Siglec15激活PI3K/AKT通路并促进肝细胞癌恶性进展

doi:10.3870/j.issn.1672-8009.2026.05.005

医学分子生物学杂志 ›› 2026, Vol. 23 ›› Issue (5): 514-522.doi: 10.3870/j.issn.1672-8009.2026.05.005

Siglec15激活PI3K/AKT通路并促进肝细胞癌恶性进展

牛宇杰¹, 马湘宇¹, 林文¹, 关璐璐², 郭彩茹^1,3

洛阳市中心医院 ¹中心实验室, ²洛阳市肝癌个体化治疗重点实验室河南省洛阳市, 471000;
³河南省肿瘤免疫与再生医学国际联合实验室河南省洛阳市, 471000

收稿日期:2025-11-12 出版日期:2026-09-30 发布日期:2026-09-30
通讯作者: 郭彩茹（E-mail：cairuguo@126.com）
基金资助:
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）

Siglec15 Activates the PI3K/AKT Signaling Pathway and Promotes Malignant Progression of Hepatocellular Carcinoma

NIU Yujie¹, MA Xiangyu¹, LIN Wen¹, GUAN Lulu², GUO Cairu^1,3

¹Central Laboratory, ²Luoyang Key Laboratory of Individualized Treatment of Liver Cancer, Luoyang Central Hospital, Luoyang, Henan, 471000, China;
³Henan Province International Joint Laboratory of Tumor Immunology and Regenerative Medicine, Luoyang, Henan, 471000, China

Received:2025-11-12 Online:2026-09-30 Published:2026-09-30
Contact: GUO Cairu （E-mail：cairuguo@126.com）
Supported by:
Luoyang Public Welfare Industry Medical and Health Special Project（No. 2302040Y） and the Henan Province Medical Science and Technology Research Program Joint Construction Project（No.LHGJ20230818）

摘要/Abstract

摘要： 目的探讨唾液酸结合性免疫球蛋白样凝集素-15 （sialic acid-bound immunoglobulin-like lectin 15, Siglec15）在肝细胞癌（hepatocellular carcinoma,HCC）发生发展中的作用及其潜在机制。方法利用在线数据库分析Siglec15在HCC的表达,并在肝癌细胞系中验证;构建Siglec15过表达/敲低的肝癌细胞模型,评估Siglec15对肝癌细胞增殖和迁移能力的影响;建立裸鼠皮下肿瘤模型,观察Siglec15过表达对肿瘤生长的作用。通过转录组测序、KEGG富集及qRT-PCR、蛋白质印迹验证相关信号通路。检测PI3K/AKT信号通路关键分子（p-PI3K、p-AKT）及细胞周期、凋亡相关蛋白（P53、Caspase3、Bax、Bcl-2）的表达变化。结果与正常肝组织相比,Siglec15在HCC组织中及肝癌细胞系中均显著高表达（P<0.05）。敲低Siglec15可显著抑制肝癌细胞SMMC-7721的增殖和迁移能力（P<0.05）。裸鼠成瘤实验显示,Siglec15过表达可促进肿瘤生长。测序筛选出4 765个差异基因,其中PI3K-AKT通路关键因子（PI3K、AKT、Bcl-2、CCNA2、P53等）表达变化与表型高度契合。验证实验表明,Siglec15过表达能上调PI3K、AKT、Bcl-2、CCNA2的mRNA表达,下调P53、Caspase3、Bax的表达;同时显著升高p-PI3K、p-AKT蛋白磷酸化水平,并相应调节下游凋亡与周期相关蛋白质。敲低组呈现相反趋势。结论 Siglec15通过激活PI3K/AKT信号通路（主要依赖翻译后磷酸化修饰）,调控下游凋亡与周期相关蛋白质表达,从而促进肝癌细胞增殖与迁移,其可能是HCC的潜在治疗靶点。

关键词: 肝细胞癌, Siglec15, 增殖, PI3K/AKT通路

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 underlying 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 overexpression or knockdown were established to evaluate the regulatory effects of Siglec15 on the proliferation and migration of HCC cells. A subcutaneous tumor xenograft model in nude mice was constructed 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 signaling 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 upregulated both in the HCC tissues and cell lines （P<0.05）. Knockdown of Siglec15 markedly suppressed 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 proteins, 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.

Key words: hepatocellular carcinoma, sialic acid-bound immunoglobulin-like lectin 15, proliferation, PI3K/AKT signaling pathway

中图分类号:

R735.7

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.

NIU Yujie, MA Xiangyu, LIN Wen, GUAN Lulu, GUO Cairu. Siglec15 Activates the PI3K/AKT Signaling Pathway and Promotes Malignant Progression of Hepatocellular Carcinoma[J]. Journal of Medical Molecular Biology, 2026, 23(5): 514-522.

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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

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