PDLIM1, a novel miR-3940-5p target, regulates the malignant progression of diffuse large B-cell lymphoma.

IF 4.4 4区医学 Q2 ONCOLOGY Cancer Biology & Therapy Pub Date : 2024-12-31 Epub Date: 2024-11-20 DOI:10.1080/15384047.2024.2429175

Jinfeng Zhu, Huifang Xiao, Chuntuan Li, Xiaofeng Li, Jinyang Zheng, Xihu Yao, Shaoxiong Wang, Xiongpeng Zhu

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Abstract

Background: PDZ And LIM domain protein 1 (PDLIM1), a protein-coding gene, has been widely reported to exhibit differential expression patterns across various human cancers, including hematological malignancies. This study aimed to investigate PDLIM1 expression pattern and its functional role in diffuse large B-cell lymphoma (DLBCL) both in vitro and in vivo.

Methods: PDLIM1 expression patterns were reanalyzed using data from the Gene Expression Omnibus, and the results were subsequently validated in patient tissue samples and a panel of four DLBCL cell lines. MicroRNA-3940-5p (miR-3940-5p) was identified as an upstream regulator of PDLIM1. The interaction between PDLIM1 and miR-3940-5p and its effects on DLBCL cellular activities and cancer development were further explored using a DLBCL mouse model.

Results: Elevated PDLIM1 expression was observed in DLBCL cells and tissues. Reduced cell proliferation and increased DLBCL cell apoptosis were observed following the knockdown of this gene. Furthermore, short hairpin RNA (shRNA)-mediated PDLIM1 knockdown diminished tumorigenesis of DLBCL cells in nude mice. miR-3940-5p was identified as an upstream regulator of PDLIM1. PDLIM1 expression and function were negatively modulated by the upregulation of miR-3940-5p, consequently affecting the malignant phenotype of DLBCL cells.

Conclusion: These findings suggest that the miR-3940-5p/PDLIM1 axis may play a crucial role in DLBCL pathogenesis and could potentially be exploited for therapeutic interventions.

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新型 miR-3940-5p 靶点 PDLIM1 可调控弥漫大 B 细胞淋巴瘤的恶性进展。

背景：PDZ 和 LIM 结构域蛋白 1（PDLIM1）是一种蛋白编码基因，已被广泛报道在包括血液恶性肿瘤在内的各种人类癌症中表现出不同的表达模式。本研究旨在研究 PDLIM1 在弥漫大 B 细胞淋巴瘤（DLBCL）中的体外和体内表达模式及其功能作用：方法：利用基因表达总库（Gene Expression Omnibus）中的数据重新分析了PDLIM1的表达模式，随后在患者组织样本和四种DLBCL细胞系中验证了结果。微RNA-3940-5p（miR-3940-5p）被确定为PDLIM1的上游调节因子。利用DLBCL小鼠模型进一步探讨了PDLIM1和miR-3940-5p之间的相互作用及其对DLBCL细胞活性和癌症发展的影响：结果：在DLBCL细胞和组织中观察到PDLIM1表达升高。结果：在 DLBCL 细胞和组织中观察到 PDLIM1 表达升高，敲除该基因后细胞增殖减少，DLBCL 细胞凋亡增加。此外，短发夹核糖核酸（shRNA）介导的 PDLIM1 基因敲除减少了裸鼠 DLBCL 细胞的肿瘤发生。PDLIM1的表达和功能受miR-3940-5p上调的负调控，从而影响DLBCL细胞的恶性表型：这些研究结果表明，miR-3940-5p/PDLIM1 轴可能在 DLBCL 发病机制中起着关键作用，有可能被用于治疗干预。

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 Biology & Therapy 医学-肿瘤学

CiteScore

7.00

自引率

0.00%

发文量

审稿时长

2.3 months

期刊介绍： Cancer, the second leading cause of death, is a heterogenous group of over 100 diseases. Cancer is characterized by disordered and deregulated cellular and stromal proliferation accompanied by reduced cell death with the ability to survive under stresses of nutrient and growth factor deprivation, hypoxia, and loss of cell-to-cell contacts. At the molecular level, cancer is a genetic disease that develops due to the accumulation of mutations over time in somatic cells. The phenotype includes genomic instability and chromosomal aneuploidy that allows for acceleration of genetic change. Malignant transformation and tumor progression of any cell requires immortalization, loss of checkpoint control, deregulation of growth, and survival. A tremendous amount has been learned about the numerous cellular and molecular genetic changes and the host-tumor interactions that accompany tumor development and progression. It is the goal of the field of Molecular Oncology to use this knowledge to understand cancer pathogenesis and drug action, as well as to develop more effective diagnostic and therapeutic strategies for cancer. This includes preventative strategies as well as approaches to treat metastases. With the availability of the human genome sequence and genomic and proteomic approaches, a wealth of tools and resources are generating even more information. The challenge will be to make biological sense out of the information, to develop appropriate models and hypotheses and to translate information for the clinicians and the benefit of their patients. Cancer Biology & Therapy aims to publish original research on the molecular basis of cancer, including articles with translational relevance to diagnosis or therapy. We will include timely reviews covering the broad scope of the journal. The journal will also publish op-ed pieces and meeting reports of interest. The goal is to foster communication and rapid exchange of information through timely publication of important results using traditional as well as electronic formats. The journal and the outstanding Editorial Board will strive to maintain the highest standards for excellence in all activities to generate a valuable resource.