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热休克蛋白 90α 成员 1 通过调控上皮-间质转化促进下咽鳞癌的淋巴转移。

HSP90AA1 promotes lymphatic metastasis of hypopharyngeal squamous cell carcinoma by regulating epithelial-mesenchymal transition.

机构信息

Department of Otolaryngology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

出版信息

Oncol Res. 2023 Jul 21;31(5):787-803. doi: 10.32604/or.2023.030081. eCollection 2023.

Abstract

BACKGROUND

Lymphatic metastasis (LM) emerges as an independent prognostic marker for hypopharyngeal squamous cell carcinoma (HSPSCC), chiefly contributing to treatment inefficacy. This study aimed to scrutinize the prognostic relevance of HSP90AA1 and its potential regulatory mechanism of concerning LM in HPSCC.

METHODS

In a preceding investigation, HSP90AA1, a differential gene, was discovered through transcriptome sequencing of HPSCC tissues, considering both the presence and absence of LM. Validation of HSP90AA1 expression was accomplished via qRT-PCR, western-blotting(WB), and immunohistochemistry(IHC), while its prognostic significance was assessed employing Kaplan-Meier survival analysis(KMSA), log-rank test(LR), and Cox's regression analysis(CRA). Bioinformatics techniques facilitated the prediction and analysis of its plausible mechanisms in LM, further substantiated by and experiments utilizing FaDu cell lines.

RESULTS

HSP90AA1 is substantially up-regulated in HPSCC with LM and is identified as an independent prognostic risk determinant. The down-regulation of HSP90AA1 can achieve inhibition of tumor cell proliferation, migration and invasion. Both experiments and Bioinformatics exploration hint at promoting LM by Epithelial-mesenchymal transition (EMT), regulated by HSP90AA1.

CONCLUSIONS

HSP90AA1, by controlling EMT, can foster LM in HPSCC.This finding sets the foundation for delving into new therapeutic targets for HPSCC.

摘要

背景

淋巴转移(LM)是下咽鳞癌(HSPSCC)的一个独立预后标志物,主要导致治疗无效。本研究旨在探讨 HSP90AA1 在 HSPSCC 中的预后相关性及其潜在的 LM 调控机制。

方法

在之前的研究中,通过对有或无 LM 的 HSPSCC 组织进行转录组测序,发现 HSP90AA1 是一个差异基因。通过 qRT-PCR、western-blotting(WB)和免疫组织化学(IHC)验证 HSP90AA1 的表达,通过 Kaplan-Meier 生存分析(KMSA)、对数秩检验(LR)和 Cox 回归分析(CRA)评估其预后意义。生物信息学技术预测和分析其在 LM 中的可能机制,并通过 FaDu 细胞系进行 和 实验进一步证实。

结果

HSP90AA1 在有 LM 的 HSPSCC 中显著上调,被确定为独立的预后风险决定因素。下调 HSP90AA1 可以抑制肿瘤细胞的增殖、迁移和侵袭。和 实验以及生物信息学探索都暗示 HSP90AA1 通过上皮-间充质转化(EMT)促进 LM。

结论

HSP90AA1 通过控制 EMT 促进 HSPSCC 中的 LM。这一发现为研究 HSPSCC 的新治疗靶点奠定了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/feb9/10398399/56661ad87286/OncolRes-31-30081-f001.jpg

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