MicroRNAs: A Link between Mammary Gland Development and Breast Cancer

Abstract

Breast cancer is among the most common cancers in women, second to skin cancer. Mammary gland development can influence breast cancer development in later life. Processes such as proliferation, invasion, and migration during mammary gland development can often mirror processes found in breast cancer. MicroRNAs (miRNAs), small, non-coding RNAs, can repress post-transcriptional RNA expression and can regulate up to 80% of all genes. Expression of miRNAs play a key role in mammary gland development, and aberrant expression can initiate or promote breast cancer. Here, we review the role of miRNAs in mammary development and breast cancer, and potential parallel roles. A total of 32 miRNAs were found to be expressed in both mammary gland development and breast cancer. These miRNAs are involved in proliferation, metastasis, invasion, and apoptosis in both processes. Some miRNAs were found to have contradictory roles, possibly due to their ability to target many genes at once. Investigation of miRNAs and their role in mammary gland development may inform about their role in breast cancer. In particular, by studying miRNA in development, mechanisms and potential targets for breast cancer treatment may be elucidated.

Cecal microbiota and mammary gland microRNA signatures are related and modifiable by dietary flaxseed with implications for breast cancer risk

“…TEBs are the most likely site for mammary tumors to develop, indicating a potential role of this pathway in pubertal development and cancer risk in later life. This pathway is activated in puberty and dysregulated in breast cancer ( 21 ). The PI3K-Akt-mTOR pathway has also been shown to play a role in breast cancer therapy resistance, with inhibition of mTOR resulting in restored sensitivity to tamoxifen ( 31 ).…”

“…These differences warrant further study into the mechanism of difference between FS and its components, not only in fiber but also in protein. In mice fed the FS diet, protein processing functions were enriched in the microbiome ( 4 ); FS protein may have antioxidant properties and cardiovascular benefits ( 21 ). FS fiber, which includes both soluble and insoluble fiber, can slow FS transit through the gastrointestinal tract, potentially increasing the absorption time of the lignan and oil components.…”

“…Modulation of miRNA expression may be a mechanism underlying host response to metabolic signals, including those generated from microbial metabolites. We recently showed that developmental patterns of mammary gland miRNAs may provide clues to their dysregulated role in breast cancer ( 21 ). Here, we determined if the mammary gland miRNome and the gut microbiota are related, if this relationship is modified by dietary FS, and if FS-associated miRNAs are altered in human breast cancer.…”

Metformin and Breast Cancer: Current Findings and Future Perspectives from Preclinical and Clinical Studies

“…miRNAs are short non-coding RNAs that are 17–25 nucleotides that are evolutionarily conserved, while lncRNAs have a length of >200 nucleotides [ 55 ]. Dysregulation of miRNAs in cancer has been associated with EMT, invasion, migration, proliferation, and other negative consequences [ 56 ]. Similarly, research indicates that lncRNAs are integral players in various phases of cancer initiation and progression [ 55 , 57 , 58 ].…”

“…In the context of breast cancer, they can act as promoters or inhibitors of invasion and metastasis [ 58 ]. The role of miRNAs and lncRNAs in breast cancer have been reviewed elsewhere [ 55 , 56 , 58 , 59 , 60 ]; here, we summarize the main findings of how metformin modulation of RNAs can impact breast cancer outcomes.…”