Ugonin inhibits chondrosarcoma metastasis through suppressing cathepsin V via promoting miR-4799-5p expression

Ugonin 通过促进 miR-4799-5p 表达抑制组织蛋白酶 V 来抑制软骨肉瘤转移

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作者:Nguyen Bao Tran, Ting-Kuo Chang, Nguyen Duong Phuong Chi, Kuan-Ying Lai, Hsien-Te Chen, Yi-Chin Fong, Chih-Chuang Liaw, Chih-Hsin Tang2

Abstract

Chondrosarcoma is a rare type of bone cancer that develops in cartilage cells. In recent years, the incidence of chondrosarcomas has steadily increased worldwide. During the advanced stages, chondrosarcoma carries a significant risk of metastasis and exhibits resistance to both chemotherapy and radiation therapy. Hence, the development of potent treatments for chondrosarcoma is an urgent requirement. Ugonin V is a flavonoid compound that has been extracted from the plant Helminthostachys zeylanica (L.) Hook. This study examined the molecular therapeutic effects of ugonin V on chondrosarcoma metastasis. Analysis of the GSE30835 dataset, which consists of chondrosarcoma tissues and normal cartilage, revealed significant upregulation of three cathepsin proteases in chondrosarcoma, namely cathepsin (CTS) A, L, and V. Notably, ugonin V specifically suppressed cathepsin V mRNA expression. We also found that ugonin V strongly inhibits chondrosarcoma cell motility by regulating CTSV expression. In addition, through miRNA sequencing, we observed that ugonin V targets CTSV via miR-4799-5p to effectively suppress chondrosarcoma cell migration and invasion. Our in vitro and in vivo studies provide an initial investigation of the involvement of cathepsin V and miR-4799-5p in chondrosarcoma metastasis after ugonin V treatmen.

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