Cargando…

microRNA alterations in ALDH positive mammary epithelial cells: a crucial contributing factor towards breast cancer risk reduction in case of early pregnancy

BACKGROUND: microRNAs have recently succeeded in grabbing the center stage in cancer research for their potential to regulate vital cellular process like cell cycle, stem cell renewal and epithelial mesenchymal transition. Breast cancer is the second most leading cause of cancer related mortality in...

Descripción completa

Detalles Bibliográficos
Autores principales: Bose Nandy, Sushmita, Subramani, Ramadevi, Rajamanickam, Venkatesh, Lopez-Valdez, Rebecca, Arumugam, Arunkumar, Boopalan, Thiyagarajan, Lakshmanaswamy, Rajkumar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4167510/
https://www.ncbi.nlm.nih.gov/pubmed/25176219
http://dx.doi.org/10.1186/1471-2407-14-644
_version_ 1782335431146209280
author Bose Nandy, Sushmita
Subramani, Ramadevi
Rajamanickam, Venkatesh
Lopez-Valdez, Rebecca
Arumugam, Arunkumar
Boopalan, Thiyagarajan
Lakshmanaswamy, Rajkumar
author_facet Bose Nandy, Sushmita
Subramani, Ramadevi
Rajamanickam, Venkatesh
Lopez-Valdez, Rebecca
Arumugam, Arunkumar
Boopalan, Thiyagarajan
Lakshmanaswamy, Rajkumar
author_sort Bose Nandy, Sushmita
collection PubMed
description BACKGROUND: microRNAs have recently succeeded in grabbing the center stage in cancer research for their potential to regulate vital cellular process like cell cycle, stem cell renewal and epithelial mesenchymal transition. Breast cancer is the second most leading cause of cancer related mortality in women. The main reason for mortality is chemoresistance and metastasis for which remnant stem cells are believed to be the cause. One of the natural ways to reduce the risk of breast cancer in women is early pregnancy. Unraveling the mechanism behind it would add to our knowledge and help in evolving newer paradigms for breast cancer prevention. The current study deals with investigating transcriptomic differences in putative stem cells in mammary epithelial cell population (MECs) in terms of genes and microRNAs. In silico tools were used to identify potential mechanisms. ALDH positive MECs represent a putative stem cell population in the mammary gland. METHODS: MECs were extracted from the mammary gland of virgin and parous (one time pregnant) rats. ALDH positive MECs were sorted and used for transcriptional and translational analysis for genes and microRNAs. In silico analysis for target prediction and networking was performed through online portals of Target Scan and Metacore. RESULTS: A total of 35 and 49 genes and microRNAs respectively were found to be differentially expressed within the two groups. Among the important genes were Lifr, Acvr1c, and Pparγ which were found to be targeted by microRNAs in our dataset like miR-143, miR-30, miR-140, miR-27b, miR-125a, miR-128ab, miR-342, miR-26ab, miR-181, miR-150, miR-23ab and miR-425. In silico data mining and networking also demonstrates that genes and microRNA interaction can have profound effects on stem cell renewal, cell cycle dynamics and EMT processes of the MEC population. CONCLUSIONS: Our data clearly shows that certain microRNAs play crucial role in the regulation of ALDH positive MECs and favor an anti-carcinogenic environment in the post-partum gland. Some of the potential interplaying mechanisms in the ALDH positive MEC population identified through this study are p21, Lifr and Pparγ mediated cell cycle regulation, regulation of metastasis and expansion of stem cell pool respectively. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2407-14-644) contains supplementary material, which is available to authorized users.
format Online
Article
Text
id pubmed-4167510
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-41675102014-09-19 microRNA alterations in ALDH positive mammary epithelial cells: a crucial contributing factor towards breast cancer risk reduction in case of early pregnancy Bose Nandy, Sushmita Subramani, Ramadevi Rajamanickam, Venkatesh Lopez-Valdez, Rebecca Arumugam, Arunkumar Boopalan, Thiyagarajan Lakshmanaswamy, Rajkumar BMC Cancer Research Article BACKGROUND: microRNAs have recently succeeded in grabbing the center stage in cancer research for their potential to regulate vital cellular process like cell cycle, stem cell renewal and epithelial mesenchymal transition. Breast cancer is the second most leading cause of cancer related mortality in women. The main reason for mortality is chemoresistance and metastasis for which remnant stem cells are believed to be the cause. One of the natural ways to reduce the risk of breast cancer in women is early pregnancy. Unraveling the mechanism behind it would add to our knowledge and help in evolving newer paradigms for breast cancer prevention. The current study deals with investigating transcriptomic differences in putative stem cells in mammary epithelial cell population (MECs) in terms of genes and microRNAs. In silico tools were used to identify potential mechanisms. ALDH positive MECs represent a putative stem cell population in the mammary gland. METHODS: MECs were extracted from the mammary gland of virgin and parous (one time pregnant) rats. ALDH positive MECs were sorted and used for transcriptional and translational analysis for genes and microRNAs. In silico analysis for target prediction and networking was performed through online portals of Target Scan and Metacore. RESULTS: A total of 35 and 49 genes and microRNAs respectively were found to be differentially expressed within the two groups. Among the important genes were Lifr, Acvr1c, and Pparγ which were found to be targeted by microRNAs in our dataset like miR-143, miR-30, miR-140, miR-27b, miR-125a, miR-128ab, miR-342, miR-26ab, miR-181, miR-150, miR-23ab and miR-425. In silico data mining and networking also demonstrates that genes and microRNA interaction can have profound effects on stem cell renewal, cell cycle dynamics and EMT processes of the MEC population. CONCLUSIONS: Our data clearly shows that certain microRNAs play crucial role in the regulation of ALDH positive MECs and favor an anti-carcinogenic environment in the post-partum gland. Some of the potential interplaying mechanisms in the ALDH positive MEC population identified through this study are p21, Lifr and Pparγ mediated cell cycle regulation, regulation of metastasis and expansion of stem cell pool respectively. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2407-14-644) contains supplementary material, which is available to authorized users. BioMed Central 2014-08-31 /pmc/articles/PMC4167510/ /pubmed/25176219 http://dx.doi.org/10.1186/1471-2407-14-644 Text en © Nandy et al.; licensee BioMed Central Ltd. 2014 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Bose Nandy, Sushmita
Subramani, Ramadevi
Rajamanickam, Venkatesh
Lopez-Valdez, Rebecca
Arumugam, Arunkumar
Boopalan, Thiyagarajan
Lakshmanaswamy, Rajkumar
microRNA alterations in ALDH positive mammary epithelial cells: a crucial contributing factor towards breast cancer risk reduction in case of early pregnancy
title microRNA alterations in ALDH positive mammary epithelial cells: a crucial contributing factor towards breast cancer risk reduction in case of early pregnancy
title_full microRNA alterations in ALDH positive mammary epithelial cells: a crucial contributing factor towards breast cancer risk reduction in case of early pregnancy
title_fullStr microRNA alterations in ALDH positive mammary epithelial cells: a crucial contributing factor towards breast cancer risk reduction in case of early pregnancy
title_full_unstemmed microRNA alterations in ALDH positive mammary epithelial cells: a crucial contributing factor towards breast cancer risk reduction in case of early pregnancy
title_short microRNA alterations in ALDH positive mammary epithelial cells: a crucial contributing factor towards breast cancer risk reduction in case of early pregnancy
title_sort microrna alterations in aldh positive mammary epithelial cells: a crucial contributing factor towards breast cancer risk reduction in case of early pregnancy
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4167510/
https://www.ncbi.nlm.nih.gov/pubmed/25176219
http://dx.doi.org/10.1186/1471-2407-14-644
work_keys_str_mv AT bosenandysushmita micrornaalterationsinaldhpositivemammaryepithelialcellsacrucialcontributingfactortowardsbreastcancerriskreductionincaseofearlypregnancy
AT subramaniramadevi micrornaalterationsinaldhpositivemammaryepithelialcellsacrucialcontributingfactortowardsbreastcancerriskreductionincaseofearlypregnancy
AT rajamanickamvenkatesh micrornaalterationsinaldhpositivemammaryepithelialcellsacrucialcontributingfactortowardsbreastcancerriskreductionincaseofearlypregnancy
AT lopezvaldezrebecca micrornaalterationsinaldhpositivemammaryepithelialcellsacrucialcontributingfactortowardsbreastcancerriskreductionincaseofearlypregnancy
AT arumugamarunkumar micrornaalterationsinaldhpositivemammaryepithelialcellsacrucialcontributingfactortowardsbreastcancerriskreductionincaseofearlypregnancy
AT boopalanthiyagarajan micrornaalterationsinaldhpositivemammaryepithelialcellsacrucialcontributingfactortowardsbreastcancerriskreductionincaseofearlypregnancy
AT lakshmanaswamyrajkumar micrornaalterationsinaldhpositivemammaryepithelialcellsacrucialcontributingfactortowardsbreastcancerriskreductionincaseofearlypregnancy