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Updated: Jul 5, 2025
Three-Dimensional Bone Extracellular Matrix Model for Osteosarcoma
Published on: April 12, 2019
MiR-383 sensitizes osteosarcoma cells to bortezomib treatment via down-regulating PSMB5
Haifan Wang1, Chuanyi Bai1, Xiaoqian Dang1
1Department of Orthopaedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, Shaanxi, China.
Background:
Proteasome inhibition is a promising strategy for cancer therapy. Bortezomib, which primarily targets the chymotrypsin-like activity of PSMB5, has demonstrated efficacy in various tumors. However, there is variable sensitivity to bortezomib, which could be attributed, in part, to variations in the expression of proteasome subunits.
Methods And Results:
In this study, we investigated whether miR-383 affects the expression of proteasome subunits in osteosarcoma (OS) cells, and if so, whether OS cells display differential sensitivity to bortezomib concerning miR-383 expression. We detected a decreased miR-383 expression in OS cells and tissues. Then we found a negative correlation between the cytotoxicity of bortezomib and the expression level of the proteasome 20S core particle subunit β5 (PSMB5). Intriguingly, we identified PSMB5 as a direct target of miR-383. Increased expression of miR-383 resulted in decreased PSMB5 expression and increased sensitivity to bortezomib in OS cells.
Conclusions:
In summary, our findings present the initial comprehensive analysis of the function of miR-383 in OS. The outcomes indicate that miR-383 may augment the anticancer effect of bortezomib through PSMB5 repression, offering a novel therapeutic approach in OS and a fresh pathway for proteasome regulation.
Insights
MicroRNA-383 (miR-383) may enhance bortezomib cancer therapy by reducing proteasome subunit PSMB5 expression in osteosarcoma. This suggests a new therapeutic strategy for proteasome regulation.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Proteasome inhibition is a key cancer therapy strategy.
- Bortezomib targets proteasome subunit PSMB5, showing efficacy in various cancers.
- Variable sensitivity to bortezomib may stem from proteasome subunit expression differences.
Purpose of the Study:
- To investigate miR-383's role in osteosarcoma (OS) proteasome subunit expression.
- To determine if miR-383 influences OS cell sensitivity to bortezomib.
Main Methods:
- Quantified miR-383 expression in OS cells and tissues.
- Assessed the correlation between bortezomib cytotoxicity and PSMB5 expression.
- Identified PSMB5 as a direct target of miR-383.
Main Results:
- Decreased miR-383 expression was observed in OS.
- A negative correlation was found between bortezomib efficacy and PSMB5 levels.
- Upregulating miR-383 decreased PSMB5 expression and enhanced bortezomib sensitivity in OS cells.
Conclusions:
- This study provides the first comprehensive analysis of miR-383 function in OS.
- miR-383 may enhance bortezomib's anticancer effects by repressing PSMB5.
- This offers a novel therapeutic approach for OS and a new pathway for proteasome regulation.
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