MiR-138 Acts as a Tumor Suppressor by Targeting EZH2 and Enhances Cisplatin-Induced Apoptosis in Osteosarcoma Cells

• Published in: PloS one 2016-03, Vol.11 (3), p.e0150026-e0150026
• Main Authors: Zhu, Ziqiang, Tang, Jinshan, Wang, Jianqiang, Duan, Gang, Zhou, Lei, Zhou, Xiaoqing
• Format: Article
• Language: English
• Subjects: 3' Untranslated Regions; Analysis; Apoptosis; Apoptosis - drug effects; Assaying; Base Sequence; Biocompatibility; Biology and life sciences; Biomarkers; Biotechnology; Bone and Bones - metabolism; Bone and Bones - pathology; Bone cancer; Bone Neoplasms - genetics; Bone Neoplasms - pathology; Cancer therapies; Caspase; Caspase 3 - metabolism; Caspase-3; Cell growth; Cell Line, Tumor; Cell migration; Cell Movement; Cell Proliferation; Chemoresistance; Chemotherapy; Cisplatin; Cisplatin - toxicity; Disease prevention; Down-Regulation; Drug resistance; Enhancer of Zeste Homolog 2 Protein; Epigenetics; Health aspects; Humans; Influence; Kinases; Medical research; Medicine and Health Sciences; Metastasis; MicroRNA; MicroRNAs; MicroRNAs - chemistry; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; Orthopedics; Osteosarcoma; Osteosarcoma - genetics; Osteosarcoma - pathology; Osteosarcoma cells; Polycomb Repressive Complex 2 - antagonists & inhibitors; Polycomb Repressive Complex 2 - genetics; Polycomb Repressive Complex 2 - metabolism; Real-Time Polymerase Chain Reaction; Research and Analysis Methods; Sarcoma; Sequence Alignment; Surgery; Tissues; Tumor suppressor genes
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0150026

Chemotherapeutic insensitivity remains a major obstacle to treating osteosarcoma effectively. Recently, increasing evidence has suggested that microRNAs (miRNAs) are involved in drug resistance. However, the effect of miR-138 on cisplatin chemoresistance in osteosarcoma has not been reported. We used real-time PCR to detect the expression of mature miR-138 in osteosarcoma tissues and cell lines. Cell proliferation, invasion, and migration assays were used to observe changes to the osteosarcoma malignant phenotype. MiR-138 was downregulated in osteosarcoma tissues and cell lines, and miR-138 overexpression negatively regulated osteosarcoma cell proliferation, migration, and invasion. We also verified that EZH2 is a direct target of miR-138. Furthermore, enhancing EZH2 expression reduced the inhibitory effects of miR-138 on osteosarcoma. Proliferation, apoptosis assays and caspase-3 activity assay confirmed that elevated miR-138 expression enhanced osteosarcoma cell chemosensitivity to cisplatin by targeting EZH2. In conclusion, the present study demonstrates that miR-138 acts as a tumor suppressor by enhancing osteosarcoma cell chemosensitivity and supports its potential application for treating osteosarcoma in the future.