Biofilm Biomimetic miR-29a Nanoparticles Inhibit Prostate Cancer Progression via Tristetraprolin/HuR-AR

Abstract

Prostate cancer (PCa) occupies the second place among all male malignancies worldwide. Our study explored therapeutic mechanism of biofilm biomimetic nanoparticles encapsulating miR-29a on PCa. The expression and location of HuR and Androgen Receptor (AR) were detected by immunohistochemistry, Western blot and Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) along with analysis of cell apoptosis. After repeated extrusion of nanoparticles, cell membrane fragments were extruded into hollow spherical vesicles of 100–200 nm, which consisted of micron-scale concave disks. In prostate tissue, HuR protein was expressed in both nucleus and cytoplasm, while AR protein was mostly expressed in nucleus. miR-29a and Tristetraprolin (TTP) expressions decreased in LNCaP and DU145 (P < 0.05) while the HuR level increased (P < 0.05) miR-29a targeted TTP. Overexpression of miR-29a upregulated TTP and downregulated HuR (P <0.05), inhibiting miR-29a expression, which decreased TTP and increased the HuR level (P < 0.05). Overexpression of miR-29a inhibited cancer cell activities (P < 0.05) and its inhibition inhibited apoptosis (P <0.05). Biofilm biomimetic nanoparticles encapsulated miR-29a regulated TTP and HuR expression and significantly affected activities of prostate cancer cells, indicating that encapsulation of miR-29a by biofilm biomimetic nanoparticles may become a new way for prostate cancer treatment.