miRNA profiling reveals a potential role of milk stasis in breast carcinogenesis

: The tumor microenvironment plays an important role in breast carcinogenesis. Milk acts as an important microenvironment of breast cancer, but its role in breast carcinogenesis is largely unknown. Milk stasis may exist in the breast for a number of years after breastfeeding. In the present study, we reported the first microRNA (miRNA) profiling of milk from patients with milk stasis. We identified 266 known miRNAs and 271 novel miRNAs in 10 milk stasis only samples, 271 known miRNAs and 140 novel miRNAs in 10 milk stasis plus breast neoplasm samples by deep sequencing. miRNA profiles were different between the two groups. Furthermore, nine tumor suppressor miRNAs such as miR-29a, miR-146 and miR-223 were significantly downregulated, while seven oncogenic miRNAs such as miR-451, miR-486, miR-107, miR-92 and miR-10 were significantly upregulated in the milk of milk stasis plus neoplasm patients. Three of the identified miRNAs (miR-140, miR-21 and let-7a) were selected using real-time PCR, confirming that these miRNAs were highly expressed. The results also showed that the three miRNAs detected were more abundant in the milk than in the blood. In summary, the data suggested that miRNAs in milk from milk stasis patients may contribute to breast carcinogenesis and that they are more sensitive biomarkers for breast cancer than miRNAs in the blood.