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Updated: Jan 10, 2026
A Syngeneic Orthotopic Osteosarcoma Sprague Dawley Rat Model with Amputation to Control Metastasis Rate
Published on: May 3, 2021
Demethylase, ALKBH1, regulates osteosarcoma chemosensitivity through FZD8/Wnt/β-catenin signaling pathway in the m7G
Xiangyao Li1, Zili Lin2, Qing Liu1
1Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, PR China.
Background:
The escalating chemoresistance in osteosarcoma (OS) has impeded therapeutic advancements, underscoring the critical need to elucidate the mechanisms driving OS progression. Epigenetic alterations have been implicated in the pathogenesis and progression of various cancers, including OS, suggesting that targeting these modifications could advance cancer research and therapeutic strategies.
Methods:
The roles of ALKBH1, a demethylase, in OS were explored using bioinformatics and in-vitro and in-vivo experiments. Additionally, transcriptome sequencing and RIP sequencing were performed to explore the anti-OS mechanism of ALKBH1, and rescue assays, RIP-qPCR, and m7G-MeRIP-qPCR were conducted to validate the intricate relation between ALKBH1, FZD8, Wnt/β-catenin signaling pathway, and OS chemosensitivity.
Results:
The present study revealed that ALKBH1 served as a tumor suppressor by promoting apoptosis, inhibiting proliferation, and suppressing metastasis in OS. Notably, ALKBH1 overexpression significantly enhanced the chemosensitivity of OS to doxorubicin. Furthermore, we demonstrated that ALKBH1 regulated the FZD8/β-catenin signaling pathway through m7G methylation, thereby suppressing OS progression both in vitro and in vivo.
Conclusion:
This study identified ALKBH1 as a promising therapeutic target, particularly for overcoming OS chemoresistance. The ALKBH1/FZD8/β-catenin axis and its associated m7G methylation mechanisms may offer novel avenues for OS researches and treatments.
Insights
AlkBh1 acts as a tumor suppressor in osteosarcoma (OS) by inhibiting growth and metastasis. Overexpression of AlkBh1 enhances chemoresistance, offering a new therapeutic target for OS treatment.
Area of Science:
- Oncology
- Epigenetics
- Molecular Biology
Background:
- Osteosarcoma (OS) chemoresistance hinders treatment progress.
- Epigenetic modifications are key drivers in OS pathogenesis.
- Targeting epigenetic alterations presents therapeutic opportunities.
Purpose of the Study:
- To investigate the role of ALKBH1, a demethylase, in osteosarcoma (OS).
- To explore the anti-OS mechanisms of ALKBH1.
- To elucidate the relationship between ALKBH1, FZD8, Wnt/β-catenin signaling, and OS chemosensitivity.
Main Methods:
- Bioinformatics analysis, in-vitro and in-vivo experiments.
- Transcriptome and RIP sequencing.
- Rescue assays, RIP-qPCR, and m7G-MeRIP-qPCR.
Main Results:
- ALKBH1 functions as a tumor suppressor, inhibiting OS proliferation, metastasis, and promoting apoptosis.
- ALKBH1 overexpression significantly improves OS chemosensitivity to doxorubicin.
- ALKBH1 regulates the FZD8/β-catenin pathway via m7G methylation, suppressing OS progression.
Conclusions:
- ALKBH1 is a potential therapeutic target for overcoming osteosarcoma chemoresistance.
- The ALKBH1/FZD8/β-catenin axis and m7G methylation offer novel therapeutic strategies for OS.
