Research Papers:

Comprehensive analysis of mRNA-lncRNA co-expression profile revealing crucial role of imprinted gene cluster DLK1-MEG3 in chordoma

Hao Chen, Kai Zhang, Jian Lu, Guizhong Wu, Huilin Yang and Kangwu Chen _

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Oncotarget. 2017; 8:112623-112635. https://doi.org/10.18632/oncotarget.22616

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Hao Chen1,*, Kai Zhang1,*, Jian Lu1, Guizhong Wu1, Huilin Yang1,2 and Kangwu Chen1

1Department of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China

2Institute of Orthopedics, Soochow University, Suzhou, Jiangsu 215006, P.R. China

*These authors contributed equally to this work

Correspondence to:

Kangwu Chen, email: kangwuchen2008@hotmail.com

Huilin Yang, email: suzhouspine@hotmail.com

Keywords: chordoma, long non-coding RNA, protein coding gene, imprinted gene cluster, DLK1-MEG3

Received: February 08, 2017     Accepted: September 03, 2017     Published: November 08, 2017


Chordoma is a rare bone tumor with high recurrence rate, but the mechanism of its development is unclear. Long non-coding RNAs(lncRNAs) are recently revealed to be regulators in a variety of biological processed by targeting on mRNA transcription. Their expression profile and function in chordoma have not been investigated yet. In this study, we firstly performed the comprehensive analysis of the lncRNA and coding genes expression analysis with three chordoma samples and three fetal nucleus pulposus tissues. lncRNA and gene microarrays were used to determine the differentially expressed lncRNAs and protein coding genes. 2786 lncRNAs and 3286 coding genes were significantly up-regulated in chordoma, while 2042 lncRNAs and 1006 coding genes were down-regulated. Pearson correlation analysis was conducted to correlate differentially expressed lncRNAs with protein coding genes, indicating a comprehensive lncRNA-coding gene co-expression network in chordoma. Cis-correlation analysis showed that various transcripts of MEG3 and MEG8 were paired with the most differentially expressed gene DLK1. As located in the same locus, we further analyzed the miRNA clusters in this region, and identified that 61.22% of these miRNAs were significantly down-regulated, implying the silence of the imprinted gene cluster DLK1-MEG3. Overexpression of MEG3 suppressed the proliferation of chordoma cells. Our study pointed out the potential role of lncRNAs in chordoma, presented the lncRNA-coding genes co-expression profile, and revealed that imprinted gene cluster DLK1-MEG3 contributes to the pathogenesis of chordoma development.

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