Yuan Xiaorong, Yang Xuejie
Department of Lymphatic Breast Oncology, Baotou Cancer Hospital, Baotou, 014030, China.
Cell Biochem Biophys. 2025 Jun;83(2):2035-2045. doi: 10.1007/s12013-024-01614-0. Epub 2024 Nov 18.
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.
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.
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.
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.
磷脂磷酸酶4（PLPP4）已被确定为癌细胞动力学的潜在调节因子，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）的敏感性仍不清楚。
本研究采用定量实时逆转录聚合酶链反应（qRT-PCR）和蛋白质免疫印迹分析，分析PLPP4和细胞周期相关蛋白1（CAPRIN1）在BC组织和细胞中的表达。采用集落形成、EdU、Transwell和流式细胞术等功能分析方法评估细胞行为。通过CCK-8分析和体内异种移植模型分析，分析BC细胞对DOX的敏感性。采用RNA免疫沉淀分析和双荧光素酶报告基因分析，研究PLPP4与CAPRIN1之间的关系。
在BC组织和细胞中观察到PLPP4表达上调。BC细胞中PLPP4表达下调导致其增殖能力受到抑制，迁移和侵袭能力降低。此外，这种操作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。当在可移植肿瘤体内敲低PLPP4时，对DOX治疗的反应性显著增强。发现转录因子CAPRIN1在HCC1937和MDA-MB-231细胞系中调节PLPP4的表达。在BC组织和细胞中均观察到CAPRIN1上调，PLPP4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通过转录激活PLPP4来抑制DOX敏感性并促进BC进展。靶向PLPP4可能代表一种新的治疗策略，以提高DOX对BC患者的疗效。
