KNTC1 作为一种潜在的生物标志物和癌基因，调节胃癌中的增殖、迁移和凋亡。

KNTC1 functions as a potential biomarker and oncogene regulating proliferation, migration and apoptosis in gastric cancer.

机构信息

Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan Province 450001, PR China.

Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan Province 450001, PR China; Collaborative Innovation Center of Henan Province for Cancer Chemoprevention, Zhengzhou University, Zhengzhou, Henan Province 450001, PR China; State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan Province 450052, PR China.

出版信息

Int Immunopharmacol. 2024 Dec 25;143(Pt 1):113257. doi: 10.1016/j.intimp.2024.113257. Epub 2024 Oct 2.

DOI:10.1016/j.intimp.2024.113257

PMID:39362011

Abstract

BACKGROUND

As one of the most prevalent cancers, gastric cancer (GC) exhibits a remarkably high morbidity and mortality rate. To date, effective diagnostic and prognostic markers and therapeutic targets for GC are still lacking. Kinetochore associated 1 (KNTC1) is one of the proteins involved in chromosome segregation. However, the diagnostic and prognostic value of KNTC1 and its biological function in GC remain unknown.

METHODS

In this study, Gene Expression Omnibus (GEO) datasets were utilized to identify differentially expressed genes (DEGs). Prognostic and diagnostic value were assessed by Kaplan-Meier plotter and receiver operating characteristic (ROC) curve. The expression of KNTC1 was verified by q-PCR, immunohistochemistry (IHC) and Western blotting. Subsequently, KNTC1 knockdown was employed to investigate its effect on GC cells. Gene set enrichment analysis (GSEA) revealed a pathway regulated by KNTC1, which was further verified by Western blotting.

RESULTS

Four highly expressed genes (ESPL1, RAD54L, KNTC1, TACC3) were identified as biomarkers for GC diagnosis and prognosis. Notably, the value of KNTC1 as a biomarker for GC was newly revealed. Single-cell and immune analyses revealed that KNTC1 contributed to the suppression of the GC immune microenvironment. In clinical samples, we demonstrated high expression of KNTC1 in GC tissues. KNTC1 knockdown suppressed proliferation and migration while promoting apoptosis of GC cells. Additionally, KNTC1 may affect GC cells by regulating the PI3K/Akt/mTOR pathway.

CONCLUSIONS

KNTC1 acts as a potential diagnostic and prognostic marker for GC. It may promote proliferation and migration while inhibiting apoptosis of GC cells via the PI3K/Akt/mTOR pathway.

摘要

背景

胃癌（GC）作为最常见的癌症之一，具有极高的发病率和死亡率。迄今为止，GC 仍然缺乏有效的诊断和预后标志物以及治疗靶点。着丝粒相关蛋白 1（KNTC1）是参与染色体分离的蛋白质之一。然而，KNTC1 的诊断和预后价值及其在 GC 中的生物学功能尚不清楚。

方法

本研究利用基因表达综合数据库（GEO）数据集鉴定差异表达基因（DEGs）。通过 Kaplan-Meier 生存分析和受试者工作特征（ROC）曲线评估预后和诊断价值。通过 q-PCR、免疫组织化学（IHC）和 Western blot 验证 KNTC1 的表达。随后，采用 KNTC1 敲低技术研究其对 GC 细胞的影响。基因集富集分析（GSEA）揭示了 KNTC1 调控的通路，进一步通过 Western blot 进行验证。

结果

鉴定出 4 个高表达基因（ESPL1、RAD54L、KNTC1、TACC3）作为 GC 诊断和预后的生物标志物。值得注意的是，KNTC1 作为 GC 生物标志物的价值是新发现的。单细胞和免疫分析表明，KNTC1 有助于抑制 GC 免疫微环境。在临床样本中，我们证实 GC 组织中 KNTC1 高表达。KNTC1 敲低抑制 GC 细胞的增殖和迁移，同时促进其凋亡。此外，KNTC1 可能通过调节 PI3K/Akt/mTOR 通路影响 GC 细胞。