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miR-140 inhibits osteosarcoma progression by impairing USP22-mediated LSD1 stabilization and promoting p21 expression

Wei Liu1, Dunwei Wang2, Lidi Liu1

  • 1Department of Spine Surgery, The First Hospital of Jilin University, Changchun 130021, P.R. China.

Molecular Therapy. Nucleic Acids
|April 19, 2021
PubMed

Insights

MicroRNA-140 acts as a tumor suppressor in osteosarcoma, inhibiting cancer growth and spread. Targeting this microRNA may offer new therapeutic strategies for this bone cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Osteosarcoma is a prevalent bone cancer in young individuals.
  • Metastasis and chemoresistance remain significant challenges in osteosarcoma treatment.
  • Understanding molecular pathogenesis is crucial for developing novel therapies.

Purpose of the Study:

  • To investigate the molecular mechanisms underlying osteosarcoma development.
  • To identify key molecular players in osteosarcoma progression.
  • To explore the therapeutic potential of microRNA-140 (miR-140) in osteosarcoma.

Main Methods:

  • Comparative analysis of 65 osteosarcoma tissues and adjacent normal tissues.
  • Comparison of osteosarcoma cell lines with normal osteoblast cell lines.
  • Investigation of the miR-140/ubiquitin-specific protease 22 (USP22)/lysine-specific demethylase 1 (LSD1)/p21 axis.
  • Functional assays including cell proliferation, migration, invasion, apoptosis, and in vivo tumorigenesis studies.

Main Results:

  • Osteosarcoma tissues and cells showed decreased miR-140 and p21 expression, with increased USP22 and LSD1.
  • miR-140 overexpression suppressed osteosarcoma cell proliferation, migration, and invasion, while promoting apoptosis by targeting USP22.
  • USP22 overexpression counteracted the effects of miR-140.
  • miR-140 overexpression or USP22 knockdown induced ubiquitination and degradation of LSD1.
  • In vivo studies confirmed miR-140's tumor-suppressive role.

Conclusions:

  • The miR-140/USP22/LSD1/p21 axis is implicated in osteosarcoma pathogenesis.
  • miR-140 functions as a tumor suppressor in osteosarcoma.
  • miR-140 represents a promising therapeutic target for osteosarcoma treatment.
Keywords:
lysine-specific demethylase-1microRNA-140osteosarcomap21ubiquitin-specific protease 22ubiquitination

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