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Knockdown of microRNA-203 reduces cisplatin chemo-sensitivity to osteosarcoma cell lines MG63 and U2OS in vitro by
Zhengxiang Huang1, Lintuo Huang1, Lue Liu2
1Department of Orthopedics, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Abstract:
Clinical studies have reported that miRNAs abnormal expression are associated with the generation of cisplatin-resistant to osteosarcoma. Our previous research found that miR-203 is downregulated in osteosarcoma cells and overexpressed miR-203 exerts antitumor properties on osteosarcoma cells. However, the role and mechanism of miR-203 in regulating the sensitivity of cisplatin in osteosarcoma cells remains unclear. This study aimed to investigate the effects of miR-203 in cisplatin therapy for osteosarcoma cells in vitro and determined the underlying mechanism. In this study, we found that miR-203 was significantly upregulated in osteosarcoma cells after exposure to cisplatin. miR-203 knockdown reduced the sensitivity of osteosarcoma cells to cisplatin by suppressing cell apoptosis, cell cycle arrest, and inducing invasion. Meanwhile, we found that miR-203 knockdown reduces the therapeutic sensitivity of osteosarcoma cells by upregulating RUNX2. Moreover, we found that RUNX2 silencing sensitizes osteosarcoma cells to chemotherapy treatment of cisplatin. In summary, our findings demonstrated that miR-203 knockdown reduces cisplatin chemo-sensitivity to osteosarcoma cells in vitro by targeting RUNX2, and speculated that miR-203 may be a target for drug resistance of osteosarcoma to cisplatin.
Insights
MicroRNA-203 (miR-203) downregulation reduces osteosarcoma cells
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Abnormal microRNA (miRNA) expression is linked to cisplatin resistance in osteosarcoma.
- Our prior work showed miR-203 is downregulated in osteosarcoma and has antitumor effects.
- The precise role of miR-203 in modulating cisplatin sensitivity in osteosarcoma remains undetermined.
Purpose of the Study:
- To investigate the impact of miR-203 on cisplatin therapy efficacy in osteosarcoma cells.
- To elucidate the underlying molecular mechanisms by which miR-203 influences cisplatin resistance.
Main Methods:
- Osteosarcoma cells were treated with cisplatin.
- miR-203 expression levels were analyzed.
- miR-203 knockdown and RUNX2 silencing experiments were performed.
- Cell apoptosis, cell cycle, and invasion assays were conducted.
Main Results:
- miR-203 expression significantly increased in osteosarcoma cells following cisplatin exposure.
- Knockdown of miR-203 decreased cisplatin sensitivity by inhibiting apoptosis and cell cycle arrest while promoting invasion.
- miR-203 knockdown led to increased RUNX2 expression, reducing chemosensitivity.
- Silencing RUNX2 restored cisplatin sensitivity in osteosarcoma cells.
Conclusions:
- miR-203 downregulation reduces cisplatin chemo-sensitivity in osteosarcoma cells by targeting RUNX2.
- miR-203 may serve as a potential therapeutic target to overcome cisplatin resistance in osteosarcoma.
- These findings offer insights into the molecular mechanisms of drug resistance in osteosarcoma.
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