Madhulika Singh
CSIR-Indian Institute of Toxicology Research, India
Title: Differential miRNAs expression profiles classify Mucin 1(+)/(-) human breast cancer stem cells
Biography
Biography: Madhulika Singh
Abstract
Background: Mucin 1 (Muc1) is a secreted, oncogenic mucin that is aberrantly overexpressed in breast cancer cells but its potential role in breast cancers stem cells (BCSCs) have not been explored. MicroRNAs (miRNA), small noncoding RNAs that play critical roles in normal stem cell functions during development, have emerged as important regulators of BCSCs as well.
Methods: Muc positive (+)/(-) cells were isolated from patient-derived cancer (n=25), and normal BC tissues (n=15) and propagated in non-adhesive suspension cell culture to assess their phenotypic characteristics. Further miRNAs expression profiling was done by using microRNA TaqMan® Low Density Array Cards v2.0 (TLDA cards A, Invitrogen), based on qReal-Time PCR array.
Results: Significantly altered expression of miRNAs were found (17 upregulated and 29 down regulated) in Muc (+) BCSCs as compared to Muc(-) (p<0.05). All these miRNAs were having significant role in BCSCs self-renewal, proliferation potential and were also involved in cancer metastasis. Further, selected miRNAs expression levels were individually tested and validated in mammospheres generated from tissue samples. Muc(+) BCSCs were showing higher level of miRNAs -9, 16, 34a, 195-5p and 454 as compared to Muc(-) BCSCs. Significantly downregulated expression of miR-106a, 125b and 218 was also noted in Muc (+) BCSCs as compared to adhered and Muc(-) cell population.
Conclusions: These miRNAs can potentially be used to develop a panel for classification and prognosis in order to better predict the progression of the disease and facilitate the choice of treatment strategy.