Graduation Year
2020
Document Type
Dissertation
Degree
Ph.D.
Degree Name
Doctor of Philosophy (Ph.D.)
Degree Granting Department
Biology (Cell Biology, Microbiology, Molecular Biology)
Major Professor
Charles Chalfant, Ph.D.
Co-Major Professor
Margaret Park, Ph.D.
Committee Member
Florian Karreth, Ph.D.
Committee Member
Huzefa Dungrawala, Ph.D.
Keywords
Alternative Splicing, CDKN2A, LncRNA, Lung Cancer
Abstract
Non-small cell lung cancer (NSCLC) is the leading cause of cancer death worldwide with a low 5-year survival rate of only around 21%. This low 5-year survival rate is due to two main reasons. First, NSCLC is often diagnosed at the later stages when it has already metastasized. Second, NSCLC is an incredibly diverse, heterogenous disease making it very hard to target the true molecular oncogenic drivers. New targets for personalized therapeutics are needed based on the expression status of each individual lung cancer tumor.
One way of looking for these new therapeutics is to begin by identifying the oncogenotype status. Two common oncogenotypes in NSCLC which are considered non-actionable, or non-targetable, are mutations in the KRAS or TP53 genes. To target these genotypes, we used transcriptomics and bioinformatics to analyze NSCLC cell lines based on their KRAS or TP53 oncogenotype status for potential alternative splicing events identified via differential exon usage.
Further investigation into these differentially regulated alternatively spliced genes revealed a novel intergenic non-coding RNA which is dysregulated in some NSCLC cell lines. While the precise mechanism behind CDLINC’s CDKN2A dysregulation mechanism is unknown, our data strongly suggest that it is acting as ceRNA to sponge miRNAs thus indirectly suppressing CDKN2A expression. Future directions for this research include identifying CDLINC binding partners and clarifying the mechanisms responsible for its cancer-linked function. In conclusion, the targetability of CDLINC by RNAi suggests it may act as a candidate for targeted therapeutics in the future of NSCLC treatment.
Scholar Commons Citation
Moss, Christina J., "Novel Long Non-Coding RNA CDLINC Promotes NSCLC Progression" (2020). USF Tampa Graduate Theses and Dissertations.
https://digitalcommons.usf.edu/etd/9035
