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PDLIM1 是一个新的 miR-3940-5p 靶标,调节弥漫性大 B 细胞淋巴瘤的恶性进展。

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

机构信息

Department of Oncology, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, China.

Department of Hematology, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, Fujian Province, China.

出版信息

Cancer Biol Ther. 2024 Dec 31;25(1):2429175. doi: 10.1080/15384047.2024.2429175. Epub 2024 Nov 20.

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 and .

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.

摘要

背景

PDZ 和 LIM 结构域蛋白 1(PDLIM1)是一种蛋白编码基因,已广泛报道其在多种人类癌症中表现出差异表达模式,包括血液恶性肿瘤。本研究旨在探讨 PDLIM1 在弥漫性大 B 细胞淋巴瘤(DLBCL)中的表达模式及其功能作用。

方法

使用基因表达综合数据库中的数据重新分析 PDLIM1 的表达模式,并随后在患者组织样本和四个 DLBCL 细胞系中验证结果。miR-3940-5p(miR-3940-5p)被鉴定为 PDLIM1 的上游调节因子。进一步使用 DLBCL 小鼠模型探索 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。敲低该基因后观察到细胞增殖减少和 DLBCL 细胞凋亡增加。此外,短发夹 RNA(shRNA)介导的 PDLIM1 敲低可减少裸鼠中 DLBCL 细胞的肿瘤发生。miR-3940-5p 被鉴定为 PDLIM1 的上游调节因子。miR-3940-5p 的上调负调控 PDLIM1 的表达和功能,从而影响 DLBCL 细胞的恶性表型。

结论

这些发现表明,miR-3940-5p/PDLIM1 轴可能在 DLBCL 发病机制中发挥关键作用,并可能被用于治疗干预。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8f6/11581179/81f6abcb7864/KCBT_A_2429175_F0001_OC.jpg

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