|Table of Contents|

Knockdown of Siglec-15-mediated STAT1 pathway inhibits the proliferation and migration of SMMC-7721 in hepatocellular carcinoma cells

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2025 05
Page:
756-763
Research Field:
Publishing date:

Info

Title:
Knockdown of Siglec-15-mediated STAT1 pathway inhibits the proliferation and migration of SMMC-7721 in hepatocellular carcinoma cells
Author(s):
GUAN Lulu1GUO Cairu1YAN Jiawei2JIN Zili3WEN Xuejun4QI Min1
1.Luoyang Central Hospital,Henan Luoyang 471000,China;2.The First People's Hospital of Xinxiang City,Henan Xinxiang 453011,China;3.Xinxiang Medical College,Henan Xinxiang 453000,China;4.University of Virginia,Charlottesville Virginia 22903,USA.
Keywords:
Siglec-15STAT 1 pathwayhepatocellular carcinoma cellproliferation
PACS:
R735.7
DOI:
10.3969/j.issn.1672-4992.2025.05.006
Abstract:
Objective:To investigate the mechanism of knockdown of Siglec-15-mediated STAT1 pathway inhibiting the proliferation and migration of SMMC-7721 in hepatocellular carcinoma cells.Methods:Firstly,the expression of Siglec-15 in normal hepatocytes L02 and hepatocellular carcinoma cell lines SMMC-7721,BEL-7402 and HUH7 was detected by qRT-PCR and Western blot,and the transfection efficiency of siRNA knockdown of Siglec-15 was detected.The hepatocellular carcinoma cell line SMMC-7721 was divided into NC group and si-Siglec-15 group,and MTT,cell scratch and Transwell assays were used to detect the effect of knockdown of Siglec-15 on the proliferation and migration of hepatoma cells.The Cancer Genome Atlas Database (TCGA) was used to analyze the differentially expressed genes in the high and low expression groups of Siglec-15,and the Genome Database (KEGG) pathway was enriched to reveal the signaling pathways associated with Siglec-15.Furthermore,the interaction of Siglec-15 gene and related pathways was predicted by GeneMANIA database,which was related to STAT1,STAT2,STAT3,TYROBP,etc.,and the effect of Siglec-15 on STAT1 pathway was verified by Western blot,and finally Stattic (STAT inhibitor) was used to reversely verify its effect on Siglec-15 and its biological effect on hepatocellular carcinoma cells.Results:The expression level of Siglec-15 in the three hepatoma cell lines was significantly higher than that of L02 cells (P<0.05) and the transfection of Siglec-15 was successful.After knockdown of Siglec-15 in SMMC-7721 cells,the proliferation and migration ability of hepatoma cells in this group were significantly lower than those in the NC group (P<0.001),and the expression levels of STAT1,p-STAT1,STAT3 and p-STAT3 proteins were significantly decreased (P<0.001).The results of co-immunoprecipitation showed that Siglec-15 interacted with STAT1 protein,and the results of scratch assay showed that the migration of hepatocellular carcinoma SMMC-7721 cells was inhibited by inhibition of STAT1 pathway with Stattic (P<0.001).Conclusion:Knockdown of Siglec-15 mediates the STAT1 pathway to inhibit the proliferation and migration of HCC SMMC-7721 cells.

References:

[1] CHAKRABORTY E,SARKAR D.Emerging therapies for hepatocellular carcinoma (HCC)[J].Cancers (Basel),2022,14(11):2798-2804.
[2]YARCHOAN M,AGARWAL P,VILLANUEVA A,et al.Recent developments and therapeutic strategies against hepatocellular carcinoma[J].Cancer Res,2019,79(17):4326-4330.
[3]LONGO V,BRUNETTI O,GNONI A,et al.Emerging role of immune checkpoint inhibitors in hepatocellular carcinoma [J].Medicina (Kaunas,Lithuania),2019,55(10):698-704.
[4]XING R,GAO J,CUI Q,et al.Strategies to improve the antitumor effect of immunotherapy for hepatocellular carcinoma [J].Frontiers in Immunology,2021,12:783236.
[5] ANGATA TAKASHI.Siglec-15:an immune system Siglec conserved throughout vertebrate evolution [J].Glycobiology,2007,17(8):838-846.
[6]OWEN KL,BROCKWELL NK,PARKER BS.JAK-STAT signaling:A double-edged sword of immune regulation and cancer progression [J].Cancers (Basel),2019,11(12):2002-2008.
[7] HOU X,CHEN C,HE X,et al.Siglec-15 silencing inhibits cell proliferation and promotes cell apoptosis by inhibiting STAT1/STAT3 signaling in anaplastic thyroid carcinoma [J].Dis Markers,2022,2022:1606404.
[8] FORNER A,REIG M,BRUIX J.Hepatocellular carcinoma [J].Lancet,2018,391(10127):1301-1314.
[9] PETRICK JL,KELLY SP,ALTEKRUSE SF,et al.Future of hepatocellular carcinoma incidence in the United States forecast through 2030 [J].J Clin Oncol,2016,34(15):1787-1794.
[10]LIM JTC,KWANG LG,HO NCW,et al.Hepatocellular carcinoma organoid co-cultures mimic angiocrine crosstalk to generate inflammatory tumor microenvironment [J].Biomaterials,2022,284:121527.
[11] DONG S,GUO X,HAN F,et al.Emerging role of natural products in cancer immunotherapy [J].Acta Pharm Sin B,2022,12(3):1163-1185.
[12] RIMASSA L,FINN RS,SANGRO B.Combination immunotherapy for hepatocellular carcinoma [J].J Hepatol,2023,79(2):506-515.
[13] SHEN KY,ZHU Y,XIE SZ,et al.Immunosuppressive tumor microenvironment and immunotherapy of hepatocellular carcinoma:current status and prospectives [J].J Hematol Oncol,2024,17(1):25-30.
[14] OURA K,MORISHITA A,TANI J,et al.Tumor immune microenvironment and immunosuppressive therapy in hepatocellular carcinoma:a review [J].Int J Mol Sci,2021,22(11):5801-5807.
[15] SUN J,LU Q,SANMAMED MF,et al.Correction:Siglec-15 as an emerging target for next-generation cancer immunotherapy [J].Clin Cancer Res,2021,27(13):3804-3810.
[16] AHMAD MS,BRAOUDAKI M,PATEL H,et al.Novel Siglec-15-Sia axis inhibitor leads to colorectal cancer cell death by targeting miR-6715b-3p and oncogenes [J].Front Immunol,2023,14:1254911.
[17]伍远浩,黄平,李来春.Siglec-15×CD3双特异性抗体通过介导T细胞抗肿瘤免疫抑制结直肠癌细胞生长[J].现代肿瘤医学,2023,31(04):638-643. WU Yuanhao,HUANG Ping,LI Laichun.Siglec-15×CD3 bispecific antibody inhibits colorectal cancer cell growth by mediating T cell anti-tumor immunity [J].Modern Oncology,2019,31(04):638-643.
[18] WANG Y,XU Z,WU KL,et al.Siglec-15/sialic acid axis as a central glyco-immune checkpoint in breast cancer bone metastasis [J].Proc Natl Acad Sci USA,2024,121(5):e2312929121.
[19] LI X,LIANG Z,PAN J,et al.Identification of BACH1-IT2-miR-4786-Siglec-15 immune suppressive axis in bladder cancer [J].BMC Cancer,2024,24(1):328-334.
[20] HEBENSTREIT D,HOREJS-HOECK,DUSCHL A,et al.JAK/STAT-dependent gene regulation by cytokines [J].Drug News & Perspectives,2005,18(4):243-249.
[21] QING Y,STARK GR.Alternative activation of STAT1 and STAT3 in response to interferon-gamma [J].J Biol Chem,2004,279(40):41679-41685.

Memo

Memo:
河南省医学科技攻关计划联合共建项目(编号:LHGJ20230818);河南省洛阳市公益性行业医疗卫生专项(编号:2302040Y)
Last Update: 1900-01-01