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Intratibial Osteosarcoma Cell Injection to Generate Orthotopic Osteosarcoma and Lung Metastasis Mouse Models
Published on: October 28, 2021
miR-365 functions as a tumor suppressor by directly targeting CYR61 in osteosarcoma
Yawei Xu1, Haijiao Chu1, Yan Zhou1
1College of Bioengineering, Jilin Agricultural Science and Technology University, Jilin City 132101, PR China.
Abstract:
Increasing evidence indicates that microRNAs(miRNAs) are often aberrantly expressed in osteosarcoma (OS) and play critical roles in OS tumorigenesis. Therefore, the discovery of miRNAs may provide a new and powerful tool for understanding the mechanismof OS initiation and development. The aim of this study was to investigate the functional significance of miR-365 and identify its possible mechanism in OS cells. Here, wefound that the expression level of miR-365 is significantly downregulated in OS tissues and cell lines, and its expression isassociated with the clinical stage, distant metastasis, tumor grade, and poor overall survival rate. The overexpression of miR-365 is able to inhibit cell proliferation, migration, and invasion in Saos-2 and MG-63 cells. Moreover, the cysteine-rich angiogenic inducer 61 (CYR61) has been identified as a target of miR-365 in OS cells, and its expression is found to be significantly increased in OS tissues, which is negatively correlated with miR-365. Furthermore, CYR61 overexpression significantly attenuated the suppressive effects of miR-365 on the proliferation, migration, and invasion of Saos-2 and MG-63 cells. Therefore, we consider that miR-365 acts as a tumor suppressor in OS, partly, by targeting CYR61 expression.
Insights
MicroRNAs (miRNAs) like miR-365 are downregulated in osteosarcoma (OS), inhibiting tumor growth. Targeting CYR61, miR-365 acts as a tumor suppressor in OS by reducing proliferation and metastasis.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- MicroRNAs (miRNAs) are crucial regulators of gene expression implicated in various cancers.
- Aberrant miRNA expression is frequently observed in osteosarcoma (OS), suggesting their role in tumorigenesis.
Purpose of the Study:
- To investigate the functional role of miR-365 in osteosarcoma (OS).
- To elucidate the underlying molecular mechanism of miR-365 action in OS cells.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) to assess miR-365 expression in OS tissues and cell lines.
- Cell proliferation, migration, and invasion assays in OS cells with miR-365 overexpression.
- Western blotting and luciferase reporter assays to identify and validate miR-365 targets.
Main Results:
- miR-365 expression was significantly downregulated in OS tissues and cell lines, correlating with advanced clinical stage, metastasis, and poor survival.
- Overexpression of miR-365 suppressed proliferation, migration, and invasion in Saos-2 and MG-63 OS cells.
- Cysteine-rich angiogenic inducer 61 (CYR61) was identified as a direct target of miR-365, with its expression inversely correlated with miR-365 levels in OS. CYR61 overexpression counteracted miR-365's tumor-suppressive effects.
Conclusions:
- miR-365 functions as a tumor suppressor in osteosarcoma.
- miR-365 exerts its tumor-suppressive functions, at least partly, by targeting and downregulating CYR61 expression in OS cells.
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