Localization and Mechanism of MORT in Human Mammary Epithelial Cell Mortal to Immortal Transition

Abstract

Cancer is quickly becoming the leading cause of death in the United States. Despite research making headway with early detection techniques and effective treatments, the number of cancer deaths per year continues to increase. There is still a lot we do not know about the mechanisms of cancer initiation and progression. A relatively recent field of study is epigenetics, or changes that occur outside of the DNA sequence. One such change is the expression or depletion of non-coding RNAs (ncRNAs). One type of ncRNA is long non-coding RNAs (lncRNAs), and several studies have linked lncRNA overexpression or downregulation to cancer progression. Mortal Obligate RNA Transcript, or MORT, is a lncRNA that has only recently been studied. Previous reports have shown lower levels of MORT in cancerous cell lines compared to normal cell lines, but very little additional information is known about the means by which it contributes to cancer progression. Our goal was to determine the localization and mechanism of MORT, specifically as it pertained to the mortal (non-tumorigenic) to immortal (tumorigenic) transition of human mammary epithelial cells. We observed that MORT loss occurs even earlier than previously thought, possibly priming the cells to bypass certain barriers necessary for tumorigenesis. MORT also seems to work in a complex with Poly(rC)-Binding Protein 1 (PCBP1) to somehow regulate certain mRNAs. Further, polysome profile analyses of MORT indicate that two populations of MORT exist within the cell; one with monosomes and one with polysomes. These results have important implications for detecting cancer as well as for understanding cancer progression mechanisms, possibly leading us to pursue therapeutic approaches involving MORT and its mechanisms of action.