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Published on: April 7, 2017
MicroRNA-138 functions as a tumor suppressor in osteosarcoma by targeting differentiated embryonic chondrocyte gene 2
Baoen Jiang1, Weidong Mu2, Jiangquan Wang3
1Department of Traumatic Orthopaedics, The People 's Hospital of Dongying City of Shandong Province, No 317 Nanyi Road, Dongying, 257091, Shandong, China. baoen_jiang@163.com.
Background:
MicroRNA-138 (miR-138) has been proven to be a tumor suppressor gene in various types of tumors. However, the expression and the role of miR-138 in human osteosarcoma are still poorly understood. We investigated the function and the underlying mechanism of miR-138 in osteosarcoma.
Methods:
The expression of miR-138 in human osteosarcoma tissues and cell lines was detected by real-time PCR analysis. The gain-of-function and loss-of-function experiments were performed on osteosarcoma cell lines to investigate the effects of miR-138 on osteosarcoma progression, and to determine whether differentiated embryonic chondrocyte gene 2 (DEC2) mediates these effects. Cell proliferation, apoptosis and invasion were assessed by MTT, flow cytometry and transwell-matrigel assays. Dual-luciferase reporter assay was used to identify whether DEC2 is a direct target of miR-138.
Results:
MiR-138 was significantly downregulated in human osteosarcoma tissues and cell lines. Moreover, miR-138 expression was significantly lower in metastatic osteosarcoma tissues than that in non-metastatic tissues. The in vitro gain-of-function and loss-of-function experiments demonstrated that miR-138 inhibited cell proliferation and invasion, and promoted cell apoptosis of human osteosarcoma cells. DEC2 was verified as a direct target of miR-138, and DEC2 could reverse the inhibitory effect of miR-138 on osteosarcoma progression.
Conclusions:
These findings suggested that miR-138 acts as a tumor suppressor in osteosarcoma.miR-138 inhibited cell proliferation and invasion, as well as promoted cell apoptosis of human osteosarcoma cells, at least partially, by inhibiting the expression of DEC2. MiR-138/DEC2 may be a novel therapeutic target in osteosarcoma.
Insights
MicroRNA-138 (miR-138) is downregulated in osteosarcoma, acting as a tumor suppressor. It inhibits cancer progression by targeting DEC2, suggesting a new therapeutic strategy for osteosarcoma.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- MicroRNA-138 (miR-138) is recognized as a tumor suppressor in various cancers.
- The specific role and expression of miR-138 in human osteosarcoma remain largely uncharacterized.
- This study aimed to elucidate the function and regulatory mechanisms of miR-138 in osteosarcoma.
Purpose of the Study:
- To investigate the expression levels of miR-138 in human osteosarcoma tissues and cell lines.
- To determine the functional role of miR-138 in osteosarcoma cell progression, including proliferation, apoptosis, and invasion.
- To identify the molecular mechanism underlying miR-138's function, specifically its interaction with differentiated embryonic chondrocyte gene 2 (DEC2).
Main Methods:
- Real-time PCR was used to quantify miR-138 expression in osteosarcoma samples and cell lines.
- Gain-of-function and loss-of-function experiments were conducted to assess miR-138's impact on cell behavior.
- Cell proliferation, apoptosis, and invasion assays (MTT, flow cytometry, transwell-matrigel) were employed.
- Dual-luciferase reporter assays confirmed DEC2 as a direct target of miR-138.
Main Results:
- MiR-138 expression was significantly reduced in osteosarcoma tissues and cell lines compared to normal controls.
- Lower miR-138 levels correlated with metastatic status in osteosarcoma.
- Overexpression of miR-138 suppressed proliferation and invasion while promoting apoptosis in osteosarcoma cells.
- DEC2 was identified as a direct target, and its inhibition by miR-138 was crucial for the observed anti-tumor effects.
Conclusions:
- MiR-138 functions as a tumor suppressor in human osteosarcoma.
- MiR-138 inhibits osteosarcoma cell proliferation and invasion and promotes apoptosis, partly through the downregulation of DEC2.
- The miR-138/DEC2 axis represents a potential novel therapeutic target for osteosarcoma treatment.
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