Abstract 5668: Long non-coding RNA LINC01614 knockdown decreases carcinogenic behavior of papillary thyroid cancer in vitro

Abstract

Abstract Papillary thyroid cancer (PTC) accounts for the vast majority of thyroid cancer cases with increasing incidence over the past few decades. PTC has a significantly higher prevalence in females in their childbearing years. Despite high survival rates, disease recurrence and metastasis remain prominent issues, thus highlighting the critical need for molecular biomarker detection. A newer class of molecular regulators, known as long non-coding RNAs (lncRNAs), have demonstrated differential expression patterns in a multitude of cancers. The largest subclass of these RNA molecules in the human genome consists of long intergenic non-coding RNAs (lincRNAs) with many of their functions yet to be identified. Known functional roles of lncRNAs center on their ability to modulate gene expression and drive carcinogenic behavior, deeming them attractive biomarkers and/or therapeutic targets for study. Bioinformatic analysis of RNA sequencing data from our patient sample biobank identified LINC01614 as being significantly upregulated (~12 fold increase) in PTC, when compared to normal, matched thyroid tissue. Further, it was also upregulated ~30-fold in male PTC compared to ~5.5 fold increase in female PTC, highlighting a potential sex correlation for study. Thus, we are studying LINC01614 as a potential PTC biomarker. Gene expression analysis of LINC01614 in vitro was found to be upregulated in various thyroid cancer cell lines, specifically two PTC cell lines: TPC1 (~5 fold; RET/PTC rearrangement; female) and K1 (~2 fold; BRAFV600E; male) when compared to the immortalized “normal” thyroid cell line (Nthy-ori-3-1). For phenotypic evaluation, we utilized the CRISPRi technique to employ transcriptional repression of LINC01614 in both TPC1 and K1. LINC01614 knockdown in TPC1 and K1 resulted in decreased healing capacity (~20%), clonogenicity (~50% and ~34%, respectively), and proliferation (~55% and ~45%, respectively). Studies are currently underway to further assess invasion, morphology, and RNA localization within the cell in vitro, as well as the identification of potential protein interactions and mechanisms of action of LINC01614 in PTC. Studying lncRNAs and their regulatory roles in cancer cell function is critical in the identification of various diagnostic and prognostic biomarkers for therapeutic intervention. Our data support the potential biological role of LINC01614 in driving PTC growth and metastatic potential. Further elucidation of how LINC01614 impacts PTC development and progression is a promising avenue of exploration. Citation Format: Danielle Quaranto, Michelle Carnazza, Nicole R. DeSouza, Sina Dadafarin, Augustine Moscatello, Humayun K. Islam, Raj K. Tiwari, Jan Geliebter. Long non-coding RNA LINC01614 knockdown decreases carcinogenic behavior of papillary thyroid cancer in vitro [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 5668.