Abstract 4354: Long noncoding RNA DUXAP10 serves as a putative driver of carcinogenic transformation in anaplastic thyroid cancer
Authors: Nicole R. DeSouza, Michelle Carnazza, Danielle Quaranto, Tara Jarboe, Kaci Kopec, Robert Suriano, Kate Nielsen, Augustine Moscatello, Humayun Islam, Jan Geliebter, Raj K. Tiwari
Journal: Cancer Research (2024)

Abstract Anaplastic Thyroid Cancer (ATC) is the most aggressive thyroid cancer subset, with a &amp;lt;4% five-year survival rate. ATC is completely refractory to traditional therapy and newer immunotherapeutic options. Unlike other lethal cancers, ATC has a low mutational burden, warranting the need for a comprehensive study of differential gene expression patterns. Transcriptomic regulators known as long non-coding RNAs (lncRNA) have been described as pivotal orchestrators of gene expression and drivers of carcinogenic patterns. Thus, we present the role of novel lncRNAs in shaping the ATC genotype and phenotype. ​​Publicly available ATC vs. normal thyroid tissue transcriptomic datasets (Gene Expression Omnibus; GSE33630, GSE85457) were investigated to identify genomic transcripts that are differentially expressed in ATC samples using GEO2R. Bioinformatic analysis identified Double Homeobox A Pseudogene 10 (DUXAP10), as a highly upregulated lncRNA in ATC patient tissue samples in both databases (40-fold and 20-fold). Gene Expression Profiling Interactive Analysis statistically correlated high DUXAP10 expression with decreased survival in thyroid cancer patients. DUXAP10 expression was similarly upregulated in ATC cell line, T238, compared to immortalized “normal” thyroid epithelial cell line, Nthy-ori-3-1. Our T238-CRISPRi knockdown model of DUXAP10 was evaluated in vitro to assess consequences of overexpression. CRISPRi knockdown of DUXAP10 in T238 significantly reduced its migratory capabilities by 50%, invasion index by 30%, clonogenicity by 70%, cell viability by 67%, 60%, and 50% at 24, 48, and 72 hours, respectively, proliferation by 28%, 45%, and 36% at 24, 48, and 72 hours, respectively, and global transcription rate by 65%. Further, our DUXAP10-CRISPRi knockdown exhibited a downregulation of N-Cadherin and mediators of beta-catenin signaling- confirming a role in regulatory cross-talk of central carcinogenic pathways. We are currently evaluating proteins and miRNAs bound to and “sponged” by DUXAP10 in vitro utilizing RNA-centric methodology. These data reveal the novelty of DUXAP10, and that its over-expression may increase the negative consequences of ATC metastasis. Thus, we have identified DUXAP10 as a putative determinant for ATC diagnosis, prognosis, and therapeutic targeting. Citation Format: Nicole R. DeSouza, Michelle Carnazza, Danielle Quaranto, Tara Jarboe, Kaci Kopec, Robert Suriano, Kate Nielsen, Augustine Moscatello, Humayun Islam, Jan Geliebter, Raj K. Tiwari. Long noncoding RNA DUXAP10 serves as a putative driver of carcinogenic transformation in anaplastic thyroid cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4354.