Transcriptome and metabolome sequencing identifies glutamate and LPAR1 as potential factors of anlotinib resistance in thyroid cancer.

IF 1.8 4区 医学 Q3 ONCOLOGY
Anti-Cancer Drugs Pub Date : 2024-09-01 Epub Date: 2024-05-31 DOI:10.1097/CAD.0000000000001626
Bin Liu, Ying Peng, Yanjun Su, Chang Diao, Jun Qian, Xiangxiang Zhan, Ruochuan Cheng
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引用次数: 0

Abstract

Objective: To explore the mechanism of anlotinib resistance in thyroid carcinoma.

Methods: We constructed an anlotinib-resistant thyroid carcinoma cell line and observed the effect of drug resistance on the functional activity of these cell lines. Transcriptome sequencing and metabolomic sequencing combined with biosynthesis analysis were used to explore and screen possible drug resistance regulatory pathways.

Results: Through transcriptomic sequencing analysis of drug-resistant cell lines, it was found that the differentially expressed genes of drug-resistant strains were enriched mainly in the interleukin 17, transforming growth factor-β, calcium, peroxisome proliferator activated receptor, and other key signaling pathways. A total of 354 differentially expressed metabolic ions were screened using liquid chromatography-mass spectrometry/mass spectrometry to determine the number of metabolic ions in the drug-resistant strains. The results of the Venn diagram correlation analysis showed that glutamate is closely related to multiple pathways and may be an important regulatory factor of anlotinib resistance in thyroid carcinoma. In addition, eight common differentially expressed genes were screened by comparing the gene expression profiling interactive analysis database and sequencing results. Further quantitative real time polymerase chain reaction verification, combined with reports in the literature, showed that LPAR1 may be an important potential target.

Conclusion: This is the first study in which the drug resistance of thyroid cancer to anlotinib was preliminarily discussed. We confirmed that anlotinib resistance in thyroid cancer promotes the progression of malignant biological behavior. We conclude that glutamate may be a potential factor for anlotinib resistance in thyroid cancer and that LPAR1 is also a potentially important target.

转录组和代谢组测序发现谷氨酸和LPAR1是甲状腺癌患者对安罗替尼耐药的潜在因素。
目的:探讨甲状腺癌的安罗替尼耐药机制:探索甲状腺癌对安罗替尼耐药的机制:方法:构建安罗替尼耐药甲状腺癌细胞系,观察耐药性对细胞系功能活性的影响。通过转录组测序和代谢组测序结合生物合成分析,探索和筛选可能的耐药性调控途径:通过对耐药细胞株的转录组测序分析,发现耐药株的差异表达基因主要富集在白细胞介素 17、转化生长因子-β、钙、过氧化物酶体增殖物激活受体等关键信号通路。利用液相色谱-质谱法/质谱法共筛选出354个差异表达的代谢离子,以确定耐药菌株中代谢离子的数量。维恩图相关性分析结果表明,谷氨酸与多种通路密切相关,可能是甲状腺癌中安罗替尼耐药的重要调控因素。此外,通过对比基因表达谱交互分析数据库和测序结果,筛选出8个常见的差异表达基因。结合文献报道,进一步的定量实时聚合酶链反应验证表明,LPAR1可能是一个重要的潜在靶点:这是首次初步探讨甲状腺癌对安罗替尼耐药性的研究。我们证实,甲状腺癌对安罗替尼耐药会促进恶性生物学行为的进展。我们得出结论,谷氨酸可能是甲状腺癌对安洛替尼耐药的潜在因素,LPAR1也是一个潜在的重要靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Anti-Cancer Drugs
Anti-Cancer Drugs 医学-药学
CiteScore
3.80
自引率
0.00%
发文量
244
审稿时长
3 months
期刊介绍: Anti-Cancer Drugs reports both clinical and experimental results related to anti-cancer drugs, and welcomes contributions on anti-cancer drug design, drug delivery, pharmacology, hormonal and biological modalities and chemotherapy evaluation. An internationally refereed journal devoted to the fast publication of innovative investigations on therapeutic agents against cancer, Anti-Cancer Drugs aims to stimulate and report research on both toxic and non-toxic anti-cancer agents. Consequently, the scope on the journal will cover both conventional cytotoxic chemotherapy and hormonal or biological response modalities such as interleukins and immunotherapy. Submitted articles undergo a preliminary review by the editor. Some articles may be returned to authors without further consideration. Those being considered for publication will undergo further assessment and peer-review by the editors and those invited to do so from a reviewer pool.
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