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Single-cell RNA and bulk sequencing analysis reveals that formononetin inhibits GTSF1 to exert anti-osteosarcoma
Tianyu Xie1, Jiming Liang2, Chengsen Lin3
1Department of Traumatic Orthopaedic, The First Affiliated Hospital of Guangxi Medical University, 530021 Nanning, China.
Abstract:
As the most common primary malignant bone tumor, osteosarcoma (OS) is characterized by drug resistance and poor prognosis, highlighting the urgent need for promising therapeutic agents. Formononetin (FMN), a natural product derived from Spatholobi Caulis, has been reported to possess anti-tumor properties. However, its role in OS has not yet been elucidated. In the present study, we established an OS patient-derived xenograft model to investigate the effects of FMN and the underlying mechanisms of its effects on OS. When FMN treatment was completed, bulk transcriptome sequencing was conducted, and the analyses were combined with OS single-cell RNA sequencing (scRNA-seq) data. Results indicated that GTSF1 was up-regulated in OS but down-regulated after FMN intervention, which may regulate the apoptosis of OS cells. Furthermore, the qRT-PCR and IHC results demonstrated that GTSF1 expression was significantly up-regulated in OS cells, whereas FMN expression was down-regulated both in vitro and in vivo. Moreover, in vitro experiments revealed that FMN effectively promoted apoptosis and suppressed the proliferation, migration, and invasion of OS cells. Therefore, this study demonstrated that FMN exerts anti-OS effects by down-regulating GTSF1 expression, thus effectively promoting the apoptosis and inhibiting the proliferation of OS cells, making FMN a promising anti-OS drug.
Insights
Formononetin (FMN) shows promise as an osteosarcoma (OS) treatment by inhibiting tumor growth and promoting cell death. This natural compound works by down-regulating GTSF1 expression, offering a new therapeutic avenue for this challenging bone cancer.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Osteosarcoma (OS) is the most common primary malignant bone tumor.
- OS is characterized by drug resistance and poor prognosis, necessitating novel therapeutic agents.
- Formononetin (FMN), a natural product, has demonstrated anti-tumor properties, but its role in OS was previously unknown.
Purpose of the Study:
- To investigate the anti-tumor effects of Formononetin (FMN) on osteosarcoma (OS).
- To elucidate the underlying mechanisms of FMN's action in OS.
- To evaluate FMN as a potential therapeutic agent for OS.
Main Methods:
- Established an OS patient-derived xenograft model.
- Performed bulk transcriptome sequencing and analyzed OS single-cell RNA sequencing (scRNA-seq) data.
- Utilized qRT-PCR and IHC for gene expression analysis; conducted in vitro experiments.
Main Results:
- GTSF1 was found to be up-regulated in OS and down-regulated following FMN intervention.
- FMN treatment effectively promoted apoptosis and suppressed proliferation, migration, and invasion of OS cells in vitro.
- GTSF1 expression was significantly up-regulated in OS cells, while FMN expression was down-regulated both in vitro and in vivo.
Conclusions:
- Formononetin (FMN) exerts anti-osteosarcoma (OS) effects by down-regulating GTSF1 expression.
- FMN effectively promotes OS cell apoptosis and inhibits proliferation, migration, and invasion.
- FMN represents a promising therapeutic drug candidate for osteosarcoma treatment.
