Date of Award
5-24-2022
Document Type
Master's Thesis - Restricted (NYMC/Touro only) Access
Degree Name
Master of Science
Department
Biochemistry and Molecular Biology
First Advisor
Dr. Jan Geliebter, Ph.D.
Second Advisor
Dr. Raj Tiwari, Ph.D.
Third Advisor
Dr. Joseph Wu, Ph.D.
Abstract
Papillary thyroid cancer (PTC) accounts for the 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. The elucidation and identification of molecular markers associated with PTC remains a prominent unmet need. Identification of these markers could aid in identifying early- stage disease, as well as patient prognosis, therapeutic approaches, and patient outcomes. 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 the regulation of gene expression, and have recently been identified as major players in cancer development and progression when aberrantly expressed. This deems lincRNAs as potential biomarkers and/or therapeutic targets, making them important for further study. Data from our lab identified LINC01614 as being significantly upregulated (~12-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, this thesis focuses on the beginning study of LINC01614 as a potential biomarker for diagnosis and prognosis, as well as a target for therapeutic intervention. To develop our cellular model, LINC01614 was found to be upregulated in thyroid cancer cell line TPC1 (~5-fold) 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 reduction in proliferation, migration, clonogenicity, and cell viability in TPC1 cells. 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 avenue for understanding how they impact PTC development and progression.
Recommended Citation
Quaranto, Danielle, "Role of LINC01614 in Papillary Thyroid Cancer" (2022). NYMC Student Theses and Dissertations. 35.
https://touroscholar.touro.edu/nymc_students_theses/35
