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

K Liang1, L Liao2, Q Liu1

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

Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico
|June 16, 2021
PubMed
Abstract

Insights

MicroRNA miR-377-3p is downregulated in osteosarcoma (OS) and inhibits tumor growth and metastasis. Restoring miR-377-3p suppresses cancer progression by targeting CUL1 and affecting EMT and Wnt/β-catenin pathways.

Area of Science:

  • Oncology
  • Molecular Biology
  • Gene Regulation

Background:

  • MicroRNAs (miRNAs) play critical roles in cancer initiation and progression.
  • Osteosarcoma (OS) is a primary bone malignancy with significant metastatic potential.
  • Understanding miRNA involvement in OS pathogenesis is crucial for developing targeted therapies.

Purpose of the Study:

  • To investigate the role of miR-377-3p in osteosarcoma (OS).
  • To elucidate the regulatory effects of miR-377-3p on CUL1, epithelial-mesenchymal transition (EMT), and Wnt/β-catenin signaling in OS.
  • To evaluate the therapeutic potential of miR-377-3p in OS treatment.

Main Methods:

  • Quantitative real-time polymerase chain reaction (qRT-PCR) for gene expression analysis.
  • Cell counting kit (CCK)-8 and Transwell assays for functional assessment of cell growth and metastasis.
  • Luciferase reporter assay to confirm CUL1 as a direct target of miR-377-3p.
  • Western blot to analyze pathway-related protein expression.
  • In vivo tumor xenograft models to assess tumorigenesis.

Main Results:

  • miR-377-3p was frequently downregulated in OS tissues and associated with poor prognosis.
  • Restoration of miR-377-3p significantly inhibited OS cell proliferation and migration.
  • CUL1 was identified as a direct target of miR-377-3p, and its elevated expression correlated with poor prognosis.
  • miR-377-3p suppressed EMT and modulated the Wnt/β-catenin pathway.
  • Overexpression of miR-377-3p inhibited OS tumor growth in vivo.

Conclusions:

  • miR-377-3p exhibits anti-tumor functions in osteosarcoma by targeting CUL1 and influencing EMT and Wnt/β-catenin pathways.
  • miR-377-3p represents a potential therapeutic target for osteosarcoma treatment.
  • These findings contribute to the development of novel clinical strategies for OS management.
Keywords:
CUL1Epithelial-to-mesenchymal transitionMiR-377-3pOsteosarcomaWnt/β-catenin

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