Simultaneous Expression of Long Non-Coding RNA FAL1 and Extracellular Matrix Protein 1 Defines Tumour Behaviour in Young Patients with Papillary Thyroid Cancer.

Seonhyang Jeong,Gibbeum Lee,Sunmi Park,Hyunji Kim,Seul-Gi Lee,Young-Suk Jo,In-Kyu Kim,Jandee Lee

doi:10.3390/cancers13133223

Seonhyang Jeong, Gibbeum Lee + Show 6 more

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https://doi.org/10.3390/cancers13133223

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Journal: Cancers	Publication Date: Jun 28, 2021
Citations: 5	License type: CC BY 4.0

Affiliation: Yonsei University, Severance Hospital, Eulji University

Abstract

Simple SummaryFAL1 upregulation has been reported in many types of human cancers. The up-regulatory mechanism was identified in ovarian cancer but was not investigated in other type of cancers. Using The Cancer Genome Atlas (TCGA) database, we identified simultaneous upregulation of FAL1 adjacent to chromosome 1q21.3. Among 53 putative transcription factors for FAL1 and neighbouring genes, we selected c-JUN and JUND as the best candidates. This simultaneous upregulation defines molecular biological features representing RAS-driven PTC-enriched immune-related gene sets. These findings suggest that the simultaneous upregulation might be a potential diagnostic and therapeutic target for RAS-driven PTC.We investigated the regulatory mechanism of FAL1 and unravelled the molecular biological features of FAL1 upregulation in papillary thyroid cancer (PTC). Correlation analyses of FAL1 and neighbouring genes adjacent to chromosome 1q21.3 were performed. Focal amplification was performed using data from copy number alterations in The Cancer Genome Atlas (TCGA) database. To identify putative transcriptional factors, PROMO and the Encyclopaedia of DNA Elements (ENCODE) were used. To validate c-JUN and JUND as master transcription factors for FAL1 and ECM1, gene set enrichment analysis was performed according to FAL1 and ECM1 expression. Statistical analyses of the molecular biological features of FAL1- and ECM1-upregulated PTCs were conducted. FAL1 expression significantly correlated with that of neighbouring genes. Focal amplification of chromosome 1q21.3 was observed in ovarian cancer but not in thyroid carcinoma. However, PROMO suggested 53 transcription factors as putative common transcriptional factors for FAL1 and ECM1 simultaneously. Among them, we selected c-JUN and JUND as the best candidates based on ENCODE results. The expression of target genes of JUND simultaneously increased in FAL1- and ECM1-upregulated PTCs, especially in young patients. The molecular biological features represented RAS-driven PTC and simultaneously enriched immune-related gene sets. FAL1 and ECM1 expression frequently increased simultaneously and could be operated by JUND. The simultaneous upregulation might be a potential diagnostic and therapeutic target for RAS-driven PTC.

Highlights

Papillary thyroid cancer (PTC) is the most common endocrine malignancy, and its incidence has been increasing worldwide [1,2]
We investigated the mechanism underlying FAL1 upregulation in PTC and found that extracellular matrix protein 1 (ECM1) expression was simultaneously upregulated with FAL1 expression
Upregulation of FAL1 expression was first reported in ovarian cancer

Summary

Introduction

Papillary thyroid cancer (PTC) is the most common endocrine malignancy, and its incidence has been increasing worldwide [1,2]. The main reason for this increase has been attributed to the widespread application of highly sensitive ultrasound to health screenings [3]. In this context, a new approach called active surveillance is being widely studied in the clinical setting [4]. Basic experiments and clinical studies on thyroid cancer occurring in young patients and refractory thyroid cancer relatively commonly observed in the elderly are being conducted [5,6,7,8] These efforts have led to the development of various tyrosine kinase inhibitors, including targeted therapy for BRAFV600E, for the clinical setting. No new emerging therapeutic targets have been suggested [9]

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