The Expression Characteristics,Clinical Relevance and Tumor Inhibition of KCNN3 in Gastric Adenocarcinoma
10.13865/j.cnki.cjbmb.2025.03.1535
- VernacularTitle:钾钙激活通道亚家族N成员3在胃腺癌中的表达特征、临床相关性及抑瘤功能
- Author:
Zi-Qing ZHAN
1
;
Jia-Bei JIN
;
Yu-Xuan LI
;
Jia-Xin SHI
;
Meng YE
;
Xiao-Feng JIN
Author Information
1. 宁波大学医学部生物化学与分子生物学系,浙江宁波 315211;宁波大学附属第一医院,浙江宁波 315010
- Publication Type:Journal Article
- Keywords:
stomach adenocarcinoma(STAD);
potassium calcium-activated channel subfamily N mem-ber 3(KCNN3/SK3/KCa2.3);
tumor necrosis factor receptor superfamily member 7(CD27/TNFRSF7);
drug sensitivity;
bioinformatics analysis
- From:
Chinese Journal of Biochemistry and Molecular Biology
2025;41(4):560-575,中插1-中插4
- CountryChina
- Language:Chinese
-
Abstract:
Potassium-calcium activates channel subfamily N member 3(KCNN3/SK3/KCa2.3)is in-volved in regulating cellular calcium signaling,muscle contraction and neurotransmitter release.Dysregu-lation of the KCNN3 channel is associated with the development of various tumors.We use bioinformatics analysis to identify whether KCNN3 regulates the occurrence and development of stomach adenocarcinoma(STAD)as a prognostic target.By analyzing the Human Protein Atlas(HPA)database and The Cancer Genome Atlas(TCGA)database,we found that the protein and mRNA levels of KCNN3 were dramatic-ally reduced in STAD,and TCGA database showed that KCNN3 significantly correlated with the prognosis and clinical features of STAD.In addition,we found that high expression of KCNN3 in STAD reduced the IC50 of several drugs in STAD cells,suggesting that high expression of KCNN3 correlated with the drug sensitivity of STAD.To investigate the underlying biological mechanism,we identified a potential KCNN3 interaction factor,tumor necrosis factor receptor superfamily member 7(CD27/TNFRSF7),which is expressed at low levels in STAD.RT-qPCR and Western blotting confirmed that KCNN3 and CD27 positively correlated with each other at protein and mRNA levels,and co-immunoprecipitation and immunofluorescence experiments confirmed that the two proteins interact and colocalize in the cytoplasm.Moreover,we confirmed the inhibitory effect of KCNN3 on the proliferation,migration and invasion of hu-man STAD cells in vitro and in vivo through subcutaneous tumorigenesis and cellular experiments.Fur-thermore,GO/KEGG enrichment analysis showed that KCNN3 was enriched in signaling pathways regula-ting the immune response and calcium or metal ion transport.Lastly,we verified through cell co-culture,RT-qPCR and CCK8 assays that high expression of KCNN3 can promote the increase of T cell activating factor and the killing effect of T cells on STAD cells.Therefore,our results suggest that KCNN3 is a po-tential inhibitory factor affecting the occurrence and progression of STAD.
