MicroRNA-199b-5p is involved in the Notch signaling pathway in osteosarcoma

• Published in: Human pathology 2013-08, Vol.44 (8), p.1648-1655
• Main Authors: Won, Kyu Yeoun, MD, PhD, Kim, Youn Wha, MD, PhD, Kim, Hyun-Sook, MS, Lee, Seung Kwan, PhD, Jung, Woon-Won, PhD, Park, Yong-Koo, MD, PhD
• Format: Article
• Language: English
• Subjects: Adult; Aged; Apoptosis; Bone cancer; Bone Neoplasms - genetics; Cell growth; Deregulation; Female; Gene expression; Gene Expression Regulation, Neoplastic - genetics; Humans; Kinases; Male; MicroRNA; MicroRNAs - genetics; Middle Aged; miR-199b-5p; Notch pathway; Oligonucleotide Array Sequence Analysis; Osteosarcoma; Osteosarcoma - genetics; Pathology; Polymerase chain reaction; Proteins; Real-Time Polymerase Chain Reaction; Receptors, Notch - genetics; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction - genetics; Studies; Tumors
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/j.humpath.2013.01.016

Summary MicroRNAs (miRNAs) play important roles in the development, differentiation, and function of different cell types and in the pathogenesis of various human diseases. miRNAs are differentially expressed in normal and cancer cells. The investigation of miRNA expression between healthy subjects and patients with osteosarcoma is crucial for future clinical trials. We performed miRNA microarray analysis on 8 formalin-fixed, paraffin-embedded osteosarcoma tissue samples. We confirmed the results of the microarray analysis using reverse transcription polymerase chain reaction. miRNA profiling of osteosarcoma tissue samples showed that expression of 10 miRNAs had increased 10-fold compared with normal controls. Among the 10 miRNAs, 3 miRNAs (miR-199b-5p, miR-338-3p, and miR-891a) were confirmed to have been up-regulated by reverse transcription polymerase chain reaction. After transfection of 4 osteosarcoma cell lines with miR-199b-5p inhibitor, the expression of Notch pathway components in the transfected cell lines was changed. These results revealed that miR-199b-5p plays a role in Notch signaling in osteosarcoma. Recently, the inhibition of Notch and HES1 signaling has been suggested as a potential therapeutic strategy to prevent metastasis in human osteosarcoma. Taken together with our results, we suggest that miR-199b-5p inhibitor may also be a therapeutic option for osteosarcoma.