Microrna, signaling, and hormones
MicroRNAs (miRNAs) are small non-coding 18-22 long RNAs, which act as key mediators in many cellular processes involved in tumorigenesis including proliferation, differentiation, invasion, and apoptosis. miRNAs repress gene expression by inhibiting mRNA translation or by promoting mRNA degradation. Due to the importance of miRNAs as master regulators of gene expression many studies have emerged to distinguish both miRNA targets and regulatory mechanisms governing miRNA translation and maturation. Uncovering mechanisms that govern miRNA expression and function in cellular biology gives greater insight into pathways facilitating multiple cellular processes involved in tumor initiation and progression. miRNAs are altered in breast cancer and these alterations can lead to changes in signaling pathways involved in cancer progression. The purpose of this work is to determine the effects of miRNA expression on the cancer phenotype and to examine the roles of insulin-like growth factor 1 (IGF-1) and estrogen receptor (ER) signaling on miRNA expression and function in ER+ breast cancer cell systems. Our results demonstrate the intricate relationship between miRNAs and cell signaling networks. Through uncovering miRNA regulating networks such as IGF-1 signaling and ER induced miRNA maturation and star strand selection we have added greater insight to the complex mechanisms involved in miRNA function. miRNAs function through inhibition of mRNA targets, though the possible targets for a single miRNA can be in the thousands. Additionally, mRNA isoform variability and loss of 3’UTR greatly enhance the complexity of these networks.