Reconstruction of lncRNA-miRNA-mRNA network based on competitive endogenous RNA reveals functional lncRNAs in skin cutaneous melanoma

Junyou Zhu,Jingling Zhao,Bin Shu,Jun Wu,Ning Liu,Lijun Zhang,Ruizhao Cai,Fei Zhou,Jin Deng,Shaohai Qi

doi:10.1186/s12885-020-07302-5

Abstract

BackgroundHuman skin cutaneous melanoma is the most common and dangerous skin tumour, but its pathogenesis is still unclear. Although some progress has been made in genetic research, no molecular indicators related to the treatment and prognosis of melanoma have been found. In various diseases, dysregulation of lncRNA is common, but its role has not been fully elucidated. In recent years, the birth of the “competitive endogenous RNA” theory has promoted our understanding of lncRNAs.MethodsTo identify the key lncRNAs in melanoma, we reconstructed a global triple network based on the “competitive endogenous RNA” theory. Gene Ontology and KEGG pathway analysis were performed using DAVID (Database for Annotation, Visualization, and Integration Discovery). Our findings were validated through qRT-PCR assays. Moreover, to determine whether the identified hub gene signature is capable of predicting the survival of cutaneous melanoma patients, a multivariate Cox regression model was performed.ResultsAccording to the “competitive endogenous RNA” theory, 898 differentially expressed mRNAs, 53 differentially expressed lncRNAs and 16 differentially expressed miRNAs were selected to reconstruct the competitive endogenous RNA network. MALAT1, LINC00943, and LINC00261 were selected as hub genes and are responsible for the tumorigenesis and prognosis of cutaneous melanoma.ConclusionsMALAT1, LINC00943, and LINC00261 may be closely related to tumorigenesis in cutaneous melanoma. In addition, MALAT1 and LINC00943 may be independent risk factors for the prognosis of patients with this condition and might become predictive molecules for the long-term treatment of melanoma and potential therapeutic targets.

Highlights

Human skin cutaneous melanoma is the most common and dangerous skin tumour, but its pathogenesis is still unclear
Identification of Differential expressed mRNAs (DEMs), differentially expressed lncRNAs (DELs) and differentially expressed miRNAs (DEMis) and reconstruction of the Long non-coding RNAs (lncRNA)-miRNA-mRNA network After standardization of the GEO datasets, 56, 70 and 34 DEMis between benign nevus tissues and primary melanoma tissues were identified in GSE24996, GSE35579 and GSE62372, respectively (Supplementary Table 2, Fig. 2a-f)
We ruled out two of these 18 DEMis, hsamiRNA-203a-3p and hsa-miRNA-1826, because no predicted gene was found in starBase according to method 2.3

Summary

Introduction

Human skin cutaneous melanoma is the most common and dangerous skin tumour, but its pathogenesis is still unclear. Some progress has been made in genetic research, no molecular indicators related to the treatment and prognosis of melanoma have been found. The birth of the “competitive endogenous RNA” theory has promoted our understanding of lncRNAs. Human skin cutaneous melanoma (SKCM) is the most common and dangerous type of skin tumour [1, 2]. Approximately 232,000 (1.7%) cases of cutaneous melanoma are reported among all newly diagnosed primary malignant cancers, and this disease results in approximately 55,500 cancer deaths (0.7% of all cancer deaths) [1, 3]. The high incidence and high mortality of melanoma indicate that researchers must further study this disease. Some achievements have been made in the genetic research of melanoma, markers related to diagnosis and treatment are needed

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