microRNA‑377‑3p inhibits osteosarcoma progression by targeting CUL1 and regulating Wnt/β‑catenin signaling pathway
2021
Objective 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).
Methods We performed quantitative real-time polymerase chain reaction (qRT-PCR) to analyze miR-377-3p and
CUL1 expression 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 assay was
used to validate CUL1 as 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 tumorigenesis in vivo.
Results miR-377-3p downregulation was frequently identified in OS tissues and cells, which was associated with worse prog-
nosis of OS patients. Functional experiments showed miR-377-3p restoration could dramatically repress OS cell growth and
migration by regulation of EMT and Wnt/β-catenin pathways. Moreover, luciferase reporter assay revealed that CUL1 acted
as a functional target of miR-377-3p. Additionally, the elevated CUL1 expressions in OS tissues also indicated poor progno-
sis of OS patients. Furthermore, the OS tumor growth was also obviously inhibited by miR-377-3p overexpression in vivo.
Conclusions Collectively, all the above findings revealed that miR-377-3p exerted anti-OS functions via CUL1 and EMT
and Wnt/β-catenin pathways. These results may contribute to the development of clinical OS treatment
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