GSE171032
Nicotinamide N-methyltransferase is related to MELF pattern invasion in endometrioid carcinoma [RNA-seq]
In endometrioid carcinoma (EC), grade 1 (G1) EC is generally associated with a good prognosis. However, in a minority of G1, we often find a more aggressive histological pattern: MELF (microcystic, elongated, and fragmented) pattern. We previously revealed that EC with high expression of S100A4 and serum deprivation-response protein (SDPR) was related to MELF pattern invasion. However, the molecular feature of the invasive front area of MELF pattern has not been investigated. In the current study, we searched for genes preferentially expressed in the invasive front area of EC with MELF pattern by using laser microdissection and RNA sequencing, and revealed that Nicotinamide N-methyltransferase (NNMT) is related to invasiveness of MELF pattern. We confirmed that NNMT expression was high in the invasive front area of MELF pattern in immunohistochemical analysis. Moreover, using endometrioid carcinoma cell lines, we showed that NNMT promotes migration, invasion, colony formation, epithelial-mesenchymal transition (EMT), and chemoresistance. We speculated that depletion of NNMT promotes histone methylation and leads to tumor suppression because NNMT consumes S-adenosyl methionine (SAM), which is an essential methylation cofactor. We showed that NNMT-knockout cells the expression of H3K9me2 was enhanced. We speculate that methylation of H3K9 lead to repress the transcription of various oncogenic genes by performing RNA sequencing using NNMT-knockout cell lines. Our findings showed the possibility that NNMT inhibitors, which are expected to be used for the treatment of metabolic disorders, is effective for the treatment of an aggressive EC. This is the first report of the gene analysis focused on the morphological changes of MELF pattern invasion of EC. Overall design: To compare the levels of gene expression profiles between NNMT-knockout AN3CA cells and control cells, total RNA was extracted from KO1, KO2, and EV cells.