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Piperlongumine inhibits the progression of osteosarcoma by downregulating the SOCS3/JAK2/STAT3 pathway via miR-30d-5p

Yawei Hu1, Xinle Luo1, Jianhua Zhou1

  • 1Department of Spine Surgery, People's Hospital of Longhua, Affiliated Hospital of Southern Medical University, Guangdong 518000, Shenzhen, China.

Life Sciences
|April 16, 2021
PubMed
Abstract

Insights

Piperlongumine (PL) effectively inhibits osteosarcoma progression by suppressing cell growth, migration, and metastasis. It achieves this by downregulating miR-30d-5p, which in turn inhibits the SOCS3-mediated JAK2/STAT3 pathway.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Osteosarcoma (OS) is a primary bone malignancy with significant metastatic potential.
  • Understanding the molecular mechanisms underlying OS progression is crucial for developing effective therapies.

Purpose of the Study:

  • To investigate the anti-cancer effects of Piperlongumine (PL) on osteosarcoma cells.
  • To elucidate the molecular pathways targeted by PL in osteosarcoma.

Main Methods:

  • Cytotoxicity and apoptosis were assessed using MTT assays and Annexin V/propidium iodide staining.
  • Cell migration, invasion, and epithelial-mesenchymal transition (EMT) were evaluated via Transwell assays and Western blotting.
  • The role of Suppressor of Cytokine Signaling 3 (SOCS3) and microRNA-30d-5p (miR-30d-5p) was analyzed using RT-qPCR, dual-luciferase reporter assays, and in vivo xenograft models.

Main Results:

  • Piperlongumine significantly inhibited OS cell growth, migration, invasion, and EMT, while promoting apoptosis.
  • PL treatment led to increased SOCS3 protein levels and inactivation of the JAK2/STAT3 pathway.
  • SOCS3 was identified as a direct target of miR-30d-5p, and its downregulation by miR-30d-5p was shown to counteract the anti-tumor effects of PL.

Conclusions:

  • Piperlongumine exerts anti-osteosarcoma effects by inhibiting miR-30d-5p, leading to the downregulation of SOCS3 and subsequent inactivation of the JAK2/STAT3 pathway.
  • These findings highlight a novel therapeutic strategy targeting the miR-30d-5p/SOCS3/JAK2/STAT3 axis in osteosarcoma treatment.
Keywords:
JAK2/STAT3OsteosarcomaPiperlongumineSuppressor of cytokine signaling 3microRNA-30d-5p

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