The Dual Role of RBBP7 in Esophageal Squamous Cell Carcinoma: Cell Context-Dependent Impacts on Proliferation and Radiosensitivity.

IF 2.8 4区医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

OncoTargets and therapy Pub Date : 2025-09-04 eCollection Date: 2025-01-01 DOI:10.2147/OTT.S535750

Yafen Li, Shuai Lu, Hui Yao, Genbao Zhu, Hao Liu, Zhiyu Ma, Heng Tang

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引用次数: 0

Abstract

Background: Radiotherapy resistance contributes to poor prognosis in esophageal squamous cell carcinoma (ESCC). Retinoblastoma-binding protein 7 (RBBP7) is a nuclear protein, and it can promote or inhibit tumor progression in cancer, but its function in ESCC cells and impact on radiosensitivity remains unclear.

Methods: RBBP7 expression in cancer was analyzed using an online website. The expression levels of RBBP7 in ESCC cells (TE-1 and KYSE-150) and tissues were tested. Cells were subjected to RBBP7 gene silencing and irradiation (IR). Assays included CCK-8, clonogenic survival, flow cytometry (apoptosis/cell cycle), ROS detection, and Western blotting for DNA damage (γ-H2AX) and STAT3 signaling. Additionally, pathological tissue specimens and clinical data from ESCC patients were used to explore the expression of RBBP7.and its relationship with the clinical parameters of patients.

Results: RBBP7 was overexpressed in malignant tumors. In ESCC cells, the mRNA and protein of RBBP7 were also highly expressed. After silencing RBBP7 combined with IR treatment, contradictory effects were observed between cell lines: In well-differentiated TE-1 cells, RBBP7 knockdown suppressed proliferation, enhanced radiosensitivity (SER=1.370), increased ROS/DNA damage (γ-H2AX), promoted apoptosis, and reduced STAT3 activation (possibly through STAT3 signaling). In poorly-differentiated KYSE-150 cells, knockdown promoted proliferation, decreased radiosensitivity (SER=0.775), reduced apoptosis, and increased p-STAT3. In addition, knockdown caused S-phase arrest (TE-1) versus G0/G1 arrest (KYSE-150), with divergent CDK4/Cyclin D1 regulation. Clinical analysis confirmed RBBP7 positivity correlated with tumor differentiation, TNM stage, and radiotherapy method.

Conclusion: RBBP7 is highly expressed in ESCC, and it exerts cell context-dependent dual roles in ESCC, leading to differences in cellular radiosensitivity, possibly mediated through STAT3 signaling. This dichotomy highlights its potential as a differentiation status-specific therapeutic target.

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RBBP7在食管鳞状细胞癌中的双重作用：细胞环境依赖性对增殖和放射敏感性的影响

背景：放疗抵抗是食管鳞状细胞癌（ESCC）预后不良的原因之一。视网膜母细胞瘤结合蛋白7 （Retinoblastoma-binding protein 7, RBBP7）是一种核蛋白，在癌症中可促进或抑制肿瘤进展，但其在ESCC细胞中的功能及其对放射敏感性的影响尚不清楚。方法：利用在线网站分析RBBP7在肿瘤组织中的表达。检测RBBP7在ESCC细胞（TE-1和KYSE-150）及组织中的表达水平。细胞接受RBBP7基因沉默和辐照（IR）。检测包括CCK-8、克隆存活、流式细胞术（凋亡/细胞周期）、ROS检测和DNA损伤（γ-H2AX）和STAT3信号的Western blotting。此外，我们还利用ESCC患者的病理组织标本和临床资料来探讨RBBP7的表达。及其与患者临床参数的关系。结果：RBBP7在恶性肿瘤中过表达。在ESCC细胞中，RBBP7的mRNA和蛋白也高表达。RBBP7沉默联合IR处理后，在细胞系之间观察到矛盾的效应：在分化良好的TE-1细胞中，RBBP7敲低抑制增殖，增强放射敏感性（SER=1.370），增加ROS/DNA损伤（γ-H2AX），促进细胞凋亡，减少STAT3激活（可能通过STAT3信号传导）。在低分化的KYSE-150细胞中，敲低促进了增殖，降低了放射敏感性（SER=0.775），减少了凋亡，增加了p-STAT3。此外，敲低引起s期阻滞（TE-1）和G0/G1阻滞（KYSE-150），具有不同的CDK4/Cyclin D1调控。临床分析证实RBBP7阳性与肿瘤分化、TNM分期及放疗方式相关。结论：RBBP7在ESCC中高表达，并在ESCC中发挥细胞环境依赖的双重作用，导致细胞放射敏感性的差异，可能通过STAT3信号通路介导。这种二分法突出了其作为分化状态特异性治疗靶点的潜力。

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

OncoTargets and therapy BIOTECHNOLOGY & APPLIED MICROBIOLOGY-ONCOLOGY

CiteScore

9.70

自引率

0.00%

发文量

221

审稿时长

1 months

期刊介绍： OncoTargets and Therapy is an international, peer-reviewed journal focusing on molecular aspects of cancer research, that is, the molecular diagnosis of and targeted molecular or precision therapy for all types of cancer. The journal is characterized by the rapid reporting of high-quality original research, basic science, reviews and evaluations, expert opinion and commentary that shed novel insight on a cancer or cancer subtype. Specific topics covered by the journal include: -Novel therapeutic targets and innovative agents -Novel therapeutic regimens for improved benefit and/or decreased side effects -Early stage clinical trials Further considerations when submitting to OncoTargets and Therapy: -Studies containing in vivo animal model data will be considered favorably. -Tissue microarray analyses will not be considered except in cases where they are supported by comprehensive biological studies involving multiple cell lines. -Biomarker association studies will be considered only when validated by comprehensive in vitro data and analysis of human tissue samples. -Studies utilizing publicly available data (e.g. GWAS/TCGA/GEO etc.) should add to the body of knowledge about a specific disease or relevant phenotype and must be validated using the authors’ own data through replication in an independent sample set and functional follow-up. -Bioinformatics studies must be validated using the authors’ own data through replication in an independent sample set and functional follow-up. -Single nucleotide polymorphism (SNP) studies will not be considered.