Alternative regulation of MYC in lung cancer
Lung cancer is the leading cause of cancer deaths in the United States, accounting for 27% of all cancer induced deaths1. In an attempt to create a effective targeted therapy for the treatment of lung cancer, a strategy used to treat an activated KrasG12D/+;p53 R172H/+ transgenic lung cancer mouse model was to deliver a known tumor suppressive microRNA (miRNA) to stop tumor growth. The tumor suppressive miRNA let-7 was lentivirally delivered in the form of its primary transcript, pri-let-7a-1, and resulted in increased lung size and inflammation compared to lungs exposed to a control lentivirus. It was identified that LIN28B transcripts were elevated in this transgenic model2 and a truncated MYC protein product, separate from canonical MYC, was overexpressed with activation of the transgenic lung cancer mouse model. LIN28B is a pluripotent factor and post-transcriptional inhibitor of let-7 biogenesis 3–5. Therefore, it was hypothesized that the LIN28B mediated accumulation of pri-let-7a-1 transcripts promoted expression of the truncated MYC protein product, termed T-MYC. Through this work, it was determined that T-MYC expression is not dependent on the LIN28B mediated accumulation of pri-let-7a-1 transcripts and that T-MYC is likely not a variant of canonical MYC.^
Andrea Kasinski, Purdue University.