HOXA1 promotes epithelial-mesenchymal transition and malignant characteristics of laryngeal squamous cell carcinoma

IF 1.5 4区医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis Pub Date : 2024-07-01 DOI:10.1016/j.mrfmmm.2024.111882

Jun Wu, Xiaofeng Gu

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引用次数: 0

Abstract

Despite considerable advancements in the diagnosis and treatment of LSCC, there has been no significant improvement in survival rate. Consequently, identifying molecular targets for this cancer is of paramount importance. HOXA1, a constituent of the homeobox transcription factor cluster, plays a role in the development of various types of cancer. Nevertheless, the specific function and mechanism of HOXA1 in LSCC remains unclear. This study aimed to clarify the impact of HOXA1 on the advancement of LSCC and uncover its underlying mechanism. Our findings indicate that HOXA1 exhibits a significantly elevated expression level in LSCC. Suppression of HOXA1 inhibited the proliferation of LSCC cells. Furthermore, the ablation of HOXA1 triggered the apoptosis of LSCC cells and inhibited EMT. Functionally, HOXA1 has a role in initiating the activation of the PI3K/AKT/mTOR pathway in LSCC cells. In summary, HOXA1 significantly contributes to the EMT of LSCC cells via the PI3K/AKT/mTOR signaling pathway, thereby facilitating the proliferation and motility of LSCC cells. Consequently, HOXA1 presents itself as a viable therapeutic target for LSCC interventions.

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HOXA1 促进上皮-间质转化和喉鳞癌的恶性特征。

尽管 LSCC 的诊断和治疗取得了长足的进步，但存活率却没有明显提高。因此，确定这种癌症的分子靶点至关重要。HOXA1是homeobox转录因子集群的一个组成部分，在各种癌症的发展中起着重要作用。然而，HOXA1在LSCC中的具体功能和机制仍不清楚。本研究旨在阐明HOXA1对LSCC进展的影响，并揭示其潜在机制。我们的研究结果表明，HOXA1在LSCC中的表达水平明显升高。抑制HOXA1可抑制LSCC细胞的增殖。此外，消融HOXA1可诱导LSCC细胞凋亡并抑制EMT。从功能上看，HOXA1 在激活 LSCC 细胞的 PI3K/AKT/mTOR 通路中发挥作用。总之，HOXA1通过PI3K/AKT/mTOR信号通路显著促进了LSCC细胞的EMT，从而促进了LSCC细胞的增殖和运动。因此，HOXA1可作为干预LSCC的可行治疗靶点。

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

Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis 生物-毒理学

CiteScore

4.90

自引率

0.00%

发文量

审稿时长

51 days

期刊介绍： Mutation Research (MR) provides a platform for publishing all aspects of DNA mutations and epimutations, from basic evolutionary aspects to translational applications in genetic and epigenetic diagnostics and therapy. Mutations are defined as all possible alterations in DNA sequence and sequence organization, from point mutations to genome structural variation, chromosomal aberrations and aneuploidy. Epimutations are defined as alterations in the epigenome, i.e., changes in DNA methylation, histone modification and small regulatory RNAs. MR publishes articles in the following areas: Of special interest are basic mechanisms through which DNA damage and mutations impact development and differentiation, stem cell biology and cell fate in general, including various forms of cell death and cellular senescence. The study of genome instability in human molecular epidemiology and in relation to complex phenotypes, such as human disease, is considered a growing area of importance. Mechanisms of (epi)mutation induction, for example, during DNA repair, replication or recombination; novel methods of (epi)mutation detection, with a focus on ultra-high-throughput sequencing. Landscape of somatic mutations and epimutations in cancer and aging. Role of de novo mutations in human disease and aging; mutations in population genomics. Interactions between mutations and epimutations. The role of epimutations in chromatin structure and function. Mitochondrial DNA mutations and their consequences in terms of human disease and aging. Novel ways to generate mutations and epimutations in cell lines and animal models.