丙戊酸和伽马射线在间变性甲状腺癌细胞中的放射增敏可增加hsa-miR-26a-5p的表达

IF 4.7 3区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Archives of Medical Research Pub Date : 2025-04-30 DOI:10.1016/j.arcmed.2025.103227

Marina Perona , Cecilia Grissi , Cinthia Rosemblit , Leonardo Salvarredi , Juan Pablo Nicola , Lisa Thomasz , María A. Dagrosa , Graciela Cremaschi , Hebe Durán , Guillermo Juvenal , Irene L. Ibañez

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引用次数: 0

摘要

背景：甲状腺增生性癌（ATC）是一种罕见的致死性恶性肿瘤，预后较差。多模式治疗，包括放疗，建议改善局部控制和生存。丙戊酸（VA）是一种临床可用的抗惊厥药和组蛋白去乙酰化酶抑制剂，具有良好的副作用记录。此外，VA对包括甲状腺癌在内的多种癌细胞具有放射致敏作用。MicroRNAs （miRs）在几种癌症中不受调节，可能调节辐射反应。因此，本研究的目的是分析VA联合伽马辐射对辐射耐药ATC细胞在mir表达水平上的影响。方法对satc细胞（8505c和KTC-2）进行va处理和2 Gy γ辐照。辐照后4 h，通过芯片分析评估8505c中miRs的表达谱。选择的miRs在两种类型的ATC细胞中通过RT-qPCR验证。结果我们观察到，在VA和γ射线联合照射后，8505c细胞与单独照射细胞相比，有109个miRs表达差异。hsa-miR-26a-5p在侵袭性甲状腺癌中通常下调，这些mir表现出放射致敏性。此外，在甲状腺肿瘤中经常失调的hsa-miR-27a-3p和hsa-miR-486-5p分别在辐照和VA治疗后下调。在处理后的8505c和KTC-2细胞中验证了这三种miRs的表达水平。结论VA和γ辐照对miR的调控揭示了一种新的miR表达谱，在ATC细胞的放射诱导反应和放射增敏中有进一步研究的潜力。

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Radiosensitization Following Valproic Acid and Gamma Rays in Anaplastic Thyroid Cancer Cells Increases the Expression of hsa-miR-26a-5p

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Radiosensitization Following Valproic Acid and Gamma Rays in Anaplastic Thyroid Cancer Cells Increases the Expression of hsa-miR-26a-5p

Background

Anaplastic thyroid cancer (ATC) is a rare lethal human malignancy with a poor prognosis. Multimodality treatment, including radiotherapy, is recommended to improve local control and survival. Valproic acid (VA) is a clinically available anticonvulsant and histone deacetylase inhibitor with a well-documented side effect profile. Furthermore, VA radiosensitizes various cancer cells, including thyroid cancer. MicroRNAs (miRs) are deregulated in several cancers and may modulate radiation response. Therefore, the aim of this study was to analyze the effect of VA combined with gamma radiation in radioresistant ATC cells at the expression level of miRs.

Methods

ATC cells (8505c and KTC-2) were VA-treated and gamma-irradiated (2 Gy). The expression profile of miRs in 8505c was evaluated by microarray analysis 4 h after irradiation. Selected miRs were validated by RT-qPCR in both types of ATC cells.

Results

We observed that after combined VA and gamma irradiation treatment, 8505c cells showed 109 differentially expressed miRs as compared to irradiated cells alone. These miRs exhibited a radiosensitization profile highlighted by upregulation of hsa-miR-26a-5p, which is usually downregulated in aggressive thyroid cancers. Moreover, hsa-miR-27a-3p and hsa-miR-486–5p, which are often deregulated in thyroid neoplasms, were downregulated after irradiation and VA treatment, respectively. The expression level of these three miRs was validated in 8505c and KTC-2 cells after treatments.

Conclusion

The regulated miRs by VA and gamma irradiation reveal a novel miR expression profile with potential to be further studied in the radio-induced response and radiosensitization of ATC cells.

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来源期刊

Archives of Medical Research 医学-医学：研究与实验

CiteScore

12.50

自引率

0.00%

发文量

审稿时长

28 days

期刊介绍： Archives of Medical Research serves as a platform for publishing original peer-reviewed medical research, aiming to bridge gaps created by medical specialization. The journal covers three main categories - biomedical, clinical, and epidemiological contributions, along with review articles and preliminary communications. With an international scope, it presents the study of diseases from diverse perspectives, offering the medical community original investigations ranging from molecular biology to clinical epidemiology in a single publication.