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

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.