J Cancer 2021; 12(14):4218-4228. doi:10.7150/jca.47506

Research Paper

The Overexpression of NMHC IIA Promoted Invasion and Metastasis of Nasopharyngeal Carcinoma Cells

Dan Xiong1#, Dayang Chen1#, Dawei Liu2#, Wei Wu1, Xiaowen Dou1, Xiang Ji1, Jian Li3,4✉, Xiuming Zhang1✉

1. Medical Laboratory of The Third Affiliated Hospital of ShenZhen university, Shenzhen, 518001, China.
2. Department of pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
3. Department of Otolaryngology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
4. Guangzhou Key Laboratory of Otorhinolaryngology, Guangzhou, China.
#These authors contributed equally to this paper.

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Citation:
Xiong D, Chen D, Liu D, Wu W, Dou X, Ji X, Li J, Zhang X. The Overexpression of NMHC IIA Promoted Invasion and Metastasis of Nasopharyngeal Carcinoma Cells. J Cancer 2021; 12(14):4218-4228. doi:10.7150/jca.47506. Available from https://www.jcancer.org/v12p4218.htm

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Abstract

Background: Nasopharyngeal carcinoma (NPC) is a kind of head and neck squamous cell carcinoma (HNSCC) with a strong tendency for metastasis and recurrence. Non-muscle myosin heavy chain IIA (NMHC IIA) plays important roles in recurrence and metastasis of cancers. However, the function and mechanism of NMHC IIA expression in NPC remain unclear.

Methods: A receiver operating characteristic (ROC) curve was constructed for 141 specimens of HNSCC tissues and 44 control samples from The Cancer Genome Atlas (TCGA) database. Co-expressed genes with MYH9 were identified using LinkedOmics. Transcription factors (TFs) and miRNA regulation network were constructed using Networkanalyst. The migration and invasion ability of nasopharyngeal carcinoma cells were evaluated by in vitro migration and matrigel invasion assays, respectively.

Results: The public microarray results showed that MYH9 expression levels were upregulated in HNSCC tissues compared with the matched adjacent normal tissues in this study (p<0.0001). The AUC of MYH9 reached up to 0.8303 at a cutoff value of 175.2, with a sensitivity and specificity of 70.21% and 86.36%, respectively. MYH9 expression was increased in lymph node metastasis HNSCC tumors compared with that in tumors without lymph node metastasis (p<0.05) and showed a strong positive association with expression of FLNA. High MYH9 and FLNA expression were related with poorer overall survival in HNSCC. MYH9 with positively associated genes regulated focal adhesion, cell-substrate junction assembly and cell morphogenesis were involved in differentiation using GO and KEGG analysis. MYH9 was correlated with a network of TFs including SP1, SRF, JUN and FOS in HNSCC. The suppression of endogenous NMHC IIA decreased cellular migration and invasion in HNE1 cells and reduced the expression of phosphorylation of EGFR, AKT and ERK. The over-expression of NMHC IIA increased cellular migration and invasion in COS-7 cells and increased the expression of phosphorylation of EGFR, AKT and ERK.

Conclusion: Expression of NMHC IIA mRNA was higher in HNSCC than in the adjacent normal tissues. NMHC IIA expression was increased in lymph node metastasis HNSCC tumors compared with tumors without lymph node metastasis. High MYH9 was association with poorer overall survival in HNSCC. NMHC IIA expression increased the invasion and metastasis abilities of the nasopharyngeal cancer cell line in vitro by augmenting the expression of phosphorylation of EGFR, AKT and ERK. These findings will be beneficial for providing an effectively therapeutic strategy for NPC.

Keywords: NMHC IIA, head and neck squamous cell carcinoma, nasopharyngeal cancer, invasion, metastasis