MiR-6124: A potential new prognosis biomarker for lung squamous cell carcinoma through m5C regulating mechanism.

Abstract

e20568 Background: RNA methylation is an important epigenetic modification that can act as tumor prognosis biomarkers, and which is regulated by methyltransferase, RNA binding protein, and demethylase. 5-Methylcytosine (m5C) is a well-known post-transcriptional modification that plays an important role in cell differentiation and apoptosis. Although gene mutations in those regulator genes are associated with various cancers, the m5C regulating mechanism and its roles in cancer prognosis largely remains unknown. This study aimed to find new microRNA biomarkers associated with prognosis of clinical outcomes through m5C regulating mechanism in lung squamous cell carcinoma (LUSC). Methods: The RNA-seq expression data of LUSC were collected from the The Cancer Genome Atlas (TCGA). In total, we obtained 501 LUSC tumor samples and 49 normal samples from 502 LUSC patients. We firstly identified differential expressed genes of the 13 previously reported m5C regulators between the tumor tissues and adjacent normal tissues. Then miRNAs were identified using Pearson correlation analysis between the microRNA expression and the differential expressed m5C regulator genes. Pathway enrichment analysis of the miRNAs was performed using clusterProfiler to examine their cancer development roles. Furthermore, cox regression analysis was used to evaluate the risk factor for overall survival. Targeted relationship between miRNA and genes were confirmed by miRTarBase. Results: Differential analysis revealed 4 significantly up-regulated (NOP2, NSUN2, DNMT3B and ALYREF) genes in tumor among 13 interested m5C regulators. Pearson correlation analysis identified 39 correlated miRNAs. After cox regression, we found out one micro-RNA miR-6124, which is highly correlated with DNMT3B gene and is significantly associated with worse overall survival (OS, p < 0.01). We then identified the regulatory targets of miR-6124 using miRTarBase database. In total we identified 181 target genes. Among them, H3F3A which encode histone H3 synergistically work with DNMT3B gene as showed in the previous studies and promote DNA methylation of the oncogenes. Such preliminary results showed miR-6124 may be involved in cancer pathway regulating and was a potential prognosis biomarker candidate in LUSC. Conclusions: We identified a potential new prognosis biomarker in lung squamous cell carcinoma. The identified miR-6124 is involved in DNMT3B and m5C regulating mechanism. Further evidences are needed to study its’ role in clinical applications.