CircRNA PVT1 promotes migration, invasion and glucose metabolism of thyroid cancer cells through modulating the miR-195-5p-PDK4 axis.

IF 2.2 4区生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Cytotechnology Pub Date : 2026-10-01 Epub Date: 2026-08-12 DOI:10.1007/s10616-026-00960-6

Huanli Hu, Yanan Lu, Yingchuan Sun, Xue Liu

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引用次数: 0

Abstract

This study aimed to investigate the biological functions and underlying molecular mechanisms of circular RNA plasmacytoma variant translocation 1 (circPVT1) in the progression of thyroid cancer.The expression levels of circPVT1 in thyroid tumor tissues and cell lines were compared to normal controls, and its association with clinicopathological features was analyzed. Functional assays were performed to assess the effects of circPVT1 silencing on thyroid cancer cell migration, invasion, and glucose metabolism. The interaction between circPVT1 and miR-195-5p was validated using bioinformatics prediction, RNA pull-down, dual-luciferase reporter assays, and RNA fluorescence in situ hybridization (FISH). The target relationship between miR-195-5p and pyruvate dehydrogenase kinase 4 (PDK4) was examined via luciferase reporter and Western blot assays. Rescue and epistasis experiments were conducted by restoring miR-195-5p expression or knocking down PDK4 in circPVT1-overexpressing cells. The role of the circPVT1/miR-195-5p/PDK4 axis was further validated in vivo using subcutaneous xenograft and experimental lung metastasis models.circPVT1 was significantly upregulated in thyroid tumors and cell lines, and its high expression correlated with advanced TNM stage and lymph node metastasis. Silencing circPVT1 suppressed migration, invasion, and glycolytic metabolism of thyroid cancer cells. Mechanistically, circPVT1 acted as a sponge for miR-195-5p, downregulating its expression, and miR-195-5p directly targeted and inhibited PDK4. Restoration of miR-195-5p or knockdown of PDK4 reversed the oncogenic phenotypes induced by circPVT1 overexpression. In vivo, circPVT1 promoted tumor growth and lung metastasis, which were attenuated by co-expression of miR-195-5p. Molecular analysis of lung metastases confirmed the dysregulation of the circPVT1/miR-195-5p/PDK4 axis within metastatic lesions.CircPVT1 promotes migration, invasion, glycolytic metabolism, and metastasis in thyroid cancer by sponging miR-195-5p and upregulating PDK4. These findings highlight the circPVT1/miR-195-5p/PDK4 axis as a potential therapeutic target for thyroid cancer intervention.

Supplementary information: The online version contains supplementary material available at 10.1007/s10616-026-00960-6.

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CircRNA PVT1通过调节miR-195-5p-PDK4轴促进甲状腺癌细胞的迁移、侵袭和糖代谢。

本研究旨在探讨环状RNA浆细胞瘤变异易位1 （circPVT1）在甲状腺癌进展中的生物学功能和潜在的分子机制。将circPVT1在甲状腺肿瘤组织和细胞系中的表达水平与正常对照进行比较，并分析其与临床病理特征的关系。通过功能分析来评估circPVT1沉默对甲状腺癌细胞迁移、侵袭和葡萄糖代谢的影响。circPVT1和miR-195-5p之间的相互作用通过生物信息学预测、RNA下拉、双荧光素酶报告基因测定和RNA荧光原位杂交（FISH）验证。通过荧光素酶报告基因和Western blot检测miR-195-5p与丙酮酸脱氢酶激酶4 （PDK4）的靶标关系。在circpvt1过表达的细胞中，通过恢复miR-195-5p表达或敲低PDK4进行挽救和显存实验。circPVT1/miR-195-5p/PDK4轴的作用通过皮下异种移植和实验性肺转移模型在体内得到进一步验证。circPVT1在甲状腺肿瘤和细胞系中显著上调，其高表达与TNM晚期和淋巴结转移相关。沉默circPVT1可抑制甲状腺癌细胞的迁移、侵袭和糖酵解代谢。在机制上，circPVT1作为miR-195-5p的海绵，下调其表达，miR-195-5p直接靶向并抑制PDK4。恢复miR-195-5p或敲低PDK4可逆转circPVT1过表达诱导的致癌表型。在体内，circPVT1促进肿瘤生长和肺转移，而miR-195-5p的共表达减弱了这一作用。肺转移的分子分析证实了转移灶中circPVT1/miR-195-5p/PDK4轴的失调。CircPVT1通过抑制miR-195-5p和上调PDK4促进甲状腺癌的迁移、侵袭、糖酵解代谢和转移。这些发现强调circPVT1/miR-195-5p/PDK4轴是甲状腺癌干预的潜在治疗靶点。补充信息：在线版本包含补充资料，可在10.1007/s10616-026-00960-6获得。

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来源期刊

Cytotechnology 生物-生物工程与应用微生物

CiteScore

4.10

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： The scope of the Journal includes: 1. The derivation, genetic modification and characterization of cell lines, genetic and phenotypic regulation, control of cellular metabolism, cell physiology and biochemistry related to cell function, performance and expression of cell products. 2. Cell culture techniques, substrates, environmental requirements and optimization, cloning, hybridization and molecular biology, including genomic and proteomic tools. 3. Cell culture systems, processes, reactors, scale-up, and industrial production. Descriptions of the design or construction of equipment, media or quality control procedures, that are ancillary to cellular research. 4. The application of animal/human cells in research in the field of stem cell research including maintenance of stemness, differentiation, genetics, and senescence, cancer research, research in immunology, as well as applications in tissue engineering and gene therapy. 5. The use of cell cultures as a substrate for bioassays, biomedical applications and in particular as a replacement for animal models.