Andrea Kasinski, PhD

While various mechanisms contribute to lung cancer, loss of a type of tumor-suppressing molecules called microRNAs is one that specifically gives lung cancer cells a competitive advantage. Based on this knowledge, which was uncovered over two decades ago, approaches to understand the mechanisms that drive global microRNA loss have been under intense investigation. We recently identified a mechanism that can explain this loss. We will validate this mechanism, which we hypothesize lung cancer cells use to rid themselves of large subsets of microRNAs. If supported, we will answer a question that has been plaguing the lung cancer field for decades–how do lung cancer cells rid themselves of a major cohort of tumor-suppressive microRNAs? And, through identifying the mechanism, we will be poised to evaluate interventions that could prevent microRNA loss, leading to demise of the cancer. 

Update:

Our research discovered that certain microRNAs in tumor cells are transported out of the cells if they have a particular five-nucleotide sequence. We found that this sequence is essential and complete for this export process in non-small cell lung cancer (NSCLC) cells, but not in normal bronchial cells. This strongly indicates that NSCLC cells cannot retain these microRNAs, which likely benefits the cancer both internally and externally. Our main goal for the upcoming funding period is to discover the factors responsible for this new effect, manipulate these factors, and see how NSCLC responds. By the end of this funding year, we aim to reveal how NSCLC cells use a mechanism to release microRNAs that suppress tumors and affect the immune system, benefiting the tumor both inside and outside the cells.