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INTERNATIONAL CONGRESS OF

CancerGenetics

• Human Milk miRNAs and Cancer: From Early-Life Molecular Programming to Cancer Risk

• Saeedeh Askarian,^1,* Amir Mohammad Davar Panah,² Mohammad Hossein pourakbar ,³
  1. Department of Medical Biotechnology, Neyshabur University of Medical Sciences, Neyshabur, Iran.
  2. Department of Medical Biotechnology, Neyshabur University of Medical Sciences, Neyshabur, Iran.
  3. Department of Medical Biotechnology, Neyshabur University of Medical Sciences, Neyshabur, Iran.
  
  
  
• Introduction: MicroRNAs (miRNAs) are small (21–23 nucleotides), endogenously produced non coding RNAs that regulate gene expression at the post transcriptional level and influence proliferation, differentiation, apoptosis, immune responses, tissue development, and cellular homeostasis. Their expression is constantly changing and alters with developmental stage, tissue type, physiological state and environmental conditions. MiRNAs are found in human milk with diverse miRNAs such as miR-148a, miR-21, miR-200 family, miR-29, miR-146a, miR-155 and let-7, suggesting that early childhood is a crucial stage for contact with regulatory RNA signals. An emerging question is whether miRNA function should be interpreted independently of the life stage in which it is expressed. A miRNA involved in physiological development can be involved in carcinogenesis, tumor progression, metastasis or treatment resistance when dysregulated later in life. Thus, classifying miRNAs as “oncogenic” or “tumor suppressive” may be an oversimplification.
• Methods: This narrative literature review integrated evidence from three areas: (1) miRNAs detected during early life, particularly in human milk; (2) their developmental, epithelial, immune, and epigenetic functions; and (3) original cancer studies investigating the expression, biological functions, and clinical significance of the same miRNAs in adult malignancies. PubMed/MEDLINE and biomedical databases were searched using combinations of terms related to miRNAs, human milk, development, aging, cancer, tumor stage, and prognosis. Evidence was interpreted according to four dimensions: developmental timing, patient age, tumor stage, and cellular/tissue context.
• Results: Frequently expressed miRNAs in human milk are associated with developmental, epithelial, immune and epigenetic pathways including miR-148a, miR-21, miR-200 family members, miR-29, miR-146a, miR-155 and let-7. Some miRNAs displayed significant changes during lactation, suggesting temporally designed exposure in early development. The roles of miR-148a, miR-200c and miR-21 are context-dependent over the life course. miR-148a is involved in intestinal epithelial development and barrier-related processes . Downregulation of miR-148a has been linked to DNMT1 regulation, DNA methylation, proliferation, apoptosis, and tumor progression in gastric and colorectal cancers . MiR-200c is known to play a role in cancer in epithelial differentiation and identity, but also in epithelial-mesenchymal transition, invasion, metastasis and treatment response. Differences in miR-200c expression according to tumor status and age of cancer onset also suggest age-dependent biological interpretation. miR-21 is found in human milk and has an immunoregulatory role, but is often oncogenic in adult cancers and has been associated with advanced disease, lymph-node metastasis, poor prognosis, and decreased survival. Comparative cancer population studies on patient age and tumor stage reveal that miRNA expression and clinical significance can be altered, which may affect diagnostic and prognostic performance.
• Conclusion: The findings suggested a life-course model of miRNAs in our biology. Our early years miRNAs may have a role in influencing our development and immune response but as we age and face challenges with diseases such as cancer their roles can change radically. Thus, the age of the patient and the biological stage of life are important aspects to be considered in the study of miRNA when considering cancer, and not only as additional details. Therefore, by considering patient age, developmental phases, tumor stage, molecular subtypes, and the surrounding cellular environment, we can gain better insights and avoid the trap of labeling miRNAs too simply as either oncogenic or tumor suppressive. This encourages us to reframe our inquiry from “Which miRNA is associated to this cancer?” to a more nuanced exploration of “When, where, and under what biological conditions does this miRNA play in relation to cancer?”
• Keywords: MicroRNAs , Milk, Human , Neoplasms , Carcinogenesis , Aging