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Nicotinamide N?methyltransferase induces the proliferation and invasion of squamous cell carcinoma cells.

ABSTRACT: 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.

SUBMITTER: Hah YS

PROVIDER: S-EPMC6787961 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Nicotinamide N‑methyltransferase induces the proliferation and invasion of squamous cell carcinoma cells.

Hah Young-Sool YS Cho Hee Young HY Jo Sun Young SY Park Young Sook YS Heo Eun Phil EP Yoon Tae-Jin TJ

Oncology reports 20190916 5

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 ...[more]

PMID: 31545452

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Project description:Oral squamous cell carcinoma (OSCC) is an extremely aggressive disease associated with a poor prognosis. Previous studies have established that cancer stem cells (CSCs) actively participate in OSCC development, progression and resistance to conventional treatments. Furthermore, CSCs frequently exhibit a deregulated expression of normal stem cell signalling pathways, thereby acquiring their distinctive abilities, of which self-renewal is an example. In this study, we examined the effects of GLI3 knockdown in OSCC, as well as the differentially expressed genes in CSC-like cells (CSCLCs) expressing high (CD44high) or low (CD44low) levels of CD44. The prognostic value of GLI3 in OSCC was also evaluated. The OSCC cell lines were sorted based on CD44 expression; gene expression was evaluated using a PCR array. Following this, we examined the effects of GLI3 knockdown on CD44 and ESA expression, colony and sphere formation capability, stem-related gene expression, proliferation and invasion. The overexpression of genes related to the Notch, transforming growth factor (TGF)?, FGF, Hedgehog, Wnt and pluripotency maintenance pathways was observed in the CD44high cells. GLI3 knockdown was associated with a significant decrease in different CSCLC fractions, spheres and colonies in addition to the downregulation of the CD44, Octamer-binding transcription factor 4 (OCT4; also known as POU5F1) and BMI1 genes. This downregulation was accompanied by an increase in the expression of the Involucrin (IVL) and S100A9 genes. Cellular proliferation and invasion were inhibited following GLI3 knockdown. In OSCC samples, a high GLI3 expression was associated with tumour size but not with prognosis. On the whole, the findings of this study demonstrate for the first time, at least to the best of our knowledge, that GLI3 contributes to OSCC stemness and malignant behaviour. These findings suggest the potential for the development of novel therapies, either in isolation or in combination with other drugs, based on CSCs in OSCC.

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Nicotinamide N?methyltransferase induces the proliferation and invasion of squamous cell carcinoma cells.

Publications

Nicotinamide N‑methyltransferase induces the proliferation and invasion of squamous cell carcinoma cells.

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