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Anticancer effects of melatonin via regulating lncRNA JPX-Wnt/β-catenin signalling pathway in human osteosarcoma

Yuan Li1,2, Jilong Zou3, Bo Li4

  • 1Department of Pharmacology, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.

Journal of Cellular and Molecular Medicine
|September 21, 2021
PubMed

Insights

Melatonin effectively inhibits osteosarcoma (OS) cell growth, migration, and invasion. This natural agent works by downregulating lncRNA JPX expression, impacting the Wnt/β-catenin pathway, offering a potential new treatment for this aggressive bone cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Osteosarcoma (OS) is an aggressive bone cancer primarily affecting children and adolescents, necessitating novel therapeutic strategies.
  • Current treatments for OS are limited, highlighting the urgent need for effective drug development.

Purpose of the Study:

  • To investigate the therapeutic potential and underlying mechanisms of melatonin in osteosarcoma (OS) cells.
  • To determine melatonin's effects on OS cell viability, proliferation, migration, invasion, and metastasis.
  • To elucidate the role of long non-coding RNA JPX (lncRNA JPX) and the Wnt/β-catenin pathway in melatonin's action on OS.

Main Methods:

  • Cell viability, proliferation, migration, and invasion assays (trypan blue, MTT, colony formation, wound healing, Transwell).
  • Quantitative real-time PCR (qPCR) to assess lncRNA JPX expression.
  • Western blot analysis for protein expression.
  • Gain and loss of function assays for lncRNA JPX.
  • Investigation of the Wnt/β-catenin signaling pathway.

Main Results:

  • Melatonin significantly inhibited OS cell viability, proliferation, migration, invasion, and metastasis in a dose-dependent manner.
  • Melatonin treatment downregulated the expression of lncRNA JPX in OS cell lines (Saos-2, MG63, U2OS).
  • Overexpression of lncRNA JPX increased OS cell viability, proliferation, and metastasis, while melatonin suppressed these effects by inhibiting lncRNA JPX via the Wnt/β-catenin pathway.

Conclusions:

  • Melatonin exhibits potent anti-cancer effects against osteosarcoma cells by suppressing lncRNA JPX expression and modulating the Wnt/β-catenin signaling pathway.
  • Melatonin represents a promising natural agent for the potential treatment of osteosarcoma.
  • Targeting lncRNA JPX and the Wnt/β-catenin pathway offers a viable therapeutic strategy for OS.
Keywords:
LncRNAsWnt/β-catenin pathwaymelatoninosteosarcomatherapeutic methods

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