Identification of the miRNA-mRNA regulatory network of small cell osteosarcoma based on RNA-seq

Abstract

// Lin Xie 1, 2, * , Yedan Liao 2, * , Lida Shen 2 , Fengdi Hu 2 , Sunlin Yu 2 , Yonghong Zhou 2 , Ya Zhang 1 , Yihao Yang 1 , Dongqi Li 1 , Minyan Ren 2 , Zhongqin Yuan 2 and Zuozhang Yang 1 1 Bone 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 2 Department 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 Correspondence to: Zuozhang Yang, email: yangzuozhang@163.com , zuozhangyang1326@sohu.com Keywords: small cell osteosarcoma, RNA-seq, microRNA, regulatory network Received: March 06, 2017      Accepted: April 07, 2017      Published: April 18, 2017 ABSTRACT 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.