Title:miR-141-3p Promotes the Cisplatin Sensitivity of Osteosarcoma
Cell through Targeting the Glutaminase [GLS]-Mediated Glutamine
Metabolism
Volume: 23
Issue: 2
Author(s): Xueli Zhou, Panpan Wei , Xinju Wang, Jianguo Zhang and Yulin Shi *
Affiliation:
- Department of Spinal Surgery, Weifang People's Hospital.
Weifang City, Shandong Province, 261041, P.R. China
Keywords:
Osteosarcoma, cisplatin resistance, miR-141-3p, glutaminase, glutamine, metabolism.
Abstract:
Aims: This study aimed to evaluate the roles and molecular targets of
miRNA-141-3p in the cisplatin sensitivity of osteosarcoma.
Background: Osteosarcoma is one of the most common-type bone tumors, occurring
mainly in children and adolescents. Cancer cells display dysregulated cellular
metabolism, such as the abnormally elevated glutamine metabolism.
Objective: Non-coding RNA miRNA-141-3p has been reported to act as a tumor
suppressor in osteosarcoma. Currently, the precise molecular mechanisms for the miR-
141-3p-mediated chemosensitivity through regulating glutamine metabolism remain
unclear.
Methods: We collected thirty paired OS tumors and their adjacent normal tissues. The
osteosarcoma cell lines [Saos-2] and normal osteoblast cells, hFOB1.19, were used for
in vitro experiments. RT-qPCR and Western blot were applied for gene expression
detections. Targets of miR-141-3p were predicted from starBase. The MTT and flow
cytometric assays were performed to determine cell growth and apoptosis rates. The
cellular glutamine metabolism was monitored by glutamine uptake assay and the
glutaminase [GLS] activity assay.
Results: We reported that miR-141-3p were significantly downregulated in
osteosarcoma tissues and cells. Overexpression of miR-141-3p suppressed OS cell
growth and sensitized OS cells to cisplatin. In addition, glutamine metabolism was
significantly increased in osteosarcoma. We characterized that GLS played oncogenic
roles in osteosarcoma and validated GLS was a direct target of miR-141-3p in OS cells.
Rescue experiments consistently demonstrated that miR-141-3p-promoted cisplatin
sensitivity was achieved by targeting GLS directly.
Conclusion: Overall, our findings revealed new molecular mechanisms of the miR-141-
3p-modulated cisplatin sensitization through targeting the GLS-glutamine metabolism
pathway. This study will contribute to developing new therapeutic approaches for the
treatments of chemoresistant osteosarcoma.
