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Updated: Aug 31, 2025
Three-Dimensional Bone Extracellular Matrix Model for Osteosarcoma
Published on: April 12, 2019
MicroRNA-455-3p inhibits osteosarcoma progression via HSF1 downregulation
Chao Wang1, Dagang Zhang1, Leidi Wang1
1Department of Bone and Joint Surgery, Guang'an People's Hospital, Guang'an, Sichuan 638000, PR China.
Objective:
This study was conducted to dissect the role and potential mechanism of microRNA (miR)-455-3p on osteosarcoma (OS) development.
Methods:
miR-455-3p and HSF1 expression in OS tissues were detected by RT-qPCR and western blot. Later, gain- and loss-of-function assays were implemented in OS cells U-2OS and MNNG. The expression of apoptosis-related genes was measured by RT-qPCR and western blot. MTT, Transwell, scratch test, and flow cytometry were utilized to test OS cell viability, invasion, migration, and apoptosis. The targeting relationship between miR-455-3p and HSF1 was assessed with a dual-luciferase reporter gene assay. The transplantation tumor experiment in nude mice was utilized for in vivo confirmation.
Results:
Downregulated miR-455-3p and upregulated HSF1 were displayed in OS tissues and cells. Mechanistically, miR-455-3p negatively targeted HSF1. MiR-455-3p inhibition or HSF1 overexpression increased MNNG and U-2OS cell proliferative, invasive, and migrating capabilities, while diminishing U-2OS cell apoptosis. Moreover, HSF1 overexpression negated the impacts of miR-455-3p upregulation on OS cell proliferative, invasive, migrating, and apoptotic abilities. Likewise, overexpressing miR-455-3p curtailed the growth of transplanted OS tumors through HSF1 repression.
Conclusion:
MiR-455-3p inhibits the development of OS cells by downregulating HSF1, highlighting the possibility of miR-455-3p as an innovative indicator of prognosis and a therapeutic target for OS.
Insights
MicroRNA (miR)-455-3p inhibits osteosarcoma (OS) development by targeting HSF1. This finding suggests miR-455-3p could be a novel therapeutic target and prognostic indicator for OS patients.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Osteosarcoma (OS) is a primary bone malignancy with significant mortality.
- MicroRNAs (miRNAs) play crucial roles in cancer development and progression.
- The specific role of miR-455-3p in OS remains largely unexplored.
Purpose of the Study:
- To investigate the function of miR-455-3p in osteosarcoma (OS) development.
- To elucidate the underlying molecular mechanism of miR-455-3p action in OS.
- To assess the potential of miR-455-3p as a therapeutic target for OS.
Main Methods:
- Quantitative real-time PCR (RT-qPCR) and Western blot were used to measure miR-455-3p and HSF1 expression in OS tissues and cells.
- Gain- and loss-of-function assays were performed in OS cell lines (U-2OS, MNNG).
- Cell viability, invasion, migration, and apoptosis were assessed using MTT, Transwell, scratch assays, and flow cytometry. In vivo tumor growth was evaluated in nude mice.
Main Results:
- miR-455-3p was downregulated, while HSF1 was upregulated in OS tissues and cells.
- miR-455-3p directly targeted and downregulated HSF1 expression.
- Upregulation of miR-455-3p inhibited OS cell proliferation, invasion, and migration, and promoted apoptosis, effects mediated by HSF1 downregulation.
Conclusions:
- miR-455-3p functions as a tumor suppressor in osteosarcoma by inhibiting HSF1.
- miR-455-3p demonstrates potential as a prognostic biomarker and a novel therapeutic target for osteosarcoma.
