ARNTL2: a key player in promoting tumor aggressiveness in papillary thyroid cancer.

IF 1.7 4区 医学 Q4 ONCOLOGY Translational cancer research Pub Date : 2025-01-31 Epub Date: 2025-01-23 DOI:10.21037/tcr-24-1205
Qing Zhai, Han Wu, Shiqiang Liu, Yuehong Zhu, Xi Huang, Junfeng Wang
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Abstract

Background: The increasing occurrence of thyroid cancer (TC), particularly papillary thyroid cancer (PTC), highlights our need for better diagnostic indicators and new therapeutic targets. Aryl hydrocarbon receptor nuclear translocator-like 2 (ARNTL2) plays a crucial function in multiple tumor types. Accordingly, we investigated the oncogenic function and molecular pathways associated with ARNTL2 in PTC.

Methods: Our study utilized the The Cancer Genome Atlas (TCGA) database to examine ARNTL2 expression, which was subsequently confirmed in PTC tissues and cell lines employing quantitative real-time polymerase chain reaction (qRT-PCR) and western blot (WB) analysis. Herein, we evaluated PTC cell proliferation, cell cycle progression, apoptosis, migration, and invasion through Cell Counting Kit-8 (CCK-8), flow cytometry, wound-healing assay, and Transwell assay. Eventually, we determined the mechanism behind ARNTL2 in PTC via WB.

Results: In PTC, a significant ARNTL2 upregulation was observed, which exhibited a positive correlation with enhanced tumor aggressiveness. Additionally, knocking down ARNTL2 facilitated apoptosis, besides impeding cell cycle progression, cell proliferation, migration, and invasion, alongside epithelial-mesenchymal transition (EMT) in PTC. However, the outcomes were reversed when ARNTL2 was overexpressed. Enhanced expression of ARNTL2 led to an elevation in phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) phosphorylation within PTC cells, while the administration of alpelisib effectively mitigated the effects induced by upregulated ARNTL2 on EMT, PTC cell proliferation, apoptosis, and invasion.

Conclusions: Elevated ARNTL2 levels enhance PTC proliferation, migration, invasion, and EMT while inhibiting apoptosis through the cell cycle signaling, elucidating its potential as a diagnostic PTC biomarker.

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ARNTL2:在甲状腺乳头状癌中促进肿瘤侵袭的关键参与者。
背景:甲状腺癌(TC),尤其是乳头状甲状腺癌(PTC)的发病率越来越高,迫切需要更好的诊断指标和新的治疗靶点。芳烃受体核易位样2 (ARNTL2)在多种肿瘤类型中发挥重要作用。因此,我们研究了在PTC中与ARNTL2相关的致癌功能和分子途径。方法:本研究利用the Cancer Genome Atlas (TCGA)数据库检测ARNTL2在PTC组织和细胞系中的表达,并采用实时荧光定量聚合酶链反应(quantitative real-time polymerase chain reaction, qRT-PCR)和western blot (WB)分析证实了该表达。在此,我们通过细胞计数试剂盒-8 (CCK-8)、流式细胞术、伤口愈合实验和Transwell实验来评估PTC细胞的增殖、细胞周期进程、凋亡、迁移和侵袭。最终,我们通过WB确定了ARNTL2在PTC中的作用机制。结果:在PTC中,ARNTL2表达显著上调,且与肿瘤侵袭性增强呈正相关。此外,敲低ARNTL2除了阻碍PTC细胞周期进程、细胞增殖、迁移和侵袭以及上皮-间质转化(EMT)外,还会促进细胞凋亡。然而,当ARNTL2过表达时,结果相反。ARNTL2表达增强可导致PTC细胞内PI3K/AKT磷酸化水平升高,而alpelisib可有效减轻ARNTL2表达上调对EMT、PTC细胞增殖、凋亡和侵袭的影响。结论:升高的ARNTL2水平可增强PTC的增殖、迁移、侵袭和EMT,同时通过细胞周期信号传导抑制凋亡,阐明其作为诊断PTC的生物标志物的潜力。
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来源期刊
CiteScore
2.10
自引率
0.00%
发文量
252
期刊介绍: Translational Cancer Research (Transl Cancer Res TCR; Print ISSN: 2218-676X; Online ISSN 2219-6803; http://tcr.amegroups.com/) is an Open Access, peer-reviewed journal, indexed in Science Citation Index Expanded (SCIE). TCR publishes laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer; results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of cancer patients. The focus of TCR is original, peer-reviewed, science-based research that successfully advances clinical medicine toward the goal of improving patients'' quality of life. The editors and an international advisory group of scientists and clinician-scientists as well as other experts will hold TCR articles to the high-quality standards. We accept Original Articles as well as Review Articles, Editorials and Brief Articles.
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