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

IF 1.5 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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引用次数: 0

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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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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