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Novel Breast-Specific Long Non-coding RNA LINC00993 Acts as a Tumor Suppressor in Triple-Negative Breast Cancer

Background: Triple-negative breast cancer (TNBC) was characterized by breast cancers that do not express estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor (HER)-2 genes. TNBC patients are associated with a shorter median time to relapse and death for the l...

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Autores principales: Guo, Shipeng, Jian, Lei, Tao, Kai, Chen, Chen, Yu, Haochen, Liu, Shengchun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6928780/
https://www.ncbi.nlm.nih.gov/pubmed/31921620
http://dx.doi.org/10.3389/fonc.2019.01325
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author Guo, Shipeng
Jian, Lei
Tao, Kai
Chen, Chen
Yu, Haochen
Liu, Shengchun
author_facet Guo, Shipeng
Jian, Lei
Tao, Kai
Chen, Chen
Yu, Haochen
Liu, Shengchun
author_sort Guo, Shipeng
collection PubMed
description Background: Triple-negative breast cancer (TNBC) was characterized by breast cancers that do not express estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor (HER)-2 genes. TNBC patients are associated with a shorter median time to relapse and death for the lack of available treatment targets. Long non-coding RNAs (LncRNAs) have been reported to play an important role in the development of TNBC. We identified a novel breast-specific long non-coding RNA LINC00993, but less was known about its expression pattern and functional role in TNBC. Methods: LINC00993 RNA expression was detected across different types of clinical breast cancer samples by using qRT-PCR. Bioinformatic methods “guilt by association” and gene set enrichment analysis (GSEA) were used to predict LINC00993 functions. Subcellular localization of LINC00993 in cells was detected by RNA fluorescence in situ hybridization (FISH). Effect of LINC00993 on cell growth was measured by plate colony formation assays, typical growth curve, and an in vivo tumor model. Cell cycle analysis was done by flow cytometry analysis. Key cell cycle regulators were detected by Western blot. Results: LINC00993 was largely downregulated in TNBC, and higher expression indicated better outcome. LINC00993 located mainly in the nucleus. LINC00993 suppressed TNBC growth both in vitro and in vivo. LINC00993 was predicted to be involved in cell cycle pathways by using “guilt by association” and GSEA methods. Key cell cycle regulators like p16(INK4A), p14(ARF), p53, and p21 were affected by LINC00993 overexpression. Conclusions: A new breast-specific lincRNA LINC00993 was identified with a tumor-suppressive feature and with prognostic value. This is the first research on LINC00993 function. Our results suggest that controlling LINC00993 level may be beneficial for breast cancer treatment.
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spelling pubmed-69287802020-01-09 Novel Breast-Specific Long Non-coding RNA LINC00993 Acts as a Tumor Suppressor in Triple-Negative Breast Cancer Guo, Shipeng Jian, Lei Tao, Kai Chen, Chen Yu, Haochen Liu, Shengchun Front Oncol Oncology Background: Triple-negative breast cancer (TNBC) was characterized by breast cancers that do not express estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor (HER)-2 genes. TNBC patients are associated with a shorter median time to relapse and death for the lack of available treatment targets. Long non-coding RNAs (LncRNAs) have been reported to play an important role in the development of TNBC. We identified a novel breast-specific long non-coding RNA LINC00993, but less was known about its expression pattern and functional role in TNBC. Methods: LINC00993 RNA expression was detected across different types of clinical breast cancer samples by using qRT-PCR. Bioinformatic methods “guilt by association” and gene set enrichment analysis (GSEA) were used to predict LINC00993 functions. Subcellular localization of LINC00993 in cells was detected by RNA fluorescence in situ hybridization (FISH). Effect of LINC00993 on cell growth was measured by plate colony formation assays, typical growth curve, and an in vivo tumor model. Cell cycle analysis was done by flow cytometry analysis. Key cell cycle regulators were detected by Western blot. Results: LINC00993 was largely downregulated in TNBC, and higher expression indicated better outcome. LINC00993 located mainly in the nucleus. LINC00993 suppressed TNBC growth both in vitro and in vivo. LINC00993 was predicted to be involved in cell cycle pathways by using “guilt by association” and GSEA methods. Key cell cycle regulators like p16(INK4A), p14(ARF), p53, and p21 were affected by LINC00993 overexpression. Conclusions: A new breast-specific lincRNA LINC00993 was identified with a tumor-suppressive feature and with prognostic value. This is the first research on LINC00993 function. Our results suggest that controlling LINC00993 level may be beneficial for breast cancer treatment. Frontiers Media S.A. 2019-12-17 /pmc/articles/PMC6928780/ /pubmed/31921620 http://dx.doi.org/10.3389/fonc.2019.01325 Text en Copyright © 2019 Guo, Jian, Tao, Chen, Yu and Liu. http://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
Guo, Shipeng
Jian, Lei
Tao, Kai
Chen, Chen
Yu, Haochen
Liu, Shengchun
Novel Breast-Specific Long Non-coding RNA LINC00993 Acts as a Tumor Suppressor in Triple-Negative Breast Cancer
title Novel Breast-Specific Long Non-coding RNA LINC00993 Acts as a Tumor Suppressor in Triple-Negative Breast Cancer
title_full Novel Breast-Specific Long Non-coding RNA LINC00993 Acts as a Tumor Suppressor in Triple-Negative Breast Cancer
title_fullStr Novel Breast-Specific Long Non-coding RNA LINC00993 Acts as a Tumor Suppressor in Triple-Negative Breast Cancer
title_full_unstemmed Novel Breast-Specific Long Non-coding RNA LINC00993 Acts as a Tumor Suppressor in Triple-Negative Breast Cancer
title_short Novel Breast-Specific Long Non-coding RNA LINC00993 Acts as a Tumor Suppressor in Triple-Negative Breast Cancer
title_sort novel breast-specific long non-coding rna linc00993 acts as a tumor suppressor in triple-negative breast cancer
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6928780/
https://www.ncbi.nlm.nih.gov/pubmed/31921620
http://dx.doi.org/10.3389/fonc.2019.01325
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