The novel interactions between microRNA expression, intercellular signaling and bone differentiation in osteosarcoma

Wednesday, September 24, 2014 — Poster Session IV
10:00 a.m. –12:00 p.m.	FAES Academic Center	NCI	CANCER-13

Authors

• Y. Jiang
• Y. Gindin
• P. Prancis
• S.Y. Moon
• S. Bilke
• S. Davis
• O.D
• Abaan
• R.L. Walker
• M. Pineda
• X.L. Li
• M. Subramanian
• Y.J. Zhu
• J. Knight
• J. Turner
• A. Lal
• P. Meltzer

Abstract

Osteosarcoma is the most common bone cancer in adolescents. Impaired differentiation of osteoblast cells is a distinguishing feature of this disease. For improvements in survival outcomes, better understanding of the bone differentiation program may provide new treatment approaches. To this end, we carried out the integrative computational analysis of mRNA and miRNA expression with CGH of 47 osteosarcoma and 20 osteoblast cell lines. Identified copy number gain and over-expression of miRNA-23a cluster in a substantial fraction of osteosarcoma samples. The miRNA-23a cluster is important for bone development. However, global changes in gene expression associated with functional gain of this cluster have not been fully explored. Experimental results show that over-expression of miR-23a delays ossification and calcification in osteosarcoma (HOS) cells. Downstream bioinformatic analysis identified miR-23a target gene Cx43, a mediator of intercellular signaling, affected by miR-23a levels. Connexin-43 is up-regulated in the course of HOS cell differentiation and is down-regulated in cells transfected with miR-23a. Analysis of gene expression data, reveals that Cx43 is consistently up-regulated during osteoblast differentiation. Suppression of Cx43 mRNA by miR-23a was confirmed in vitro using a luciferase reporter assay. This work demonstrates novel interactions between microRNA expression, intercellular signaling and bone differentiation in osteosarcoma

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