TY  - JOUR
AU  - Zeng, Fanchun
AU  - Zhao, Chunrong
AU  - Wang, Rujie
AU  - Ren, Lingyan
AU  - Qiu, Hao
AU  - Zou, Zhi
AU  - Ding, Haibin
AU  - Sun, Zhongyi
AU  - Li, Jianmei
AU  - Dong, Shiwu
PY  - 2023
TI  - Antagonizing exosomal miR-18a-5p derived from prostate cancer cells ameliorates metastasis-induced osteoblastic lesions by targeting Hist1h2bc and activating Wnt/β-catenin pathway
JO  - Genes & Diseases
SN  - 2352-4820
SP  - 1626
EP  - 1640
VL  - 10
IS  - 4
AB  - 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.
UR  - https://doi.org/10.1016/j.gendis.2022.06.007
DO  - 10.1016/j.gendis.2022.06.007