MiR-100 up-regulation enhanced cell autophagy and apoptosis induced by cisplatin in osteosarcoma by targeting mTOR

Z. Yu, N. Li, K. Jiang, N. Zhang, L.-L. Yao

Department of Medical Oncology, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China. qycsuaqeeqimccse@sina.com

---

• Oncology

OBJECTIVE: Mammalian target of rapamycin (mTOR) can negatively regulate cell autophagy, while its expression and activity are associated with the pathogenesis of osteosarcoma. MicroRNA 100 (MiR-100) down-regulation is associated with the pathogenesis and chemo-sensitivity of osteosarcoma. Bioinformatics analysis revealed the targeted relationship between miR-100 and the 3’-UTR of mTOR. We investigate the role of miR-100 in affecting mTOR expression, osteosarcoma cell autophagy, and sensitivity to cisplatin.

PATIENTS AND METHODS: MiR-100, mTOR, and Beclin-1 expressions in osteosarcoma tissue and normal control were compared. The relationship between miR-100 and mTOR was verified by dual luciferase assay. MiR-100, mTOR, and Beclin-1 levels in MG-63 cells and MG-63/DDP cells were tested. Cell apoptosis was determined by using flow cytometry. Cell malignancy was evaluated by colony formation assay.

RESULTS: MiR-100 and Beclin-1 significantly declined, while mTOR significantly increased in osteosarcoma tissue compared with that of normal tissue (p<0.05). MiR-100 targeting significantly inhibited mTOR expression compared to that of untreated (p<0.05). MiR-100 expression was down-regulated and mTOR level was elevated in MG-63/DDP cells compared with MG-63 cells (p<0.05). MG-63/DDP cells exhibited reduced cell autophagy and apoptosis, and enhanced colony formation induced by DDP. MiR-100 mimic and/or small interfere mTOR (si-mTOR) significantly promoted Beclin-1 expression, cell autophagy, and cell apoptosis, while attenuated colony formation.

CONCLUSIONS: MiR-100 declined, while mTOR up-regulated in osteosarcoma tissue. MiR-100 up-regulation enhanced cell autophagy and apoptosis induced by cisplatin via targeted inhibiting of mTOR.

Free PDF Download