Unveiling CKS2: A Key Player in Aggressive B-Cell Lymphoma Progression and a Target for Synergistic Therapy

IF 2.9 2区医学 Q2 ONCOLOGY

Cancer Medicine Pub Date : 2024-11-19 DOI:10.1002/cam4.70435

Fenling Zhou, Lu Chen, Zhen Liu, Yuli Cao, Cuilan Deng, Gexiu Liu, Chengcheng Liu

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引用次数: 0

Abstract

Background

The objective of this study was to investigate the expression levels and biological significance of CKS2 in Burkitt cell lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL). Additionally, the potential synergistic anti-tumor effects of CKS2 knockdown in combination with etoposide in BL and DLBCL were explored for the first time.

Methods

Bioinformatics analysis was utilized to explore the transcriptional levels, prognostic value, and gene function enrichment of CKS2 in BL and DLBCL. Specific shRNA sequences were designed to target CKS2 for the purpose of constructing a lentiviral expression vector, and therapeutic effects were assessed through analyses of cell proliferation, cell cycle distribution, and cell apoptosis.

Results

First, the study examined the increased transcriptional and protein levels of CKS2 in BL and DLBCL through analysis of various databases and immunohistochemistry tests. Elevated CKS2 expression was found to be correlated with a worse prognosis in BL and DLBCL patients, as evidenced by data from the TCGA and GEO databases. Enrichment analysis indicated that CKS2 functions were primarily linked to protein kinase regulatory activity, G1/S phase transition of the cell cycle, and the p53 signaling pathway, among others. Second, stable suppression of CKS2 gene expression in Raji and SUDHL6 cells using shRNA resulted in a significant inhibition of cell proliferation. Moreover, CKS2-shRNA induced G0/G1 cell cycle arrest and apoptosis by activating the p53 signaling pathway in Raji and SUDHL6 cells. Third, the combined treatment of CKS2-shRNA and etoposide exhibited a synergistic effect on the proliferation and apoptosis of Raji and SUDHL6 cells.

Conclusions

Our findings suggest that CKS2 may play a critical role in the progression of BL and DLBCL and provide evidence for the potential therapeutic application of combining CKS2-shRNA and etoposide agents in the treatment of BL and DLBCL.

Abstract Image

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揭开 CKS2 的神秘面纱：侵袭性 B 细胞淋巴瘤发展过程中的关键角色和协同治疗的靶点。

研究背景本研究旨在探讨CKS2在伯基特细胞淋巴瘤（BL）和弥漫大B细胞淋巴瘤（DLBCL）中的表达水平和生物学意义。此外，研究还首次探讨了在BL和DLBCL中敲除CKS2与依托泊苷联合使用的潜在协同抗肿瘤效应：方法：利用生物信息学分析探讨CKS2在BL和DLBCL中的转录水平、预后价值和基因功能富集。为了构建慢病毒表达载体，研究人员设计了针对CKS2的特定shRNA序列，并通过分析细胞增殖、细胞周期分布和细胞凋亡评估了治疗效果：首先，研究通过分析各种数据库和免疫组化检测，检测了CKS2在BL和DLBCL中转录和蛋白水平的升高。TCGA和GEO数据库的数据显示，CKS2表达的升高与BL和DLBCL患者预后的恶化相关。富集分析表明，CKS2的功能主要与蛋白激酶调控活性、细胞周期的G1/S期转变和p53信号通路等有关。其次，利用 shRNA 稳定抑制 Raji 和 SUDHL6 细胞中 CKS2 基因的表达可显著抑制细胞增殖。此外，CKS2-shRNA 通过激活 Raji 和 SUDHL6 细胞的 p53 信号通路，诱导 G0/G1 细胞周期停滞和细胞凋亡。第三，CKS2-shRNA 和依托泊苷联合处理对 Raji 和 SUDHL6 细胞的增殖和凋亡有协同作用：我们的研究结果表明，CKS2可能在BL和DLBCL的发展过程中起着关键作用，并为CKS2-shRNA和依托泊苷联合治疗BL和DLBCL的潜在治疗应用提供了证据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer Medicine ONCOLOGY-

CiteScore

5.50

自引率

2.50%

发文量

907

审稿时长

19 weeks

期刊介绍： Cancer Medicine is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research from global biomedical researchers across the cancer sciences. The journal will consider submissions from all oncologic specialties, including, but not limited to, the following areas: Clinical Cancer Research Translational research ∙ clinical trials ∙ chemotherapy ∙ radiation therapy ∙ surgical therapy ∙ clinical observations ∙ clinical guidelines ∙ genetic consultation ∙ ethical considerations Cancer Biology: Molecular biology ∙ cellular biology ∙ molecular genetics ∙ genomics ∙ immunology ∙ epigenetics ∙ metabolic studies ∙ proteomics ∙ cytopathology ∙ carcinogenesis ∙ drug discovery and delivery. Cancer Prevention: Behavioral science ∙ psychosocial studies ∙ screening ∙ nutrition ∙ epidemiology and prevention ∙ community outreach. Bioinformatics: Gene expressions profiles ∙ gene regulation networks ∙ genome bioinformatics ∙ pathwayanalysis ∙ prognostic biomarkers. Cancer Medicine publishes original research articles, systematic reviews, meta-analyses, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented in the paper.