Overexpression of HOXA10 promotes the growth and metastasis of nasopharyngeal carcinoma

Deregulation of HOX transcription factor family has frequently been observed in multiple human cancers; however, their role in nasopharyngeal carcinoma remains largely unclear. In the present study, we found that HOX gene family is consistently upregulated in nasopharyngeal carcinoma and identified...

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Veröffentlicht in:Experimental biology and medicine (Maywood, N.J.) N.J.), 2021-12, Vol.246 (23), p.2454-2462
Hauptverfasser: Gong, Dan, Zhu, Hui, Zeng, Lei, Hu, Ronghuan, Hu, Jiali, Ding, Jianwu
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container_issue 23
container_start_page 2454
container_title Experimental biology and medicine (Maywood, N.J.)
container_volume 246
creator Gong, Dan
Zhu, Hui
Zeng, Lei
Hu, Ronghuan
Hu, Jiali
Ding, Jianwu
description Deregulation of HOX transcription factor family has frequently been observed in multiple human cancers; however, their role in nasopharyngeal carcinoma remains largely unclear. In the present study, we found that HOX gene family is consistently upregulated in nasopharyngeal carcinoma and identified HOXA10 as one of the mostly upregulated HOX genes. Importantly, we show that HOXA10 overexpression is associated with transcriptional activation of multiple oncogenes essential for nasopharyngeal carcinoma carcinogenesis, including S-phase kinase-associated protein 2 (SKP2), calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2), and matrix metalloproteinase 1 (MMP1). Mechanistically, the overexpression of SKP2 induces the degradation of cell cycle inhibitor p27, leading to rapid cell cycle progression and cell proliferation. The overexpression of CAMKK2 is associated with enhanced mTOR signaling activity to meet the increased demand for proteins synthesis in rapid growing nasopharyngeal carcinoma cells. Moreover, MMP1 overexpression facilitates nasopharyngeal carcinoma cell migration and invasion and contributes to cancer metastasis and progression. We thus concluded that HOXA10 overexpression promotes the growth and metastasis of nasopharyngeal carcinoma by transcriptionally activating various oncogenic pathways.
doi_str_mv 10.1177/15353702211030854
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In the present study, we found that HOX gene family is consistently upregulated in nasopharyngeal carcinoma and identified HOXA10 as one of the mostly upregulated HOX genes. Importantly, we show that HOXA10 overexpression is associated with transcriptional activation of multiple oncogenes essential for nasopharyngeal carcinoma carcinogenesis, including S-phase kinase-associated protein 2 (SKP2), calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2), and matrix metalloproteinase 1 (MMP1). Mechanistically, the overexpression of SKP2 induces the degradation of cell cycle inhibitor p27, leading to rapid cell cycle progression and cell proliferation. The overexpression of CAMKK2 is associated with enhanced mTOR signaling activity to meet the increased demand for proteins synthesis in rapid growing nasopharyngeal carcinoma cells. Moreover, MMP1 overexpression facilitates nasopharyngeal carcinoma cell migration and invasion and contributes to cancer metastasis and progression. 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subjects Calcium-Calmodulin-Dependent Protein Kinase Kinase - genetics
Calcium-Calmodulin-Dependent Protein Kinase Kinase - metabolism
Carcinogenesis - genetics
Cell Line, Tumor
Cell Movement - genetics
Cell Proliferation - genetics
Cyclin-Dependent Kinase Inhibitor p27 - metabolism
Homeobox A10 Proteins - genetics
Homeobox A10 Proteins - metabolism
Humans
Matrix Metalloproteinase 1 - genetics
Matrix Metalloproteinase 1 - metabolism
Nasopharyngeal Carcinoma - genetics
Nasopharyngeal Carcinoma - pathology
Nasopharyngeal Neoplasms - genetics
Nasopharyngeal Neoplasms - pathology
Original Research
RNA Interference
RNA, Small Interfering - genetics
S-Phase Kinase-Associated Proteins - genetics
S-Phase Kinase-Associated Proteins - metabolism
TOR Serine-Threonine Kinases - metabolism
Transcriptional Activation - genetics
Up-Regulation - genetics
title Overexpression of HOXA10 promotes the growth and metastasis of nasopharyngeal carcinoma
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