CAPRIN1 Transcriptionally Activated PLPP4 to Inhibit DOX Sensitivity and Promote Breast Cancer Progression.

IF 1.8 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Cell Biochemistry and Biophysics Pub Date : 2024-11-18 DOI:10.1007/s12013-024-01614-0

Xiaorong Yuan, Xuejie Yang

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Abstract

Background: Phospholipid phosphatase 4 (PLPP4) has been identified as a potential regulator of cancer cell dynamics, however, the role of PLPP4 in breast cancer (BC) progression and the sensitivity of BC cells to doxorubicin (DOX) remain elusive.

Methods: The study analyzed the expression of PLPP4 and cell cycle-associated protein 1 (CAPRIN1) expression in BC tissues and cells using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) and western blotting assays. Functional assays including colony formation, EdU, Transwell, and flow cytometry were employed to assess cellular behaviors. The sensitivity of BC cells to DOX was analyzed by CCK-8 assay and an in vivo xenograft model assay. The association between PLPP4 and CAPRIN1 was investigated using RNA immunoprecipitation assay and dual-luciferase reporter assay.

Results: Upregulation of PLPP4 expression was observed in BC tissues and cells. Downregulation of PLPP4 expression in BC cells resulted in a suppression of their proliferative capacity, as well as a reduction in migratory and invasive capabilities. Additionally, this manipulation enhanced cell susceptibility to apoptosis and improved the sensitivity of these cells to DOX. When PLPP4 was knocked down in vivo in transplantable tumors, there was a marked enhancement in the responsiveness to DOX treatment. The transcription factor CAPRIN1 was found to regulate the expression of PLPP4 in the HCC1937 and MDA-MB-231 cell lines. Upregulation of CAPRIN1 was observed in both BC tissues and cells, and overexpression of PLPP4 reversed the effects of CAPRIN1 silencing on BC cell proliferation, migration, invasion, apoptosis, and DOX sensitivity.

Conclusion: This study demonstrates that CAPRIN1 transcriptionally activates PLPP4 to inhibit DOX sensitivity and promote BC progression. Targeting PLPP4 may represent a novel therapeutic strategy to enhance the efficacy of DOX in BC patients.

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CAPRIN1 转录激活 PLPP4 抑制 DOX 敏感性并促进乳腺癌进展

背景：然而，PLPP4在乳腺癌（BC）进展中的作用以及BC细胞对多柔比星（DOX）的敏感性仍未确定：研究采用实时逆转录聚合酶链反应（qRT-PCR）和免疫印迹法分析了PLPP4和细胞周期相关蛋白1（CAPRIN1）在乳腺癌组织和细胞中的表达。功能测定包括集落形成、EdU、Transwell和流式细胞术，用于评估细胞行为。通过 CCK-8 试验和体内异种移植模型试验分析了 BC 细胞对 DOX 的敏感性。利用RNA免疫沉淀实验和双荧光素酶报告实验研究了PLPP4和CAPRIN1之间的关联：结果：在 BC 组织和细胞中观察到 PLPP4 表达上调。在 BC 细胞中下调 PLPP4 的表达可抑制其增殖能力，并降低其迁移和侵袭能力。此外，这种操作还增强了细胞对凋亡的敏感性，并提高了这些细胞对 DOX 的敏感性。在可移植肿瘤体内敲除 PLPP4 后，细胞对 DOX 治疗的反应性明显增强。研究发现，转录因子 CAPRIN1 可调节 PLPP4 在 HCC1937 和 MDA-MB-231 细胞系中的表达。在 BC 组织和细胞中都观察到了 CAPRIN1 的上调，PLPP4 的过表达逆转了 CAPRIN1 沉默对 BC 细胞增殖、迁移、侵袭、凋亡和 DOX 敏感性的影响：本研究表明，CAPRIN1可转录激活PLPP4，从而抑制DOX敏感性并促进BC进展。以 PLPP4 为靶点可能是提高 DOX 对 BC 患者疗效的一种新型治疗策略。

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来源期刊

Cell Biochemistry and Biophysics 生物-生化与分子生物学

CiteScore

4.40

自引率

0.00%

发文量

审稿时长

7.5 months

期刊介绍： Cell Biochemistry and Biophysics (CBB) aims to publish papers on the nature of the biochemical and biophysical mechanisms underlying the structure, control and function of cellular systems The reports should be within the framework of modern biochemistry and chemistry, biophysics and cell physiology, physics and engineering, molecular and structural biology. The relationship between molecular structure and function under investigation is emphasized. Examples of subject areas that CBB publishes are: · biochemical and biophysical aspects of cell structure and function; · interactions of cells and their molecular/macromolecular constituents; · innovative developments in genetic and biomolecular engineering; · computer-based analysis of tissues, cells, cell networks, organelles, and molecular/macromolecular assemblies; · photometric, spectroscopic, microscopic, mechanical, and electrical methodologies/techniques in analytical cytology, cytometry and innovative instrument design For articles that focus on computational aspects, authors should be clear about which docking and molecular dynamics algorithms or software packages are being used as well as details on the system parameterization, simulations conditions etc. In addition, docking calculations (virtual screening, QSAR, etc.) should be validated either by experimental studies or one or more reliable theoretical cross-validation methods.