Identification of m7G Methylation-Related miRNA Signature Associated with Survival and Immune Microenvironment Regulation in Uterine Corpus Endometrial Carcinoma

Abstract

Background. N7-methylguanosine (m7G) has been implicated in the development of cancer. The role of m7G-related miRNAs in the survival prediction of UCEC patients has not been investigated. Current research was the first to construct an m7G-related miRNA model to accurately predict the survival of patients with uterine corpus endometrial carcinoma (UCEC) and to explore immune cell infiltration and immune activity in the tumor microenvironment. Methods. RNA-seq data and clinical information of UCEC patients were derived from The Cancer Genome Atlas (TCGA) database. Using the TargetScan online database, we predicted miRNAs linked to the m7G-related genes and identified miRNAs which were significantly associated with the survival in UCEC patients and constructed a risk scoring model. The TCGA-UCEC cases were scored according to the risk model, and the high- and low-risk groups were divided by the median risk value. Gene enrichment analysis and immune cell infiltration and immune function analysis were performed using “clusterProfiler” and “GSVA” packages in R. Results. The survival prediction model consisted of 9 miRNAs, namely, hsa-miR-1301, hsa-miR-940, hsa-miR-592, hsa-miR-3170, hsa-miR-876, hsa-miR-215, hsa-miR-934, hsa-miR-3920, and hsa-miR-216b. Survival of UCEC patients in the high-risk group was worse than that in the low-risk group ( p < 0.001 ). The receiver operating characteristic (ROC) curve showed that the model had good predictive performance, and the area under the curve was 0.800, 0.690, and 0.705 for 1-, 3-, and 5-year survival predictions, respectively. There were differences in the degree of immune cell infiltration and immune activity between the low-risk and high-risk groups. The expression levels of the identified differentially expressed genes correlated with the susceptibility to multiple anticancer drugs. Conclusions. The survival prediction model constructed based on 9 m7G-related miRNAs had good predictive performance.

RNA N6-methyladenosine modification in female reproductive biology and pathophysiology

“…m 7 G modification is usually catalysed by METTL1 and located at the 5' caps and internal positions of eukaryotic mRNA [152]. Several studies on endometrial cancer have found that m 1 A-and m 7 G-related lncRNAs and miRNAs can be used to construct tumour-related prognostic models and are associated with different immune infiltration phenotypes and drug susceptibility in endometrial cancer [153][154][155][156]. Pseudouridine is the most abundant modified nucleotide in RNA [157].…”

The interplay of sex steroid hormones and microRNAs in endometrial cancer: current understanding and future directions

“…As tumor-causing factors, several miRNAs have been identified as potential biomarkers and regulators of EC (Figure 2). miRNAs such as miR-130, miR-200a, miR-429, miR-107 5p, miR-21, miR-125b, miR-101, miR-27a-5p, miR-576-5p, miR-210-3p, miR-1903p, miR-18a-5p, miR-103, miR 215, miR-27a, miR-34a-5p, miR-146-5p, miR-423, and miR-302 have been shown to play different roles in promoting or suppressing EC progression by targeting various genes and signaling pathways (83-87, 90,91,95,97,101,103,124,138,200). These findings provide potential targets for diagnosis, prognosis, and therapeutic interventions in EC.…”