Abstract 1406: Long non-coding RNA DUXAP10 is a putative determinant of anaplastic thyroid cancer

Abstract

Abstract Anaplastic Thyroid Cancer (ATC) is one of the most aggressive forms of cancer, with only a 4% survival rate with metastatic disease. ATC is highly refractory and resistant to both traditional therapeutic modalities and recently discovered small molecule inhibitors. The elucidation of molecular mechanisms that contribute to ATC’s metastatic propensity, and the identification of molecular biomarkers for early diagnosis, prognosis, and therapeutic intervention are critical unmet clinical needs-highlighting the importance of novel avenues of intervention. Recently, long non-coding RNAs (lncRNA) have been described as regulators of gene expression and cancer cell phenotypes, exhibiting the importance of identifying non-coding profiles that potentially impact ATC behavior. Publicly available datasets provided by Gene Expression Omnibus (GSE33630, GSE85457) enabled investigation of gene expression profiles of ATC vs. normal thyroid patient tissue. Bioinformatic analyses with the GEO2R program identified the lncRNA, Double Homeobox A Pseudogene 10 (DUXAP10), to be highly upregulated in ATC patient-derived tissue samples when compared to normal thyroid tissue by about 5logFC. Analysis using Gene Expression Profiling Interactive Analysis shows that high DUXAP10 expression is correlated with decreased survival in thyroid cancer patients. To recapitulate this patient data in an in vitro model, we found that the expression of DUXAP10 is also upregulated in the ATC cell line, T238, in comparison to Nthy-ori-3-1, an immortalized “normal” thyroid cell line. To understand the consequences of DUXAP10 overexpression in ATC, we used CRISPRi technology to determine the phenotypic and genotypic effects of DUXAP10 downregulation. CRISPRi knockdown of DUXAP10 significantly reduces the migratory capabilities of T238 by 50%, invasiveness by 37%, clonogenicity by 70%, cell size by 34%, and proliferation by 28%, 45%, and 36% at 24, 48, and 72 hours, respectively. This provides evidence that elevated DUXAP10 expression may increase the probability and negative consequences of metastases. Thus, targeting DUXAP10 expression may have beneficial clinical outcomes. Identification of the molecular innervations of DUXAP10 that orchestrate these pro-metastatic phenotypic changes are currently in progress. Immediate next steps are aimed toward determining if DUXAP10 can be utilized as a potential biomarker for ATC diagnosis and prognosis, as well as elucidating the full range of interactions that DUXAP10 has in shaping the ATC phenotype. Citation Format: Nicole R. DeSouza, Michelle Carnazza, Danielle Quaranto, Tara Jarboe, Kaci Kopec, Sarnath Singh, Augustine Moscatello, Jan Geliebter, Raj K. Tiwari. Long non-coding RNA DUXAP10 is a putative determinant of anaplastic thyroid cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1406.