Targeting the HSP60/p53 Axis with Extracellular Vesicle-Delivered siRNA Reprograms Glycolysis in Prostate Cancer

Area of Science:

• Oncology
• Molecular Biology
• Biotechnology

Background:

• Prostate cancer (PCa) presents a significant therapeutic challenge due to limited targeted treatment options.
• Heat shock protein 60 (HSP60), encoded by *HSPD1*, is implicated in cancer progression.

Purpose of the Study:

• To investigate the oncogenic role of HSP60 in PCa.
• To develop siRNA-loaded extracellular vesicles (siRNA@EVs) for targeted PCa therapy by silencing *HSPD1*.

Main Methods:

• Bioinformatic analysis (*HSPD1* expression in PCa).
• Validation using qPCR and Western blot.
• Metabolomic-transcriptomic integration and molecular assays.
• siRNA@EVs construction and evaluation *in vitro* and *in vivo* (xenograft models).

Main Results:

• *HSPD1* is overexpressed in PCa, correlating with advanced disease and poor prognosis.
• HSP60 promotes PCa proliferation, metastasis, and tumor growth by enhancing glycolysis via p53 suppression.
• *HSPD1* knockdown via siRNA@EVs effectively inhibited PCa cell proliferation, metastasis, and xenograft tumor growth with demonstrated safety.

Conclusions:

• HSP60 plays a crucial role in PCa metabolic reprogramming and oncogenesis.
• siRNA@EVs targeting *HSPD1* represent a promising, safe, and effective precision therapy for prostate cancer.