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Published on: October 27, 2014
MicroRNA-22-3p targeted regulating transcription factor 7-like 2 (TCF7L2) constrains the Wnt/β-catenin pathway and
YuanLiang Xue1, Ya Guo2, Ning Liu3
1Department of Orthopedics, Clinical Medical College of Shandong Uiniversity of Traditional Chinese Medicine, JiNan City, ShanDong Province, China.
Abstract:
Various studies have manifested that microRNAs (miRNAs) are involved in the modulation of the occurrence and development of osteosarcoma (OS). However, whether miR-22-3p is associated with OS growth remains unclear. In the study, the potential molecular mechanisms of miR-22-3p in OS was explored. It was affirmed that miR-22-3p was associated with distant metastasis and tumor size in OS patients, and reduced in OS tissues and cells while transcription factor 7-like 2 (TCF7L2) was elevated. Elevated miR-22-3p repressed OS cell progression, and the Wnt/β-catenin pathway, while elevated TCF7L2 was opposite. MiR-22-3p targeted TCF7L2 in OS. In functional rescue experiments, knockdown of miR-22-3p on OS progression and promotion of Wnt/β-catenin were reversed by simultaneous knockdown of TCF7L2. Transplantation experiments in nude mice showed that elevated miR-22-3p repressed OS tumor growth and decreased TCF7L2, Wnt and β-catenin. Shortly, this study suggest that miR-22-3p refrains the Wnt/β-catenin pathway by targeting TCF7L2 and thereby preventing OS deterioration. MiR-22-3p/TCF7L2 axis is supposed to be a candidate molecular target for future OS treatment.
Insights
MicroRNA-22-3p (miR-22-3p) inhibits osteosarcoma (OS) progression by targeting TCF7L2 and suppressing the Wnt/β-catenin pathway. This miR-22-3p/TCF7L2 axis offers a potential therapeutic target for osteosarcoma treatment.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- MicroRNAs (miRNAs) play a role in osteosarcoma (OS) development.
- The specific role of miR-22-3p in OS progression was previously unclear.
Purpose of the Study:
- To investigate the molecular mechanisms of miR-22-3p in osteosarcoma.
- To explore the potential of the miR-22-3p/TCF7L2 axis as a therapeutic target.
Main Methods:
- Analysis of miR-22-3p and TCF7L2 expression in OS tissues and cells.
- In vitro experiments assessing the effects of miR-22-3p and TCF7L2 on OS cell progression and the Wnt/β-catenin pathway.
- Functional rescue experiments and in vivo transplantation studies in nude mice.
Main Results:
- miR-22-3p was downregulated in OS tissues and cells, inversely correlated with TCF7L2.
- Elevated miR-22-3p suppressed OS cell proliferation, migration, and the Wnt/β-catenin pathway.
- TCF7L2 was identified as a direct target of miR-22-3p, and its knockdown reversed miR-22-3p's effects.
- In vivo studies confirmed that miR-22-3p inhibited OS tumor growth by downregulating TCF7L2 and the Wnt/β-catenin pathway.
Conclusions:
- miR-22-3p acts as a tumor suppressor in osteosarcoma by targeting TCF7L2 and inhibiting the Wnt/β-catenin pathway.
- The miR-22-3p/TCF7L2 axis represents a promising molecular target for osteosarcoma therapy.
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