Jan-Jong Hung
National Cheng Kung University
Taiwan
Title: Role of Ubiquitination in Lung Cancer Progression
Biography
Biography: Jan-Jong Hung
Abstract
rnUbiquitin is a critical modifier that regulates the degradation and function of its target protein during post-translational modification. In this study, we found that USP24 is higher expressed in the Cell lines with more malignancy and lung cancer clinical samples of late stage. Studying the single Nucleotide polymorphism of USP24 using genomic DNA of lung cancer patients found an increase in the SNP at 7656C→T. Instead of genomic DNA, using RNA specimens of lung cancer patients to Study the SNP of USP24 appeared that significant increase the ratio of the variant in the 930C→T and 7656T→C compared to the ratio found in the genomic DNA, suggesting that the variant at these two sites is not only found in genomic level but in the process of RNA editing. USP24-930T and USP24-7656C increases expressed level through increasing their RNA stability. Knocking down the level of USP24 increased SUV39h1 level through a decrease in the MDM2 level, thus increased lysine 9 methylation of histone-H3 resulted in preventing lung cancer malignancy. Finally, to study the SNP of USP24 using blood specimen of lung cancer patients also found a higher ratio variant compared to normal population, indicating that the SNP of USP24 at 930C→T and 7656T→C might be as a diagnostic marker for cancer detection. Recently we also found that several cancer-related proteins (Bax, p300, E2F4, TFDP1 and securing) have been proven to be Substrates of USP24 and relevance has been shown between USP24 and its substrates in samples from clinical lung cancer patients. Silencing USP24 increases the cancer formation by inhibiting Cellular apoptosis and increasing cellular proliferation. The molecular mechanism involves a decrease in the USP24 level, which reduces the expression of E2F4 and its partner TFDP1 and thus Increases the G1/S transition. The decrease of USP24 in mitosis also reduces the securing level and Promotes separate activation, thereby facilitating the metaphase-anaphase transition. In conclusion, The USP24 level was decreased during the early stage of cancer and the mitotic stage of the cell Cycle to regulate its substrates p300, Bax, E2F4, and securing, resulting in decreased cell apoptosis and increased cell cycle progression and, thus, cancer formation.rn