Abstract 748: Role of LINC01614 in papillary thyroid cancer

Abstract

Abstract Papillary thyroid cancer (PTC) accounts for the vast majority of thyroid cancer cases (~80%), with a significantly higher prevalence in females, but much more aggressive and with poorer outcomes in males. Despite a high survival rate, disease recurrence and metastasis remain significant issues. Therefore, there is an unmet need for the elucidation and identification of molecular markers associated with PTC, to aid in identifying early-stage disease, as well as patient prognosis and therapeutic approaches. Long intergenic non-coding RNA (lincRNA) molecules comprise the largest subclass of RNA molecules within the human genome, yet the majority of their functions are yet to be identified. Evidence supports that these non-coding RNA molecules play a role in protein and RNA localization and scaffolding - implying a critical role in the fine tuning of gene expression. Recently, lincRNAs have been identified as major players in cancer development and progression. This deems lincRNAs as attractive, specific biomarkers and/or therapeutic targets, making them important aspects for further study. Data from our lab identified LINC01614 as being significantly upregulated (~10-fold increase) in PTC, when compared to normal thyroid tissue. There was also ~30-fold increase in LINC01614 in male PTC when compared to females, highlighting potential sex-related correlation for study. Thus, we are studying LINC01614 as a potential biomarker for diagnosis and prognosis, as well as a target for therapeutic intervention. LINC01614 was found to be upregulated in various thyroid cancer cell lines, with significant upregulation in the TPC1 (~5-fold; RET/PTC rearrangement) and K1 (~2-fold; BRAFV600E) cell lines when compared to the “normal”, immortalized thyroid cancer cell line (Nthy-ori-3-1). To decipher a phenotype for LINC01614 upregulation in PTC, we utilized the CRISPRi technique to decrease its expression in TPC1. The knockdown of LINC01614 resulted in a ~75% reduction in proliferation in TPC1 cells. Studies are underway to investigate the role of LINC01614 in migration, invasion, morphology, and tumorigenicity in TPC1 cells, as well as in the BRAFV600E cells, K1. Exploring the role that lincRNAs have in cancer phenotypes can lead to a plethora of different molecular markers for therapeutic intervention. The mechanisms by which these non-coding molecules regulate the expression of genes and other elements of the cellular milieu can serve as an open revenue for understanding how they impact PTC development and progression. Citation Format: Danielle Quaranto, Michelle Carnazza, Nicole DeSouza, Sina Dadafarin, Augustine Moscatello, Raj K. Tiwari, Jan Geliebter. Role of LINC01614 in papillary thyroid cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 748.