Circular RNA circ_0102049 promotes cell progression as ceRNA to target MDM2 via sponging miR-1304-5p in osteosarcoma

• Published in: Pathology, research and practice research and practice, 2019-12, Vol.215 (12), p.152688-152688, Article 152688
• Main Authors: Jin, Yan, Li, Lisen, Zhu, Tongtong, Liu, Guangyao
• Format: Article
• Language: English
• Subjects: Adult; Apoptosis; Bone Neoplasms - genetics; Bone Neoplasms - metabolism; Bone Neoplasms - mortality; Bone Neoplasms - pathology; Cell Line, Tumor; Cell Movement; Cell Proliferation; Circ_0102049; Circular RNA; Female; Gene Expression Regulation, Neoplastic; Humans; Male; MDM2; MicroRNAs - genetics; MicroRNAs - metabolism; miR-1304-5p; Neoplasm Invasiveness; Osteosarcoma; Osteosarcoma - genetics; Osteosarcoma - metabolism; Osteosarcoma - mortality; Osteosarcoma - pathology; Proto-Oncogene Proteins c-mdm2 - genetics; Proto-Oncogene Proteins c-mdm2 - metabolism; RNA, Circular - genetics; RNA, Circular - metabolism; Signal Transduction; Tumor Burden
• ISSN: 0344-0338; 1618-0631
• DOI: 10.1016/j.prp.2019.152688

Osteosarcoma (OS) is known as a tumor that derives from skeletal system with increasing incidence worldwide. This study aimed to explore the effect of a circular RNA (circRNA), circ_0102049, on OS and reveal its potential molecular mechanism. In this work, the expression of circ_0102049 was detected by quantitative real time polymerase chain reaction (qRT-RCR) in both OS specimens and cell lines. The relationship between circ_0102049 level and patients’ overall survival was evaluated by Kaplan-Meier curves and Cox regression analysis. Cell proliferation, apoptosis, migration and invasion of U2OS and MG63 cells were measured by cell counting kit-8 (CCK-8), flow cytometry, wound healing and transwell experiments, respectively. In addition, subcellular fractionation, bioinformatics analysis and dual-luciferase reporter assay were utilized to reveal the mechanism of circ_0102049 in OS. Circ_0102049 was overexpressed in both OS specimens and cells. Moreover, the level of circ_0102049 in OS patients was markedly correlated with larger tumor size, pulmonary metastasis and poor prognosis. Circ_0102049 remarkably accelerated cell proliferation, migration and invasion but attenuated cell apoptosis in OS cells analyzed by gain/loss of function experiments. What’s more, we identified that circ_0102049 functions as a competing endogenous RNA (ceRNA) to competitively sponge miR-1304-5p to upregulate MDM2 expression at posttranscriptional level, thus mediating the cellular behaviors of OS cells. Collectively, our study provides an innovatively regulatory mechanism of circ_0102049 in OS and points out a new way for OS treatment.