Tumor Cell-Derived Complement Component C1r Acts as a Prognostic Biomarker and Promotes Esophageal Squamous Cell Carcinoma Progression

IF 3.1 4区生物学 Q2 Immunology and Microbiology

Frontiers in Bioscience-Landmark Pub Date : 2024-04-02 DOI:10.31083/j.fbl2904138

Maolin Tang, Shisheng Zhao, Ling Ren, Qianqian Li, Li Li, Chaoli Wang, Chunmei Meng, Yuling Chen, Weimin Hu

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引用次数: 0

Abstract

Background : Mounting evidence indicates that complement components play a crucial role in cancer progression. Recent findings indicate that certain complement components display a significant rise in expression within esophageal squamous cell carcinoma (ESCC). However, the specific tumorigenic functions of these components remain unclear. This study focuses on investigating the expression pattern of C1r, elucidating a role for C1r in ESCC, as well as exploring underlying mechanisms controlled by C1r. Methods : The expression of C1r in ESCC tissues, malignant epithelial cells, and its relationship with survival were analyzed using the Gene Expression Omnibus (GEO) database and tissue microarrays. Single-cell RNA sequencing (scRNA-seq) was used to study the expression of C1r in malignant epithelial cells. C1r knockdown or C1r overexpression in cultured ESCC cells were used to assess the effects of C1r on proliferation, migration, invasion, cell-matrix adhesion, apoptosis, and growth of xenografted tumors in immunocompromised (nude) mice. Western blotting was used to detect the expression of MMP-1 and MMP-10 in C1r knockdown or C1r overexpressing ESCC cells. Results : C1r was highly expressed in ESCC tissues, malignant epithelial cells, and cultured ESCC cell lines. High C1r expression indicated a poor prognosis. Knockdown of C1r significantly suppressed the proliferation, migration, invasion, cell-matrix adhesion, and promoted apoptosis in cultured ESCC cells. Additionally, knockdown of C1r markedly inhibited tumor growth in nude mice. Overexpression of C1r had the opposite effects. C1r induced the expression of MMP-1 and MMP-10. Conclusions : C1r is highly expressed in ESCC and promotes the progression of this tumor type. Our findings suggest that C1r may serve as a novel prognostic biomarker and therapeutic target in ESCC.

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肿瘤细胞衍生的补体成分 C1r 可作为预后生物标记物并促进食管鳞状细胞癌的进展

背景：越来越多的证据表明，补体成分在癌症进展中起着至关重要的作用。最近的研究结果表明，某些补体成分在食管鳞状细胞癌（ESCC）中的表达明显升高。然而，这些成分的具体致癌功能仍不清楚。本研究重点研究C1r的表达模式，阐明C1r在ESCC中的作用，并探索C1r控制的潜在机制。方法：利用基因表达总库（GEO）数据库和组织芯片分析C1r在ESCC组织、恶性上皮细胞中的表达及其与存活率的关系。单细胞 RNA 测序（scRNA-seq）用于研究 C1r 在恶性上皮细胞中的表达。在培养的 ESCC 细胞中敲除 C1r 或过表达 C1r，以评估 C1r 对免疫缺陷（裸鼠）小鼠异种移植肿瘤的增殖、迁移、侵袭、细胞-基质粘附、凋亡和生长的影响。用 Western 印迹法检测 C1r 基因敲除或 C1r 基因过表达 ESCC 细胞中 MMP-1 和 MMP-10 的表达。结果：C1r 在 ESCC 组织、恶性上皮细胞和培养的 ESCC 细胞系中高表达。C1r的高表达表明预后不良。敲除 C1r 能显著抑制 ESCC 细胞的增殖、迁移、侵袭、细胞与基质的粘附，并促进细胞凋亡。此外，敲除 C1r 还能明显抑制肿瘤在裸鼠体内的生长。过表达 C1r 则会产生相反的效果。C1r 可诱导 MMP-1 和 MMP-10 的表达。结论：C1r 在 ESCC 中高度表达，并促进该肿瘤类型的进展。我们的研究结果表明，C1r 可作为 ESCC 的新型预后生物标志物和治疗靶点。

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来源期刊

Frontiers in Bioscience-Landmark 生物-生化与分子生物学

CiteScore

3.40

自引率

3.20%

发文量

301

审稿时长

3 months

期刊介绍： FBL is an international peer-reviewed open access journal of biological and medical science. FBL publishes state of the art advances in any discipline in the area of biology and medicine, including biochemistry and molecular biology, parasitology, virology, immunology, epidemiology, microbiology, entomology, botany, agronomy, as well as basic medicine, preventive medicine, bioinformatics and other related topics.