HOX 基因的上调促进头颈部鳞状细胞癌中的细胞迁移和增殖。

Upregulation of HOX genes promotes cell migration and proliferation in head and neck squamous cell carcinoma.

机构信息

Department of Medical Imaging, Hematology and Clinical Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.

Center of Cell-Based Therapy (CEPID/FAPESP), National Institute of Science and Technology in Stem Cell and Cell Therapy (INCTC/CNPq), Regional Blood Center of Ribeirão Preto, Ribeirão Preto, SP, Brazil.

出版信息

Tumour Biol. 2021;43(1):263-278. doi: 10.3233/TUB-211525.

DOI:10.3233/TUB-211525

PMID:34633333

Abstract

BACKGROUND

Expression dysregulation of HOX homeobox genes has been observed in several cancers, including head and neck squamous cell carcinoma (HNSC). Although characterization of HOX gene roles in HNSC development has been reported, there is still a need to better understand their real contribution to tumorigenesis.

OBJECTIVE

The present study aimed to evaluate the contribution of the protein-coding HOX genes (HOXA10, HOXC9, HOXC10, and HOXC13) in cellular processes related to carcinogenesis and progression of the HNSC.

METHODS

Expression of HOX genes was analyzed in HNSC RNA-Seq data from The Cancer Genome Atlas (TCGA) and by RT-qPCR in different tumor cell lines. siRNA-mediated knockdown of HOXA10, HOXC9, HOXC10 or HOXC13 was performed in HNSC cell lines, and predicted transcriptional targets HOX genes was analyzed by bioinformatic.

RESULTS

Thirty-one out of the 39 mammalian HOX genes were found upregulated in HNSC tissues and cell lines. The HOXC9, HOXC10 or HOXC13 knockdown attenuated cell migration, and lead to downregulation of epithelial-mesenchymal transition (EMT) markers, which were predicted as transcriptional targets of these three HOX genes. Diminished colony formation and cell cycle arrest after HOXC10 or HOXC13 knockdown were also observed, corroborating the fact that there was an enrichment for genes in proliferation/cell cycle pathways.

CONCLUSIONS

In summary, we revealed roles for HOXC9, HOXC10, and HOXC13 in cell migration and proliferation/cell cycle progression in HNSC cells and suggested that those HOX members contribute to HNSC development possibly by regulating tumor growth and metastasis.

摘要

背景

HOX 同源盒基因的表达失调已在多种癌症中观察到，包括头颈部鳞状细胞癌（HNSC）。尽管已经报道了 HOX 基因在 HNSC 发育中的作用特征，但仍需要更好地了解它们对肿瘤发生的真正贡献。

目的

本研究旨在评估蛋白编码 HOX 基因（HOXA10、HOXC9、HOXC10 和 HOXC13）在与 HNSC 癌变和进展相关的细胞过程中的贡献。

方法

分析了来自癌症基因组图谱（TCGA）的 HNSC RNA-Seq 数据和不同肿瘤细胞系中 HOX 基因的表达。在 HNSC 细胞系中，通过 siRNA 介导的 HOXA10、HOXC9、HOXC10 或 HOXC13 敲低，通过生物信息学分析预测 HOX 基因的转录靶标。

结果

在 HNSC 组织和细胞系中发现 39 种哺乳动物 HOX 基因中的 31 种上调。HOXC9、HOXC10 或 HOXC13 的敲低减弱了细胞迁移，并导致上皮-间充质转化（EMT）标志物下调，这些标志物被预测为这三个 HOX 基因的转录靶标。HOXC10 或 HOXC13 敲低后也观察到集落形成减少和细胞周期停滞，这证实了增殖/细胞周期途径中存在基因富集的事实。