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

BMC Cancer

Sushmita Bose Nandy¹  Ramadevi Subramani¹  Venkatesh Rajamanickam¹  Rebecca Lopez-Valdez¹  Arunkumar Arumugam¹  Thiyagarajan Boopalan¹  Rajkumar Lakshmanaswamy¹ 

[1] Department of Biomedical Sciences MSB1, Center of Excellence in Cancer Research, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, 5001 El Paso Drive, El Paso, TX 79905, USA

关键词: microRNAs;    Breast cancer;    ALDH positive MECs;    Pregnancy;   

Others  :  1121146
DOI  :  10.1186/1471-2407-14-644

 received in 2013-11-29, accepted in 2014-08-20,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Nandy et al.; licensee BioMed Central Ltd.

【 图 表 】

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