TRIM25通过EZH2介导巨噬细胞M2极化促进食管鳞状细胞癌细胞的增殖迁移和侵袭

doi:10.3969/j.issn.1006-6233.2024.03.012

Abstract
Figure/Table
References
Related Citation (13)

Download: PDF (2582 KB) HTML (1 KB)
Export: BibTeX | EndNote (RIS)

Abstract Objective: To explore the roles of TRIM25 and EZH2 in infiltrating macrophages in esophageal squamous cell carcinoma (ESCC) and their potential mechanisms of action.Methods: THP-1 cells were induced to M0 macrophages using phorbol ester, co-cultured with KYSE510 cells after transfection, and the collected co-culture macrophages were divided into Ctrl group, sh-NC group, sh-TRIM25 group, sh-NC+oe-NC group, sh-TRIM25+oe-NC group, sh-NC+oe-EZH2 group, and sh-TRIM25+oe-EZH2 group. The co-culture supernatant was added to KYSE510 cells, and they were divided into Ctrl group, TAM group, sh-NC+TAM group, sh-TRIM25+TAM group, sh-NC+oe-NC+TAM group, sh-TRIM25+oe-NC+TAM group, sh-NC+oe-EZH2+TAM group, and sh-TRIM25+oe-EZH2+TAM group. qPCR and WB were used to detect the expression of TRIM25, EZH2, and Arg-1 in cells. Protein synthesis inhibition experiments were used to test the protein stability of EZH2. FCM was used to detect the proportion of F4/80+CD206+ macrophages. CCK-8, colony formation assay, and Transwell assay were used to evaluate cell proliferation, migration, and invasion. Results: The mRNA and protein expression of TRIM25 and EZH2 in KYSE510 cells were higher than in human esophageal squamous epithelial cells (HET-1A) (P<0.01). Compared with the sh-NC group and sh-NC+oe-NC group, the proportion of F4/80+CD206+ macrophages and the expression of Arg-1 protein in the sh-TRIM25 group and sh-TRIM25+oe-NC group decreased (P<0.05), while it increased in the sh-NC+oe-EZH2 group (P<0.05). Compared with the sh-NC+TAM group and sh-NC+oe-NC+TAM group, the sh-TRIM25+TAM group and sh-TRIM25+oe-NC+TAM group showed decreased KYSE510 cell viability, colony formation, migration, and invasion (P<0.05), while the sh-NC+oe-EZH2+TAM group showed an increase (P<0.05). Knockdown of TRIM25 could inhibit the protein half-life of EZH2. Overexpression of EZH2 partially reversed the effects of sh-TRIM25 on macrophages and KYSE510 cells. Conclusion: TRIM25 induces M2 polarization of macrophages by promoting the stability of EZH2 protein, thereby promoting the proliferation, migration, and invasion of esophageal squamous cell carcinoma cells.

Key words： Esophageal squamous cell carcinoma Triartite motif 25 Ehancer of zeste 2 polycomb repressive complex 2 subunits KYSE510 cell Macrophages

	Service

	E-mail this article
	Add to my bookshelf
	Add to citation manager
	E-mail Alert
	RSS
	Articles by authors
	ZHANG Shitong
	TIAN Xinchun
	HUA Haiyang
	et al

Cite this article:

ZHANG Shitong,TIAN Xinchun,HUA Haiyang, et al. TRIM25 Promotes the Proliferation Migration and Invasion of Esophageal Squamous Cell Carcinoma Cells through EZH2-Mediated Macrophage M2 Polarization[J]. HeBei Med, 2024, 30(3): 416-422.

URL:

http://www.hbyxzzs.cn/EN/10.3969/j.issn.1006-6233.2024.03.012 OR http://www.hbyxzzs.cn/EN/Y2024/V30/I3/416

[1] Short M W,Burgers K G,Fry V T.Esophageal cancer[J].Am Fam Physician,2017,95(1):22-28.
[2] Sawa-wejksza K,Kandefer-szersen M.Tumor-associated macrophages as target for antitumor therapy[J] Arch Immunol Ther Exp (Warsz),2018,66(2):97-111.
[3] Yang K S,Xu C Q,Lv J.Identification and validation of the prognostic value of cyclic GMP-AMP synthase-stimulator of interferon (cGAS-STING) related genes in gastric cancer[J] Bioengineered,2021,12(1):1238-1250.
[4] Yin H L,Wang Y D,Wu Y,et al.EZH2-mediated Epigenetic Silencing of miR-29/miR-30 targets LOXL4 and contributes to tumorigenesis,metastasis,and immune microenvironment remodeling in breast cancer[J] Theranostics,2020,10(19):8494-8512.
[5] Zhou S,Peng J H,Xiao L N,et al.TRIM25 regulates oxaliplatin resistance in colorectal cancer by promoting EZH2 stability[J] Cell Death Dis,2021,12(5):463.
[6] 刘董剑,杨凌.食管鳞状细胞癌研究模型:细胞系、动物移植模型和3D培养模型[J].中国肿瘤生物治疗杂志,2021,28(2):199-210.
[7] Hinshaw D C,Shevde L A.The tumor microenvironment innately modulates cancer progression[J] Cancer Res,2019,79(18):4557-4566.
[8] Bader J E,Voss K,Rathell J C.Targeting metabolism to improve the tumor microenvironment for cancer immunotherapy[J] Mol Cell,2020,78(6):1019-1033.
[9] Mehla K,Singh P K.Metabolic regulation of macrophage polarization in cancer[J] Trends Cancer,2019,5(12):822-834.
[10] Lu Q J,Wang X Y,Zhu J,et al.Hypoxic tumor-derived exosomal Circ0048117 facilitates M2 macrophage polarization acting as miR-140 sponge in esophageal squamous cell carcinoma[J] Onco Targets Ther,2020(13):11883-11897.
[11] Liu Z Y,Wu C,Pan Y Y,et al.NDR2 promotes the antiviral immune response via facilitating TRIM25-mediated RIG-I activation in macrophages[J] Sci Adv,2019,5(2):163.
[12] Eich M L,Athar M,Ferguson J E 3rd,et al.EZH2-targeted therapies in cancer:hype or a reality[J].Cancer Res,2020,80(24):5449-5458.
[13] Zhang M T,Zhang M L,Li R J,et al.Melatonin sensitizes esophageal cancer cells to 5-fluorouracil via promotion of apoptosis by regulating EZH2 expression[J] Oncol Rep,2021,45(4):22.
[14] Neele A E,De winther M P J.Repressing the repressor:Ezh2 mediates macrophage activation[J].Exp Med,2018,215(5):1269-1271.