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环状HIPK2通过miR-889-3p/MCTS1/IL-6轴促进喉鳞状细胞癌的恶性进展。

circHIPK2 promotes malignant progression of laryngeal squamous cell carcinoma through the miR-889-3p/MCTS1/IL-6 axis.

作者信息

Sun Yang-Guang, Yu Zhen-Kun, Chen Xi, Zhang Si-Yao, Wu Wan-Juan, Liu Kai, Cheng Lei

机构信息

Department of Otorhinolaryngology, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China.

Nanjing Medical Key Laboratory of Laryngopharynx-Head & Neck Oncology, Department of Otolaryngology-Head and Neck Surgery, BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing 210019, China.

出版信息

Transl Oncol. 2025 Jun;56:102390. doi: 10.1016/j.tranon.2025.102390. Epub 2025 Apr 12.

DOI:10.1016/j.tranon.2025.102390
PMID:40222337
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12018564/
Abstract

Laryngeal squamous cell carcinoma (LSCC) is a common malignant tumor of the head and neck with a poor prognosis. The role of circRNAs in LSCC remains largely unknown. In this study, quantitative real-time PCR (qRT-PCR), Sanger sequencing and fluorescence in situ hybridization were undertaken to detect the expression, localization, and clinical significance of circHIPK2 in LSCC tissues and TU686 and TU212 cells. The functions of circHIPK2 in LSCC were explored through proliferation analysis, EdU staining, colony formation assay, wound healing assay, and Transwell assay. The regulatory mechanisms underpinning circHIPK2, miR-889-3p, and MCTS1 were investigated using luciferase assay, Western blotting, and qRT-PCR. We found that LSCC tissues and cells demonstrated high expression of circHIPK2 that was closely associated with the malignant progression and poor prognosis of LSCC. Knockdown of circHIPK2 inhibited the proliferation and migration of LSCC cells in vitro. Mechanistic studies showed that circHIPK2 competitively bound to miR-889-3p, elevated MCTS1 level, promoted IL-6 secretion, and ultimately accelerated the malignant progression of LSCC. In conclusion, an axis involving circHIPK2, miR-889-3p, MCTS1 and IL-6 regulates the malignant progression of LSCC. circHIPK2 expression may serve as a novel diagnostic and prognostic biomarker for LSCC.

摘要

喉鳞状细胞癌(LSCC)是一种常见的头颈部恶性肿瘤,预后较差。环状RNA(circRNAs)在LSCC中的作用仍 largely未知。在本研究中,采用定量实时聚合酶链反应(qRT-PCR)、桑格测序和荧光原位杂交技术检测环状HIPK2(circHIPK2)在LSCC组织及TU686和TU212细胞中的表达、定位及临床意义。通过增殖分析、EdU染色、集落形成实验、伤口愈合实验和Transwell实验探索circHIPK2在LSCC中的功能。利用荧光素酶实验、蛋白质免疫印迹法和qRT-PCR研究circHIPK2、微小RNA-889-3p(miR-889-3p)和MCTS1相互之间的调控机制。我们发现,LSCC组织和细胞中circHIPK2呈高表达,且与LSCC的恶性进展及不良预后密切相关。敲低circHIPK2可抑制LSCC细胞在体外的增殖和迁移。机制研究表明,circHIPK2与miR-889-3p竞争性结合,提高MCTS1水平,促进白细胞介素-6(IL-6)分泌,最终加速LSCC的恶性进展。总之,由circHIPK2、miR-889-3p、MCTS1和IL-6组成的轴调控LSCC的恶性进展。circHIPK2表达可能作为LSCC一种新的诊断和预后生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb77/12018564/02a8e8f03273/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb77/12018564/431239f09024/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb77/12018564/a960ea22e318/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb77/12018564/8df3c6ba1381/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb77/12018564/9b358a2d905f/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb77/12018564/574e38108816/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb77/12018564/2cefb7eeea25/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb77/12018564/02a8e8f03273/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb77/12018564/431239f09024/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb77/12018564/a960ea22e318/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb77/12018564/8df3c6ba1381/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb77/12018564/9b358a2d905f/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb77/12018564/574e38108816/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb77/12018564/2cefb7eeea25/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb77/12018564/02a8e8f03273/gr7.jpg

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本文引用的文献

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Mol Oncol. 2025 Jun;19(6):1876-1893. doi: 10.1002/1878-0261.13821. Epub 2025 Feb 18.
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Human papillomavirus-encoded circular RNA circE7 promotes immune evasion in head and neck squamous cell carcinoma.人乳头瘤病毒编码的环状 RNA circE7 促进头颈部鳞状细胞癌的免疫逃逸。
Nat Commun. 2024 Oct 4;15(1):8609. doi: 10.1038/s41467-024-52981-4.
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Plasma circRNA HIPK2 as a putative biomarker for the diagnosis and prediction of therapeutic effects in major depressive disorder.
血浆环状 RNA HIPK2 作为一种用于重度抑郁症诊断和治疗效果预测的潜在生物标志物。
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Proliferation-associated 2G4 P48 is stabilized by malignant T-cell amplified sequence 1 and promotes the proliferation of head and neck squamous cell carcinoma.增殖相关的2G4 P48由恶性T细胞扩增序列1稳定,并促进头颈部鳞状细胞癌的增殖。
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MCTS1 enhances the proliferation of laryngeal squamous cell carcinoma via promoting OTUD6B-1 mediated LIN28B deubiquitination.MCTS1 通过促进 OTUD6B-1 介导的 LIN28B 去泛素化来增强喉鳞状细胞癌的增殖。
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The Prognostic Utilities of Various Risk Factors for Laryngeal Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis.各种喉鳞状细胞癌风险因素的预后实用工具:系统评价和荟萃分析。
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