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miR-1301/TRIAP1 Axis Participates in Epirubicin-Mediated Anti-Proliferation and Pro-Apoptosis in Osteosarcoma
Lijun Yu1, Min Meng1, Yun Bao1
1Department of Pharmacy, Gansu Provincial Hospital, Lanzhou, Gansu, China.
Purpose:
Epirubicin is one of the most effective drugs against osteosarcoma. miR-1301 is involved in the occurrence and development of osteosarcoma. Whether miR-1301 is responsible for the chemosensitivity of osteosarcoma cells to epirubicin remains largely unknown.
Materials And Methods:
U2OS and SAOS-2 cells were treated with various concentrations of epirubicin. Flow cytometry was employed to evaluate cell apoptotic rate. Cell proliferation was measured by Cell Counting Kit-8 assay. Western blot and quantitative real-time polymerase chain reaction were utilized to detect the expressions of B-cell lymphoma-2 (Bcl-2), Bcl-2 assaciated X protein (Bax), cleaved-caspase-3, cleaved-poly (ADP-ribose) polymerases (PARP1), TP53-regulated inhibitor of apoptosis 1 (TRIAP1), and microRNA-1301 (miR-1301). The relationship between miR-1301 and TRIAP1 was determined by luciferase reporter assay.
Results:
Epirubicin inhibited proliferation in a dose-dependent manner, induced apoptosis, decreased the expression of Bcl-2, and increased the expressions of Bax, cleaved-caspase-3, and cleaved-PARP1 in osteosarcoma cells. miR-1301 was downregulated in U2OS and SAOS-2 cells. Importantly, epirubicin significantly increased the levels of miR-1301. Overexpression of miR-1301 suppressed proliferation and promoted apoptosis. Interestingly, those effects were enhanced by epirubicin. In contrast, miR-1301 depletion attenuated the epirubicin-mediated anti-osteosarcoma effect. miR-1301 negatively regulated the expression of TRIAP1 in U2OS and SAOS-2 cells. Furthermore, epirubicin inhibited the mRNA and protein levels of TRIAP1 by upregulating miR-1301 levels. Epirubicin suppressed cell proliferation by downregulating TRIAP1.
Conclusion:
miR-1301 was implicated in the chemosensitivity of osteosarcoma to epirubicin by modulating TRIAP1.
Insights
MicroRNA-1301 (miR-1301) enhances osteosarcoma cell sensitivity to epirubicin by downregulating TRIAP1. This finding provides a novel therapeutic target for improving epirubicin efficacy in osteosarcoma treatment.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Osteosarcoma is a primary bone malignancy with limited treatment options.
- Epirubicin is a key chemotherapeutic agent, but resistance remains a challenge.
- MicroRNA-1301 (miR-1301) is implicated in osteosarcoma development, but its role in drug sensitivity is unclear.
Purpose of the Study:
- To investigate the role of miR-1301 in osteosarcoma chemosensitivity to epirubicin.
- To elucidate the molecular mechanism underlying miR-1301's effect on epirubicin treatment.
Main Methods:
- Osteosarcoma cell lines (U2OS, SAOS-2) were treated with epirubicin.
- Cell proliferation and apoptosis were assessed using CCK-8 assay and flow cytometry.
- Expression levels of apoptosis markers (Bcl-2, Bax, cleaved-caspase-3, cleaved-PARP1) and miR-1301 were analyzed by qRT-PCR and Western blot.
- The regulatory relationship between miR-1301 and TRIAP1 was confirmed via luciferase reporter assay.
Main Results:
- Epirubicin inhibited cell proliferation and induced apoptosis in a dose-dependent manner.
- miR-1301 expression was downregulated in osteosarcoma cells and significantly upregulated by epirubicin.
- Overexpression of miR-1301 enhanced epirubicin's anti-cancer effects, while depletion attenuated them.
- miR-1301 directly targeted and downregulated TRIAP1 expression, mediating epirubicin's inhibitory effects on proliferation.
Conclusions:
- miR-1301 plays a crucial role in mediating osteosarcoma cell sensitivity to epirubicin.
- The miR-1301/TRIAP1 axis is a key pathway involved in epirubicin's efficacy.
- Targeting miR-1301 or TRIAP1 may represent a promising strategy to overcome epirubicin resistance in osteosarcoma.
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