HTR3A Promotes Non-small Cell Lung Cancer Through the FOXH1/Wnt3A Signaling Pathway.

IF 2.1 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical Genetics Pub Date : 2024-07-24 DOI:10.1007/s10528-024-10872-9

Zeqin Wu, Jiufei Li, Minglian Zhong, Zhiyuan Xu, Mulan Yang, Chenyang Xu

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引用次数: 0

Abstract

5-Hydroxytryptamine receptors (5-HTRs) are strongly correlated with tumor progression in various types of cancer. Despite this, the underlying mechanisms responsible for the role of 5-HTRs in non-small cell lung cancer (NSCLC) remains unclear. This study aimed to investigate the relationship between 5-hydroxytryptamine receptor 3A (HTR3A) and NSCLC development. Our findings indicated a higher distribution of HTR3A expression in NSCLC tissues when compared with normal tissues, where patients with high HTR3A levels demonstrated shorter overall survival times. In vitro analyses revealed that overexpression of HTR3A facilitated the proliferation and migration of NSCLC cell lines (A549 and NCI-H3255). Similarly, a notable acceleration of tumor growth and enhanced pulmonary tumorigenic potential were observed in HTR3A-overexpressing tumor-bearing mice. Mechanistically, upregulation of Forkhead Box H1 (FOXH1) by HTR3A led to the activation of Wnt3A/β-catenin signaling pathways, thereby promoting the development of NSCLC. Our report thus highlights the significance of the HTR3A/FOXH1 axis during tumor progression in NSCLC, proposing HTR3A as a possible diagnostic indicator and candidate target for clinical therapy.

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HTR3A 通过 FOXH1/Wnt3A 信号通路促进非小细胞肺癌的发生

5-羟色胺受体（5-HTR）与各种癌症的肿瘤进展密切相关。尽管如此，5-HTRs 在非小细胞肺癌（NSCLC）中发挥作用的潜在机制仍不清楚。本研究旨在探讨5-羟色胺受体3A（HTR3A）与非小细胞肺癌发展之间的关系。我们的研究结果表明，与正常组织相比，HTR3A在NSCLC组织中的表达分布较高，HTR3A水平高的患者总生存时间较短。体外分析表明，HTR3A 的过表达促进了 NSCLC 细胞系（A549 和 NCI-H3255）的增殖和迁移。同样，在过表达 HTR3A 的肿瘤小鼠中也观察到肿瘤生长明显加速，肺部致瘤潜力增强。从机理上讲，HTR3A上调叉头盒H1（FOXH1）导致Wnt3A/β-catenin信号通路的激活，从而促进了NSCLC的发展。因此，我们的报告强调了HTR3A/FOXH1轴在NSCLC肿瘤进展过程中的重要性，并提出HTR3A可能是诊断指标和临床治疗的候选靶点。

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

Biochemical Genetics 生物-生化与分子生物学

CiteScore

3.90

自引率

0.00%

发文量

133

审稿时长

4.8 months

期刊介绍： Biochemical Genetics welcomes original manuscripts that address and test clear scientific hypotheses, are directed to a broad scientific audience, and clearly contribute to the advancement of the field through the use of sound sampling or experimental design, reliable analytical methodologies and robust statistical analyses. Although studies focusing on particular regions and target organisms are welcome, it is not the journal’s goal to publish essentially descriptive studies that provide results with narrow applicability, or are based on very small samples or pseudoreplication. Rather, Biochemical Genetics welcomes review articles that go beyond summarizing previous publications and create added value through the systematic analysis and critique of the current state of knowledge or by conducting meta-analyses. Methodological articles are also within the scope of Biological Genetics, particularly when new laboratory techniques or computational approaches are fully described and thoroughly compared with the existing benchmark methods. Biochemical Genetics welcomes articles on the following topics: Genomics; Proteomics; Population genetics; Phylogenetics; Metagenomics; Microbial genetics; Genetics and evolution of wild and cultivated plants; Animal genetics and evolution; Human genetics and evolution; Genetic disorders; Genetic markers of diseases; Gene technology and therapy; Experimental and analytical methods; Statistical and computational methods.