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Published on: October 28, 2021
miR-429 inhibits osteosarcoma progression by targeting HOXA9 through suppressing Wnt/β-catenin signaling pathway
Liangzhi Sun1, Libo Wang2, Suxian Luan3
1Department of Orthopedics, Weifang People's Hospital, Weifang, Shandong 261041, P.R. China.
Abstract:
Osteosarcoma (OS) is the most commonly diagnosed malignant cancer of bone that occurs in adolescents and children. Mounting number of studies have indicated that miRNAs are increasingly playing fundamental roles in OS development. Thus, the biological function of miR-429 in OS progression was explored. The results of RT-qPCR revealed that miR-429 was downregulated in OS tissues and OS cell lines (MG-63, U2OS, Saos-2) while homeobox A9 (HOXA9) was markedly increased. Moreover, HOXA9 was confirmed as a direct target of miR-429 by using luciferase reporter assay. It was identified that miR-429 exhibited a suppressive effect on OS progression while HOXA9 showed the oncogenic function in OS progression by using MTT and Transwell assays. More importantly, rescue assays manifested that HOXA9 can partially overturn the suppressive effect of miR-429 on OS. Overexpression of miR-429 inhibited the activation of Wnt/β-catenin signaling pathway. In conclusion, miR-429 suppressed OS progression by targeting HOXA9 through Wnt/β-catenin pathway.
Insights
MicroRNA-429 (miR-429) suppresses osteosarcoma progression by targeting HOXA9. This microRNA inhibits cancer growth through the Wnt/β-catenin pathway, offering potential therapeutic insights.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Osteosarcoma (OS) is a primary bone cancer predominantly affecting children and adolescents.
- MicroRNAs (miRNAs) are increasingly recognized for their critical roles in OS pathogenesis and progression.
Purpose of the Study:
- To investigate the functional role of miR-429 in osteosarcoma progression.
- To elucidate the molecular mechanisms underlying miR-429's action in OS.
Main Methods:
- Quantitative real-time PCR (RT-qPCR) to assess miR-429 and HOXA9 expression.
- Luciferase reporter assay to confirm the direct targeting of HOXA9 by miR-429.
- MTT and Transwell assays to evaluate cell proliferation and invasion.
- Rescue assays to validate the functional relationship between miR-429 and HOXA9.
- Western blot analysis to examine Wnt/β-catenin signaling pathway activation.
Main Results:
- miR-429 was significantly downregulated in OS tissues and cell lines, while HOXA9 expression was upregulated.
- HOXA9 was identified as a direct target of miR-429.
- miR-429 suppressed OS cell proliferation and invasion, whereas HOXA9 promoted these processes.
- Overexpression of HOXA9 partially reversed the inhibitory effects of miR-429.
- miR-429 overexpression inhibited the activation of the Wnt/β-catenin signaling pathway.
Conclusions:
- miR-429 acts as a tumor suppressor in osteosarcoma.
- miR-429 inhibits OS progression by directly targeting HOXA9 and downregulating the Wnt/β-catenin pathway.
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