Circular RNA hsa_circ_0001666 sponges miR‑330‑5p, miR‑193a‑5p and miR‑326, and promotes papillary thyroid carcinoma progression via upregulation of ETV4

Qi,Ying; He,Jingni; Zhang,Ying; Wang,Lidong; Yu,Yifan; Yao,Baiyu; Tian,Zhong

doi:10.3892/or.2021.8001

Circular RNA hsa_circ_0001666 sponges miR‑330‑5p, miR‑193a‑5p and miR‑326, and promotes papillary thyroid carcinoma progression via upregulation of ETV4

Authors:
- Ying Qi
- Jingni He
- Ying Zhang
- Lidong Wang
- Yifan Yu
- Baiyu Yao
- Zhong Tian
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Affiliations: Department of Radiology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110022, P.R. China, Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110022, P.R. China, Department of Clinical Oncology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110022, P.R. China
Published online on: March 3, 2021 https://doi.org/10.3892/or.2021.8001
Article Number: 50
Copyright: © Qi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Circular RNAs (circRNAs) are a group of regulators that affect the aggressive behaviors of several types of cancer. Hsa_circ_0001666 (also referred to as hsa_circ_000742) is a newly discovered circRNA that is upregulated in human papillary thyroid carcinoma (PTC) based on microarray analysis. However, the role of hsa_circ_0001666 in PTC progression remains unknown. Thus, the aim of the present study was to determine the potential function and underlying mechanism of hsa_circ_0001666 in PTC. The results demonstrated that hsa_circ_0001666 was upregulated in both PTC clinical samples and cell lines. Its expression was associated with lymph node metastasis of patients with PTC. Knocking down hsa_circ_0001666 expression inhibited cell proliferation, as evidenced by decreased cell viability, arrest of cell cycle progression at the G₁ phase and an increase in cell cycle‑associated proteins. Apoptosis rates and expression levels of pro‑apoptotic proteins were also increased by silencing hsa_circ_0001666. In xenograft experiments, the oncogenic effect of hsa_circ_0001666 on tumor growth was verified. Additionally, luciferase reporter assays showed that hsa_circ_0001666 and ETS variant transcription factor 4 (ETV4) shared common binding sites with three microRNAs [(miRNA/miR)‑330‑5p, miR‑193a‑5p and miR‑326]. Knockdown of these miRNAs separately reversed the inhibitory effect of hsa_circ_0001666 small interfering RNAs on PTC tumor aggressiveness, and ETV4 overexpression also induced a similar effect to that of miRNA inhibitors. Thus, hsa_circ_0001666 may function as an oncogene, promoting PTC tumorigenesis via the miR‑330‑5p/miR‑193a‑5p/miR‑326/ETV4 pathway. This provides a basis for identifying potential novel therapeutic targets for PTC.

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