Nicotinamide N-methyltransferase induces the proliferation and invasion of squamous cell carcinoma cells
Nicotinamide N-methyltransferase induces the proliferation and invasion of squamous cell carcinoma cells
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DOI：
10.3892/or.2019.7315
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发表时间：
2019-11-01
期刊：
影响因子：
4.2
通讯作者：
Yoon, Tae-Jin
中科院分区：
文献类型：
--
作者：
Hah, Young-Sool;Cho, Hee Young;Yoon, Tae-Jin
皮肤鳞状细胞癌（cSCC）是一种由表皮角质形成细胞引发的常见恶性肿瘤，它能够侵入真皮层及其周围。虽然大多数cSCC患者存在可治愈的局部肿瘤，但偶尔会发生复发、转移和死亡。本研究发现，烟酰胺n -甲基转移酶（nicotinamide N-methyltransferase， NNMT）在SCC12细胞系中表达上调，与SCC13细胞系相比具有较高的侵袭潜力。研究了NNMT基因敲除对SCC细胞增殖、迁移和侵袭的影响。shrna介导的NNMT表达水平下调抑制SCC12细胞的增殖和密度依赖性生长。此外，细胞运动实验结果显示，nnmt敲除细胞后，SCC细胞的迁移和侵袭能力明显降低。利用PCR阵列分析评估上皮-间质转化（epithelial-mesenchymal transition， EMT）相关基因的表达发现，NNMT高表达水平伴随着EMT相关基因的高表达，NNMT敲低可有效抑制SCC12细胞中基质金属蛋白酶9、骨桥蛋白、versican core蛋白和锌指蛋白SNAI2的表达。这些结果表明，NNMT的上调是通过emt相关基因的表达诱导SCC细胞侵袭的。
Cutaneous squamous cell carcinoma (cSCC) is a common malignancy initiated by keratinocytes of the epidermis, which are able to invade the dermis and its periphery. Although most patients with cSCC present with curable localized tumors, recurrence, metastasis and mortality occasionally occur. In the present study, nicotinamide N-methyltransferase (NNMT) was identified as an upregulated protein in the SCC12 cell line, which has high invasive potential compared with the SCC13 cell line. The effects of NNMT knockdown on proliferation, migration and invasion were investigated using SCC cells. shRNA-mediated downregulation of NNMT expression levels inhibited the proliferation and density-dependent growth of SCC12 cells. In addition, the results of a cell motility assay showed that the migration and invasion of SCC cells were markedly decreased in NNMT-knockdown cells. The assessment of epithelial-mesenchymal transition (EMT)-associated gene expression using PCR array analysis revealed that high NNMT expression levels were accompanied by high expression levels of EMT-associated genes, and that NNMT knockdown effectively suppressed the expression of matrix metalloproteinase 9, osteopontin, versican core protein and zinc finger protein SNAI2 in SCC12 cells. These results revealed that the upregulation of NNMT induced cellular invasion via EMT-related gene expression in SCC cells.