MicroRNA-199b-5p Is Involved in Notch Pathway of Osteosarcoma
Kyu Yeoun Won, Youn Wha Kim, Hyun-Sook Kim, Seung Kwan Lee, Woon-Won Jung, Yong-Koo Park. Kyung Hee University Hospital at Gangdong, Kyung Hee University, Seoul, Republic of Korea; College of Medicine, Kyung Hee University, Seoul, Republic of Korea; College of Health Science, Korea University, Seoul, Republic of Korea
Background: MicroRNAs (miRNA) play important roles in the development, differentiation and function of various cell types, and in the pathogenesis of various human diseases. The miRNAs are differentially expressed in normal cells and cancer cells. An investigation of miRNA expression between normal subjects and patients with osteosarcoma is a crucial step for future clinical trials.
Design: We performed a miRNA microarray analysis on 8 formalin fixed paraffin embedded osteosarcoma tissue samples. And we confirmed the result of microarray by reverse transcription polymerase chain reaction.
Results: The data from miRNA profiling of osteosarcoma indicated that 10 miRNAs showed 10-fold increased expression compared to normal control. Among the 10 miRNAs, three miRNAs (miR-199b-5p, miR-338-3p, and miR-891a) were confirmed with reverse transcription polymerase chain reaction. And through further cell line study, we identified that miR-199b-5p influenced the Notch pathway in osteosarcoma. After four osteosarcoma cell lines were transfected with miR-199b-5p inhibitor, the expressions of Notch pathway components (Dll1, JAG1, HES1, Dtx1) in transfected cell lines were changed in comparing with negative controls.
Conclusions: These results revealed that miR-199b-5p was involved in the Notch pathway of osteosarcoma. Recent study suggests that Notch and HES1 signaling may be a therapeutic target to prevent metastasis for human osteosarcoma patients using GSI (γ-secretase inhibitor). Taken together with our results, we suggest that miR-199b-5p inhibitor also may be a therapeutic option in osteosarcoma.
Category: Bone & Soft Tissue
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 5, Tuesday Afternoon