexpression promotes prognosis and chemosensitivity of triple negative breast cancer via acting as miR143-3p host gene and inhibiting DNA replication
title_fullStr LncRNA CARMN overexpression promotes prognosis and chemosensitivity of triple negative breast cancer via acting as miR143-3p host gene and inhibiting DNA replication
title_full_unstemmed LncRNA CARMN overexpression promotes prognosis and chemosensitivity of triple negative breast cancer via acting as miR143-3p host gene and inhibiting DNA replication
title_short LncRNA CARMN overexpression promotes prognosis and chemosensitivity of triple negative breast cancer via acting as miR143-3p host gene and inhibiting DNA replication
title_sort lncrna carmn overexpression promotes prognosis and chemosensitivity of triple negative breast cancer via acting as mir143-3p host gene and inhibiting dna replication
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220716/
https://www.ncbi.nlm.nih.gov/pubmed/34162418
http://dx.doi.org/10.1186/s13046-021-02015-4
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