Authors:

Marissa Walsh

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About Paper:

t°A is a modified nucleotide in tRNAs that has been found to play a significant role in ensuring proper translation of mRNAs into proteins. Specifically, t?A has been found to promote translation of mRNAs starting at the expected AUG start codon site instead of cryptic start codons [1]. Past research has found that t®A expression is amplified in ovarian cancer cells compared to normal, non-cancerous cells. We hypothesize that inhibition of t°A in ovarian cancer cells increases cryptic translation of mRNAs. Thus, we predict that tA inhibition can increase the synthesis of neoantigens, triggering immune system responses that kill ovarian cancer cells with increased efficiency. This project focuses on how t*A inhibition, via t®A biosynthesis enzyme knockout, impacts translation within cisplatin sensitive and resistant ovarian cancer cell lines. We analyzed cell proliferation via a colony formation experiment, and we analyzed global translation via a flow cytometry experiment. We found that cisplatin sensitive PEO1 cells had little change in cell proliferation due to tA inhibition. Alternatively, we found that cisplatin resistant PEO4 cells had a large decrease in cell proliferation due to t®A inhibition. This indicates that cisplatin resistant ovarian cancer cells are more sensitive to t°A inhibition than cisplatin sensitive cells. We also found that global translation in the cisplatin resistant PEO4 cells did not decrease with t°A inhibition. With these results, we believe that cisplatin resistant PEO4 ovarian cancer cells treated with t°A inhibition have reduced proliferation due to altered translation, indicative of increased production of neoantigens, as predicted in our hypothesis. Further investigation will reveal the specific impacts of t°A inhibition, allowing for a clearer understanding of immunotherapeutic applications of t°A inhibition.

Source:

Northwestern University

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Co-authors:

Marissa Walsh