Abstract
Increasing evidence has indicated that lncRNAs acting as competing endogenous RNAs (ceRNAs) play crucial roles in tumorigenesis, metastasis and diagnosis of cancer. However, the function of lncRNAs as ceRNAs involved in esophageal squamous cell carcinoma (ESCC) is still largely unknown. In this study, clinical implications of two intrinsic subtypes of ESCC were identified based on expression profiles of lncRNA and mRNA. ESCC subtype-specific differential co-expression networks between mRNAs and lncRNAs were constructed to reveal dynamic changes of their crosstalks mediated by miRNAs during tumorigenesis. Several well-known cancer-associated lncRNAs as the hubs of the two networks were firstly proposed in ESCC. Based on the ceRNA mechanism, we illustrated that the“loss” of miR-186-mediated PVT1-mRNA and miR-26b-mediated LINC00240-mRNA crosstalks were related to the two ESCC subtypes respectively. In addition, crosstalks between LINC00152 and EGFR, LINC00240 and LOX gene family were identified, which were associated with the function of “response to wounding” and “extracellular matrix-receptor interaction”. Furthermore, functional cooperation of multiple lncRNAs was discovered in the two differential mRNA-lncRNA crosstalk networks. These together systematically uncovered the roles of lncRNAs as ceRNAs implicated in ESCC.
Highlights
In the past decade, research on the non-coding RNA has gained widespread attention. lncRNAs are a large class of non-coding RNAs, which are longer than 200 nucleotides and pervasively transcribed in the genome
We performed an unsupervised hierarchical clustering analysis based on the expression of mRNAs and lncRNAs of 119 esophageal squamous cell carcinoma (ESCC) patients
Molecular classification of ESCC based on mRNA-lncRNA expression data has never been reported
Summary
Research on the non-coding RNA has gained widespread attention. lncRNAs are a large class of non-coding RNAs, which are longer than 200 nucleotides and pervasively transcribed in the genome. Research on the non-coding RNA has gained widespread attention. LncRNAs are a large class of non-coding RNAs, which are longer than 200 nucleotides and pervasively transcribed in the genome. Dysregulation of lncRNAs are associated with different types of cancers, and lncRNAs as reliable biomarkers for cancers are identified [2,3,4]. Recent whole-genome and whole-exome sequencing on ESCC patients revealed six well-known tumor-associated genes (TP53, CDKN2A etc.) and two novel oncogenes (ADAM29 and FAM135B) [8]. In noncoding RNA research, miRNAs (miR-20 and miR-21 etc.) and lncRNAs (HOTAIR and H19 etc.) as oncogenes or tumor suppressors were studied in the development of ESCC [9,10,11]. Even so, compared to coding genes and miRNAs, dysregulated lncRNAs implicated in ESCC remain little known
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