Objective Histamine N-methyltransferase(HNMT)is involved primarily in histamine metabolism,but emerging evidence suggests its potential role in cancer progression.This study investigated the role of HNMT in nasopharyn...Objective Histamine N-methyltransferase(HNMT)is involved primarily in histamine metabolism,but emerging evidence suggests its potential role in cancer progression.This study investigated the role of HNMT in nasopharyngeal carcinoma(NPC)and its impact on interferon(IFN)signaling,thioredoxin-interacting protein(TXNIP),and p53 tumor suppressor pathways.Methods HNMT expression in NPC tissues and cell lines was analyzed via qPCR and Western blotting.Functional assays,including cell proliferation,migration,invasion,and apoptosis,were performed after HNMT knockdown or overexpression.Transcriptomic sequencing was used to identify differentially expressed genes(DEGs).In addition,we examined the relationship between HNMT and the IFN/TXNIP/p53 axis via rescue experiments in vitro and in vivo models via qPCR and Western blotting.Results HNMT knockdown reduced cell proliferation,migration,and invasion,and promoted apoptosis in NPC tissues and cell lines.TXNIP was the most significantly upregulated gene following HNMT knockdown.Inhibition of the IFN pathway reversed these effects,confirming the role of HNMT in downregulating the IFN/TXNIP/p53 pathway.An in vivo study revealed that HNMT overexpression correlated with reduced expression of TXNIP and p53 in NCG mice.Conclusion In NPC,HNMT promotes tumor growth and progression by inhibiting the IFN/TXNIP/p53 axis.These findings suggest that targeting the HNMT axis or restoring its function could provide new therapeutic strategies for NPC.展开更多
基金supported by grants from Science Research Foundation of Yunnan Education Bureau(No.2023Y0631)Yunnan Provincial Science and Technology Project(No.202303AP140005).
文摘Objective Histamine N-methyltransferase(HNMT)is involved primarily in histamine metabolism,but emerging evidence suggests its potential role in cancer progression.This study investigated the role of HNMT in nasopharyngeal carcinoma(NPC)and its impact on interferon(IFN)signaling,thioredoxin-interacting protein(TXNIP),and p53 tumor suppressor pathways.Methods HNMT expression in NPC tissues and cell lines was analyzed via qPCR and Western blotting.Functional assays,including cell proliferation,migration,invasion,and apoptosis,were performed after HNMT knockdown or overexpression.Transcriptomic sequencing was used to identify differentially expressed genes(DEGs).In addition,we examined the relationship between HNMT and the IFN/TXNIP/p53 axis via rescue experiments in vitro and in vivo models via qPCR and Western blotting.Results HNMT knockdown reduced cell proliferation,migration,and invasion,and promoted apoptosis in NPC tissues and cell lines.TXNIP was the most significantly upregulated gene following HNMT knockdown.Inhibition of the IFN pathway reversed these effects,confirming the role of HNMT in downregulating the IFN/TXNIP/p53 pathway.An in vivo study revealed that HNMT overexpression correlated with reduced expression of TXNIP and p53 in NCG mice.Conclusion In NPC,HNMT promotes tumor growth and progression by inhibiting the IFN/TXNIP/p53 axis.These findings suggest that targeting the HNMT axis or restoring its function could provide new therapeutic strategies for NPC.
