@article{Zeng2023, 
author = {Fanchun Zeng and Chunrong Zhao and Rujie Wang and Lingyan Ren and Hao Qiu and Zhi Zou and Haibin Ding and Zhongyi Sun and Jianmei Li and Shiwu Dong},
title = {Antagonizing exosomal miR-18a-5p derived from prostate cancer cells ameliorates metastasis-induced osteoblastic lesions by targeting Hist1h2bc and activating Wnt/β-catenin pathway},
year = {2023},
journal = {Genes & Diseases},
volume = {10},
number = {4},
pages = {1626-1640},
keywords = {Bone metastasis, MiR-18a-5p, Osteoblastic lesions, Prostate cancer, Wnt/β-catenin pathway},
url = {https://www.sciopen.com/article/10.1016/j.gendis.2022.06.007},
doi = {10.1016/j.gendis.2022.06.007},
abstract = {More than 50% of prostate cancer (PCa) patients have bone metastasis with osteoblastic lesions. MiR-18a-5p is associated with the development and metastasis of PCa, but it remains unclear whether it is involved in osteoblastic lesions. We first found that miR-18a-5p was highly expressed in the bone microenvironment of patients with PCa bone metastases. To address how miR-18a-5p affects PCa osteoblastic lesions, antagonizing miR-18a-5p in PCa cells or pre-osteoblasts inhibited osteoblast differentiation in vitro. Moreover, injection of PCa cells with miR-18a-5p inhibition improved bone biomechanical properties and bone mineral mass in vivo. Furthermore, miR-18a-5p was transferred to osteoblasts by exosomes derived from PCa cells and targeted the Hist1h2bc gene, resulting in Ctnnb1 up-regulation in the Wnt/β-catenin signaling pathway. Translationally, antagomir-18a-5p significantly improved bone biomechanical properties and alleviated sclerotic lesions from osteoblastic metastases in BALB/c nude mice. These data suggest that inhibition of exosome-delivered miR-18a-5p ameliorates PCa-induced osteoblastic lesions.}
}