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

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Abstract

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 prognosis 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 prognosis 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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Author notes

  1. K. Liang and L. Liao contributed equally to this work.

Authors and Affiliations

  1. Department of Laboratory, Nanxishan Hospital of Guangxi Zhuang Autonomous Region, Xiangshan District, Guilin, 541002, Guangxi, China

    K. Liang & Q. Liu

  2. Department of Laboratory, Affiliated Hospital of Guilin Medical University, Xiufeng District, Guilin, 541001, Guangxi, China

    L. Liao, Q. Ouyang & L. Jia

  3. Department of Oncology, Affiliated Hospital of Guilin Medical University, Xiufeng District, Guilin, 541001, Guangxi, China

    G. Wu

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  1. K. Liang
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  4. Q. Ouyang
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Contributions

KL, LL and QL are responsible for the conception or design of the work. QO, LJ and GW contribute the acquisition, analysis, or interpretation of data for the work. All authors finally approved the manuscript version to be published.

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Correspondence to G. Wu.

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The study was approved by Ethical Committee of Nanxishan Hospital of Guangxi Zhuang Autonomous Region and conducted in accordance with the ethical standards.

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Liang, K., Liao, L., Liu, Q. et al. microRNA-377-3p inhibits osteosarcoma progression by targeting CUL1 and regulating Wnt/β-catenin signaling pathway. Clin Transl Oncol 23, 2350–2357 (2021). https://doi.org/10.1007/s12094-021-02633-6

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  • DOI: https://doi.org/10.1007/s12094-021-02633-6

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