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miR-766-3p Targeting BCL9L Suppressed Tumorigenesis, Epithelial-Mesenchymal Transition, and Metastasis Through the

Sheng Zhang1, Hongtao Chen1, Wanshun Liu1

  • 1Department of Orthopedics, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Frontiers in Cell and Developmental Biology
|October 29, 2020
PubMed

Insights

MicroRNA miR-766-3p suppresses osteosarcoma progression by inhibiting B-Cell Lymphoma 9-Like Protein (BCL9L) and impacting the β-catenin pathway. This finding highlights miR-766-3p as a potential therapeutic target for osteosarcoma.

Area of Science:

  • Molecular Biology
  • Oncology
  • Biochemistry

Background:

  • Aberrant microRNA (miRNA) expression is implicated in osteosarcoma (OS) carcinogenesis.
  • Understanding specific miRNA roles is crucial for developing targeted therapies.

Purpose of the Study:

  • To investigate the role of miR-766-3p in osteosarcoma (OS) development.
  • To explore the underlying molecular mechanisms of miR-766-3p in OS.

Main Methods:

  • Analysis of the GSE65071 dataset from the GEO database to identify differentially expressed miRNAs.
  • Expression analysis in OS tissues and cells.
  • In vitro and in vivo functional assays (proliferation, EMT, migration, invasion).
  • Luciferase reporter assay and Western blotting to validate B-Cell Lymphoma 9-Like Protein (BCL9L) as a target.
  • Rescue experiments and analysis of the β-Catenin/TCF-4 signaling pathway.

Main Results:

  • miR-766-3p was significantly downregulated in osteosarcoma tissues and cells.
  • Overexpression of miR-766-3p suppressed OS cell proliferation, epithelial-mesenchymal transition (EMT), migration, and invasion.
  • BCL9L was identified as a direct downstream target of miR-766-3p, with inverse correlation in expression.
  • BCL9L overexpression rescued the inhibitory effects of miR-766-3p.
  • The miR-766-3p/BCL9L axis regulates osteosarcoma progression via the β-catenin signaling pathway.

Conclusions:

  • miR-766-3p acts as a tumor suppressor in osteosarcoma by targeting BCL9L.
  • The miR-766-3p/BCL9L interaction influences OS metastasis through the β-catenin pathway.
  • miR-766-3p represents a potential therapeutic biomarker for osteosarcoma.
Keywords:
BCL9LEMTmetastasismiR-766-3posteosarcomaβ-catenin

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