Integrated transcriptomic and functional analyses identify PRR7 as a therapeutic target that associated with Wnt/β-catenin signaling and docetaxel resistance in prostate cancer.

Authors

Wei Sun, Yuheng Si, Lu Hong, Qingxiang Guo, Zhihui Lu, Antao Dong, Yurui Tang, Enlai Li, Wei He, Shiyao Feng, Dongdong Xie

Published in

Biochemical and biophysical research communications. Volume 832. Pages 154364. Jul 29, 2026. Epub Jul 29, 2026.

Abstract

Docetaxel resistance represents a major therapeutic challenge in advanced prostate cancer. Despite extensive studies on drug efflux, apoptosis, and metabolic adaptation, the specific cellular states and molecular determinants that sustain resistance remain poorly understood.
To delineate the cellular basis of chemoresistance, we integrated bulk RNA sequencing of docetaxel-resistant prostate cancer models with single-cell transcriptomic data from patient tumors. Resistance-associated gene signatures were projected onto a single-cell atlas to identify docetaxel-resistant associated cancer cells (DRACs). Candidate regulators were screened through cross-dataset analysis and validated using molecular, cellular, and organoid-based assays, with functional and signaling consequences evaluated across in vitro and in vivo systems.
Single-cell mapping revealed a distinct epithelial cluster characterized by enrichment of resistance-related transcriptional programs and extensive communication with stromal cells. Integrative analyses identified PRR7 as a consistently upregulated gene within DRACs and resistant cell lines. PRR7 amplification and co-alteration with PI3K-AKT and Wnt pathway components were observed in clinical datasets. Functional inhibition of PRR7 suppressed β-catenin signaling, reduced cell viability, and downregulated stemness markers in docetaxel-resistant cells and patient-derived organoids. These results support a functional association between PRR7 and Wnt/β-catenin-related maintenance of resistance.
The study defines DRACs as a transcriptionally distinct subpopulation sustaining docetaxel tolerance and identifies PRR7 as a regulatory hub connecting genomic alterations, Wnt/β-catenin activation, and stem-like phenotypes. These findings provide a framework for understanding chemoresistance in prostate cancer and suggest PRR7-centered signaling as a potential target for therapeutic intervention.

PMID:
42542043
Bibliographic data and abstract were imported from PubMed on 02 Aug 2026.

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