医学分子生物学杂志2026，Vol.23Issue(5)：514-522,9.
Siglec15激活PI3K/AKT通路并促进肝细胞癌恶性进展
Siglec15 Activates the PI3K/AKT Signaling Pathway and Promotes Malignant Progression of Hepatocellular Carcinoma
摘要
Abstract
Objective To investigate the role of sialic acid-bound immunoglobulin-like lectin 15(Siglec15)in the occurrence and development of hepatocellular carcinoma(HCC)and its underly-ing mechanism.Methods Online databases were utilized to analyze the expression pattern of Siglec15 in HCC,followed by validation in HCC cell lines.HCC cell models with Siglec15 overex-pression or knockdown were established to evaluate the regulatory effects of Siglec15 on the prolifera-tion and migration of HCC cells.A subcutaneous tumor xenograft model in nude mice was con-structed to observe the impact of Siglec15 overexpression on tumor growth in vivo.Transcriptome sequencing combined with KEGG pathway enrichment analysis was performed,and the related sig-naling pathways were further verified by qRT-PCR and Western blotting.Moreover,the expression levels of key molecules in the PI3K/AKT signaling pathway(p-PI3K,p-AKT)as well as proteins associated with cell cycle regulation and apoptosis(P53,Caspase3,Bax,Bcl-2)were detected.Results Compared with that in the adjacent normal liver tissues,Siglec15 was significantly upregu-lated both in the HCC tissues and cell lines(P<0.05).Knockdown of Siglec15 markedly sup-pressed the proliferation and migration capacities of the HCC cell line SMMC-7721(P<0.05).The nude mouse xenograft experiment demonstrated that Siglec15 overexpression promoted tumor growth in vivo.Transcriptome sequencing identified 4 765 differentially expressed genes,among which the expression alterations of core moleculars involved in the PI3K-AKT pathway(PI3K,AKT,Bcl-2,CCNA2,P53,etc.)were highly consistent with the observed cellular phenotypes.Validation experiments confirmed that Siglec15 overexpression upregulated the mRNA expression of PI3K,AKT,Bcl-2 and CCNA2 while downregulating that of P53,Caspase3 and Bax.Meanwhile,Siglec15 overexpression significantly increased the phosphorylation levels of PI3K and AKT pro-teins,with concomitant modulation of the expression of downstream apoptosis and cell cycle-related proteins.Conversely,the Siglec15 knockdown group exhibited the opposite trends.Conclusion Siglec15 promotes the proliferation and migration of HCC cells by activating the PI3K/AKT signaling pathway,primarily via post-translational phosphorylation modification,which in turn regulates the expression of downstream apoptosis-and cell cycle-associated proteins.Therefore,Siglec15 may serve as a potential therapeutic target for HCC.关键词
肝细胞癌/Siglec15/增殖/PI3K/AKT通路Key words
hepatocellular carcinoma/sialic acid-bound immunoglobulin-like lectin 15/prolif-eration/PI3K/AKT signaling pathway分类
医药卫生引用本文复制引用
牛宇杰,马湘宇,林文,关璐璐,郭彩茹..Siglec15激活PI3K/AKT通路并促进肝细胞癌恶性进展[J].医学分子生物学杂志,2026,23(5):514-522,9.基金项目
洛阳市公益性行业医疗卫生专项(No.2302040Y),河南省医学科技攻关计划联合共建项目(No.LHGJ20230818) This work was supported by grants from the Luoyang Public Welfare Industry Medical and Health Special Project(No.2302040Y)and the Henan Prov-ince Medical Science and Technology Research Program Joint Construction Project(No.LHGJ20230818). （No.2302040Y）
