Xuan Qu
Program: Computational and Systems Biology
Current advisor: Ting Wang, PhD
Undergraduate university: Bowdoin College
Research summary
The relationship between p53 and transposable elements (TEs) has been obscure. Comprehensive profiling of TE-derived transcript dynamics under the regulation of p53 provides valuable resources for more clarity in p53’s roles in cancer. In this study, we created three cancer cell lines with p53 genetic status as the only variable and combined long-read RNA-seq and short-read RNA-seq to define TE and TE-derived transcripts’ regulatory dynamics. We identified in total 2,503 transcripts that used TE as potential promoters, among which, 141 to 210 were activated by p53. We found ERVs to be a main driver of potential promoters, followed by LINEs. Epigenomic profiling including chromatin accessibility and DNA methylation provided additional support for active promoter potential for p53 upregulated TE-derived transcripts. Short-term restoration of p53 partially recovered chronic p53-regulated TE-derived transcript profile but gain of function TP53 mutations, R175H and R273H, did not show evidence to act via TE network. Overall, we provide a controlled isogenic cancer cell line system with TP53 mutation status as the only genetic variable, deliver a high confidence TE and TE-derived transcript atlas and comprehensively identify active TE promoters that are direct and indirect targets of p53.
Graduate publications
iang Y, Qu X, Shah NM, Wang T. 2024 Towards targeting transposable elements for cancer therapy. Nat Rev Cancer, 24(2):123-40.
Shah NM, Jang HJ, Liang Y, Maeng JH, Tzeng SC, Wu A, Basri NL, Qu X, Fan C, Li A, Katz B, Li D, Xing X, Evans BS, Wang T. 2023 Pan-cancer analysis identifies tumor-specific antigens derived from transposable elements. Nat Genet, 55(4):631-39.
DeSouza PA, Qu X, Chen H, Patel B, Maher CA, Kim AH. 2021 Long, Noncoding RNA Dysregulation in Glioblastoma. Cancers (Basel), 13(7):1604..
Mahlokozera T, Patel B, Chen H, Desouza P, Qu X, Mao DD, Hafez D, Yang W, Taiwo R, Paturu M, Salehi A, Gujar AD, Dunn GP, Mosammaparast N, Petti AA, Yano H, Kim AH. 2021 Competitive binding of E3 ligases TRIM26 and WWP2 controls SOX2 in glioblastoma. Nat Commun, 12(1):6321.