NNMT Promotes the Progression of Intrahepatic Cholangiocarcinoma by Regulating Aerobic Glycolysis Via the EGFR-STAT3 Axis

Overview

Journal Oncogenesis

Date 2022 Jul 19

PMID 35851575

Authors

Shounan Lu

Shanjia Ke

Chaoqun Wang

Yanan Xu

Zihao Li

Keda Song

Miaoyu Bai

Menghua Zhou

Hongjun Yu

Bing Yin

Xinglong Li

Zhigang Feng

Yongliang Hua

Shangha Pan

Hongchi Jiang

Linqiang Li

Yaohua Wu

Yong Ma

Affiliations

Soon will be listed here.

Abstract

Nicotinamide N-methyltransferase (NNMT), a member of the N-methyltransferase family, plays an important role in tumorigenesis. However, its expression and biological functions in intrahepatic cholangiocarcinoma (iCCA) remain to be established. In our study, we identified NNMT as an oncogene in iCCA and provided mechanistic insights into the roles of NNMT in iCCA progression. High NNMT expression in iCCA tissues was identified using western blotting and immunohistochemistry (IHC). We identified a significantly higher NNMT expression level in human iCCA tissues than that in adjacent normal tissues. Increased NNMT expression promoted iCCA cell proliferation and metastasis in vitro and in vivo. Mechanistically, NNMT inhibited the level of histone methylation in iCCA cells by consuming the methyl donor S-adenosyl methionine (SAM), thereby promoting the expression of epidermal growth factor receptor (EGFR). EGFR may activate the aerobic glycolysis pathway in iCCA cells by activating the STAT3 signaling pathway. In conclusion, we identified NNMT as an oncogene in iCCA and provided mechanistic insights into the roles of NNMT in iCCA progression.

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