MicroRNA-377-3p inhibits osteosarcoma progression by targeting CUL1 and regulating Wnt/β-catenin signaling pathway.

Abstract

Emerging studies highlight the crucial effects of microRNAs on cancer initiation and malignant progression of various tumors. This study focused on the biological effect of miR-377-3p on CUL1 and epithelial-mesenchymal transition (EMT) and Wnt/β-catenin pathways in osteosarcoma (OS). We performed quantitative real-time polymerase chain reaction (qRT-PCR) to analyze miR-377-3p and CUL1expression levels in OS tissues and MG-63 cells. Then, cell counting kit (CCK)-8 and Transwell assay were used to examine the functions of miR-377-3p in OS cell growth and metastasis abilities. Meanwhile, luciferase reporter assaywas used to validate CUL1as direct target of miR-377-3p. qRT-PCR and Western blot were then carried out to detect the impact of miR-377-3p on EMT and Wnt/β-catenin pathways.Tumor xenograft models were established to further examine the effects of miR-377-3p on OS tumorigenesisin vivo. miR-377-3p downregulation was frequently identified in OS tissues and cells, which was associated with worse prognosis of OS patients. Functional experiments showed miR-377-3p restoration could dramatically repress OS cell growth and migration by regulationof EMT and Wnt/β-catenin pathways. Moreover, luciferase reporter assayrevealed that CUL1acted as a functional target of miR-377-3p. Additionally, the elevatedCUL1expressions in OS tissues also indicated poor prognosis of OS patients. Furthermore, the OS tumor growth was also obviously inhibited by miR-377-3p overexpressionin vivo. Collectively, all the above findings revealed that miR-377-3p exerted anti-OS functions via CUL1and EMT and Wnt/β-catenin pathways. These resultsmay contribute to the development ofclinical OStreatment.