microRNA‑377‑3p inhibits osteosarcoma progression by targeting CUL1 and regulating Wnt/β‑catenin signaling pathway

• K. Liang ^[1] ; L. Liao ^[2] ; Q. Liu ^[1] ; Q. Ouyang ^[2] ; L. Jia ^[2] ; G. Wu ^[3]
  1. [1] Department of Laboratory, Nanxishan Hospital of Guangxi Zhuang Autonomous Region, Xiangshan District, Guilin 541002, Guangxi, China
  2. [2] Department of Laboratory, Affiliated Hospital of Guilin Medical University, Xiufeng District, Guilin 541001, Guangxi, China
  3. [3] Department of Oncology, Affiliated Hospital of Guilin Medical University, Xiufeng District, Guilin 541001, Guangxi, China

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• Localización: Clinical & translational oncology, ISSN 1699-048X, Vol. 23, Nº. 11, 2021, págs. 2350-2357
• Idioma: inglés
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  • 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