Identification of the miRNA-mRNA regulatory network of small cell osteosarcoma based on RNA-seq
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Lin Xie1,2,*, Yedan Liao2,*, Lida Shen2, Fengdi Hu2, Sunlin Yu2, Yonghong Zhou2, Ya Zhang1, Yihao Yang1, Dongqi Li1, Minyan Ren2, Zhongqin Yuan2 and Zuozhang Yang1
1Bone and Soft Tissue Tumors Research Center of Yunnan Province, Department of Orthopedics, The Third Affiliated Hospital of Kunming Medical University, Tumor Hospital of Yunnan Province, Kunming, Yunnan 650118, China
2Department of Medical Oncology, The Third Affiliated Hospital of Kunming Medical University, Tumor Hospital of Yunnan Province, Kunming, Yunnan 650118, China
*These authors contributed equally to this work and are co-first authors
Keywords: small cell osteosarcoma, RNA-seq, microRNA, regulatory network
Received: March 06, 2017 Accepted: April 07, 2017 Published: April 18, 2017
Small cell osteosarcoma (SCO) is a rare subtype of osteosarcoma characterized by highly aggressive progression and a poor prognosis. The miRNA and mRNA expression profiles of peripheral blood mononuclear cells (PBMCs) were obtained in 3 patients with SCO and 10 healthy individuals using high-throughput RNA-sequencing. We identified 37 dysregulated miRNAs and 1636 dysregulated mRNAs in patients with SCO compared to the healthy controls. Specifically, the 37 dysregulated miRNAs consisted of 27 up-regulated miRNAs and 10 down-regulated miRNAs; the 1636 dysregulated mRNAs consisted of 555 up-regulated mRNAs and 1081 down-regulated mRNAs. The target-genes of miRNAs were predicted, and 1334 negative correlations between miRNAs and mRNAs were used to construct an miRNA-mRNA regulatory network. Dysregulated genes were significantly enriched in pathways related to cancer, mTOR signaling and cell cycle signaling. Specifically, hsa-miR-26b-5p, hsa-miR-221-3p and hsa-miR-125b-2-3p were significantly dysregulated miRNAs and exhibited a high degree of connectivity with target genes. Overall, the expression of dysregulated genes in tumor tissues and peripheral blood samples of patients with SCO measured by quantitative real-time polymerase chain reaction corroborated with our bioinformatics analyses based on the expression profiles of PBMCs from patients with SCO. Thus, hsa-miR-26b-5p, hsa-miR-221-3p and hsa-miR-125b-2-3p may be involved in SCO tumorigenesis.
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