A comprehensive genome-wide analysis of the long noncoding RNA expression profile in metastatic lymph nodes of oral mucosal melanoma

Abstract

Background & aim: Oral mucosal melanoma (OMM) is a kind of malignancy with extremely rare morbidity. It exhibits a poorer biological behavior and clinical outcome compared with cutaneous melanoma. lncRNAs are endogenous cellular RNA transcripts with no protein-coding potential and are associated with oncogenesis through cis- or trans-acting mechanisms. Despite increased evidence that proved lncRNAs have vital roles in tumorigenesis of mucosal melanoma, little is known about their functions in the progress of lymph node dissemination of OMM.

Method: Here, we constructed a lncRNA and mRNA microarray using six metastatic lymph nodes and paired-matched non-metastatic lymph nodes. Then, we performed RT-PCR to validate the microarray data both in primary and metastases. We further constructed lncRNA and mRNA co-expressing networks and analyzed the biological functions by Gene Ontology (GO) and pathway analyses for dysregulated lncRNAs and mRNAs. Cis- and trans-regulation analysis were also performed to explore the specific mechanism of lncRNAs in OMM.

Result: Our results showed that 570 lncRNAs were upregulated with 292 lncRNAs downregulated in the metastatic OMM tissues. The results of RT-PCR were consistent with our microarray dataset both in primary and metastases. Gene Ontology (GO) and pathway analyses indicated that they play an important role in the melanin biosynthetic process, new growing cell tip and lysosomes in metastatic OMM. In the cis-regulation analysis, we observed metastasis-associated gene, PLEKHA5, the cis gene of lnc-AEBP2-1_1 and lnc-AEBP2-2_1, and microphthalmia-associated transcription factor (MITF), the cis gene of SAMMSON_3, SAMMSON_5 and lnc-MITF-5_1. In the trans-regulation analysis, CTBP2 and SUZ12 regulated lncRNA expression in the core TF-lncRNA-gene network.

Conclusion: Our results suggest that lncRNAs may be involved in the metastasis of OMM, and further investigation is needed to focus on the biological functions and the underlining molecular mechanisms exerted by these dysregulated lncRNAs in OMM.

Keywords: Lymph nodes; Metastasis; Oral mucosal melanoma; lncRNAs.