CircRNA circTIAM1 promotes papillary thyroid cancer progression through the miR-646/HNRNPA1 signaling pathway

Deguang Zhang,Qinghu Tang,Jianle Wang,Nizheng Xu,Li Tao,Kangmao Huang,Shuying Shen,Gaofei He,Xiaoxiao Lu,Junjie Chu

doi:10.1038/s41420-021-00798-1

Deguang Zhang, Qinghu Tang + Show 8 more

Open Access

https://doi.org/10.1038/s41420-021-00798-1

Copy DOI

Abstract

Papillary thyroid cancer (PTC) is a common endocrine tumor with a rapidly increasing incidence in recent years. Although the majority of PTCs are relatively indolent and have a good prognosis, a certain proportion is highly aggressive with lymphatic metastasis, iodine resistance, and easy recurrence. Circular RNAs (circRNAs) are a class of noncoding RNAs that are linked to a variety of tumor processes in several cancers, including PTC. In the current study, circRNA high-throughput sequencing was performed to identify alterations in circRNA expression levels in PTC tissues. circTIAM1 was then selected because of its increased expression in PTC and association with apoptosis, proliferation, and migration of PTC cells in vitro and in vivo. Mechanistically, circTIAM1 acted as a sponge of microRNA-646 and functioned in PTC by targeting miR-646 and heterogeneous ribonucleoprotein A1. Fluorescence in situ hybridization and dual-luciferase reporter assays further confirmed these connections. Overall, our results reveal an important oncogenic role of circTIAM1 in PTC and may represent a potentially therapeutic target against PTC progression.

Highlights

Thyroid cancer is the most prevalent malignant tumor of the endocrine system and has received increasing attention from researchers owing to its rapidly increasing incidence [1]
A detailed list of the top 50 differentially expressed circRNAs is provided in Fig. S1B and hsa_circ_0061406 releaved highest fold-change in the Papillary thyroid carcinoma (PTC) tissues than in the control tissues which indicates that it may play a key role in PTC and is worthy of further research
High levels of TIAM1 have been reported to increase the risk of recurrence of thyroid cancer [22], and the knockdown of TIAM1 significantly inhibited the migration and invasion potential of PTC cells in vitro [23]

Summary

Introduction

Thyroid cancer is the most prevalent malignant tumor of the endocrine system and has received increasing attention from researchers owing to its rapidly increasing incidence [1]. In the past 30 years, the incidence of thyroid cancer has nearly tripled, and the annual rate of increase in new cases has stabilized at approximately 5% [2]. Papillary thyroid carcinoma (PTC) accounts for almost 85% of these cases [3]. It is urgent to understand the underlying mechanism of the progression of PTC and provide more perspectives for exploring novel therapies for thyroid cancer. Numerous studies have revealed the inseparable relationship between circRNAs and various malignant tumors, including glioma, gastric cancer, osteosarcoma, lung cancer, and hepatocellular carcinoma [7, 13,14,15,16]. Several circRNAs were found to be enriched in PTC tissues and affect PTC progression, which highlights the importance of circRNAs in thyroid cancer

Methods

Results

Conclusion