Coding and Noncoding RNA Determinants of Invasion and Migration in Papillary Thyroid Cancer

Author Type(s)

Faculty

Document Type

Abstract

Publication Date

7-1-2021

DOI

10.1158/1538-7445.AM2021-2254

Journal Title

Cancer Research

Department

Otolaryngology

Second Department

Pathology, Microbiology and Immunology

Abstract

Papillary thyroid cancer (PTC) is now the 8th most common cancer in women in the United States and has been increasing in incidence over the last few decades. While it is often curable, aggressive forms of PTC that are not adequately treated by current therapeutic modalities invade into surrounding tissue, with a poor prognosis. Thus, the identification of genes involved in PTC migration and invasion is an unmet need. Differentially expressed (PTC vs. matched, normal) coding and noncoding genes from our own biobank were ranked, comparing invasive vs noninvasive, and lymph node positive vs lymph node negative samples. This analysis was supplemented with the interrogation s of The Cancer Genome Atlas (TCGA) PTC gene expression database for survival-associated genes (Kaplan Meier survival curves) utilizing the Xena Browser. This meta-analysis identified genes with a significant impact on survival, that correlated with lymph node metastasis and tumor invasion. SPOCK3, a Ca+2-binding proteoglycan protein with metalloendopeptidase activity, with a role in both extracellular matrix (ECM) degradation and ERK signaling, correlated with both invasiveness and lymph node spread. SLC30A3 (Solute Carrier Family 30 Member 3), involved in the accumulation of zinc in synaptic vesicles and the transport of sugars, bile salts, organic acids, metal ions and amine compounds, also correlated with both invasiveness and lymph node spread. COL26A1, was found to be correlated to tumor invasion and codes for collagen type XXVI α1 chain with known roles in degradation of the ECM and collagen chain trimerization. Long noncoding RNAs (lncRNAs) have vast implications in different cancer types with roles in gene expression via modulation of coding and noncoding RNAs, and are cell, tissue and stage-specific. lncRNAs were identified that correlated with differentiation, invasion and lymph node spread. CRISPR guides were designed and introduced into thyroid cancer cell lines and decreased the invasion and migration capacity of the thyroid cancer cells. This implies their potential use as prognostic markers and actionable therapeutic targets for small molecule inhibitors.

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