To Characterize the Role of Ubiquitin-Specific Peptidase 24 in Lung Cancer Metastasis

• Main Authors: Ping-HsinChen, 陳秉鑫
• Other Authors: Jan-Jong Hung
• Format: Others
• Language: zh-TW
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/02147333539140467933

碩士 === 國立成功大學 === 藥理學研究所 === 102 === Lung cancer, the most common cause of cancer-related death worldwide, is a heterogeneous tumor displaying a complex variety of genetic and epigenetic alterations. Single nucleotide polymorphisms (SNPs) are the most common type of human genetic variation. Herein, we have characterized two of the SNPs in Ubiquitin-Specific Peptidases 24 (USP24) gene, rs1165222 and rs487230 variants in lung cancer. Both of them are located on protein coding sequence and resulted in an amino acid change. We conducted a case-control study in a cohort of 100 lung cancer patients and 97 normal populations. The results showed that the rs487230 of SNPs might be associated with lung cancer malignancy. Moreover, the RNA editing-like phenomenon was observed. Interesting, it is preferred to express the USP24Thr226 and Val2468 protein in lung cancer patients. Compared with wild-type USP24 protein, the edited form has not only increased in its protein level but also enhanced its downstream effect. Overexpression of USP24 decreased histone H3 lysine 9 (H3K9) methylation. The protein expression of H3K9 methyltransferase, Suv39H1, was also significantly decreased. It is well known that H3K9 methylation is important for silencing gene expression. Further, we found that metastasis-related genes, CCL5 and ADAM10, were downregulated upon USP24 depletion via H3K9 hypermethylation on the promoters. Both in vivo and in vitro experiments point out that USP24 depletion inhibits cancer metastatic activity. Taken together, USP24 might facilitate lung cancer metastasis via Suv39H1-mediated decrease in H3K9 methylation and subsequent increase in metastasis-promoting genes expression.