RNA methylation is a novel epigenetic modification that can be used to evaluate tumor prognosis. However, the underlying mechanisms are unclear. This study aimed to investigate the genetic characteristics of 5-methylcytosine (m5C) and N1-methyladenosine (m1A) regulators in lung squamous cell carcinoma (LUSC) and the prognostic value and immune-related effects of m5C regulators. To this end, we selected the public LUSC dataset from the Cancer Genome Atlas and Gene Expression Omnibus. The least absolute shrinkage and selection operator regression model was used to identify prognostic risk signatures. We used the UALCAN and Human Protein Atlas databases to study the expression of target gene mRNA/protein expression. Furthermore, the Tumor Immune Single Cell Hub and the Tumor Immune Estimation Resource were used to evaluate the degree of immune cell infiltration. Most of the m5C and m1A regulators showed significantly different expression between LUSC and normal samples. The m5C regulators were associated with poor prognosis. In addition, a prognostic risk signature was developed based on two m5C regulators, NOP2/Sun RNA methyltransferase 3 (NSUN3), and NOP2/Sun RNA methyltransferase 4 (NSUN4). Compared with normal lung tissues, the expression of NSUN3 and NSUN4 in the LUSC TCGA dataset was increased, which was related to clinicopathological characteristics and survival. NSUN3 and NSUN4 were related to the infiltration of six major immune cells; especially NSUN3, which was closely related to CD8+ T cells, while NSUN4 was closely related to neutrophils. Our findings suggest that m5C regulators can predict the clinical prognosis risk and regulate the tumor immune microenvironment in LUSC.
PurposeThe m5C RNA methylation regulators are closely related to tumor proliferation, occurrence, and metastasis. This study aimed to investigate the gene expression, clinicopathological characteristics, and prognostic value of m5C regulators in triple-negative breast cancer (TNBC) and their correlation with the tumor immune microenvironment (TIM).MethodsThe TNBC data, Luminal BC data and HER2 positive BC data set were obtained from The Cancer Genome Atlas and Gene Expression Omnibus, and 11 m5C RNA methylation regulators were analyzed. Univariate Cox regression and the least absolute shrinkage and selection operator regression models were used to develop a prognostic risk signature. The UALCAN and cBioportal databases were used to analyze the gene characteristics and gene alteration frequency of prognosis-related m5C RNA methylation regulators. Gene set enrichment analysis was used to analyze cellular pathways enriched by prognostic factors. The Tumor Immune Single Cell Hub (TISCH) and Timer online databases were used to explore the relationship between prognosis-related genes and the TIM.ResultsMost of the 11 m5C RNA methylation regulators were differentially expressed in TNBC and normal samples. The prognostic risk signature showed good reliability and an independent prognostic value. Prognosis-related gene mutations were mainly amplified. Concurrently, the NOP2/Sun domain family member 2 (NSUN2) upregulation was closely related to spliceosome, RNA degradation, cell cycle signaling pathways, and RNA polymerase. Meanwhile, NSUN6 downregulation was related to extracellular matrix receptor interaction, metabolism, and cell adhesion. Analysis of the TISCH and Timer databases showed that prognosis-related genes affected the TIM, and the subtypes of immune-infiltrating cells differed between NSUN2 and NSUN6.ConclusionRegulatory factors of m5C RNA methylation can predict the clinical prognostic risk of TNBC patients and affect tumor development and the TIM. Thus, they have the potential to be a novel prognostic marker of TNBC, providing clues for understanding the RNA epigenetic modification of TNBC.
Erianthus arundinaceus is a valuable source of agronomic traits for sugarcane improvement such as ratoonability, biomass, vigor, tolerance to drought and water logging, as well as resistance to pests and disease. To investigate the introgression of the E. arundinaceus genome into sugarcane, five intergeneric F1 hybrids between S. officinarum and E. arundinaceus and 13 of their BC1 progeny were studied using the genomic in situ hybridization (GISH) technique. In doing so, we assessed the chromosome composition and chromosome transmission in these plants. All F1 hybrids were aneuploidy, containing either 28 or 29 E. arundinaceus chromosomes. The number of E. arundinaceus chromosomes in nine of the BC1 progeny was less than or equal to 29. Unexpectedly, the number of E. arundinaceus chromosomes in the other four BC1 progeny was above 29, which was more than in their F1 female parents. This is the first cytogenetic evidence for an unexpected inheritance pattern of E. arundinaceus chromosomes in sugarcane. We pointed to several mechanisms that may be involved in generating more than 2n gametes in the BC1 progeny. Furthermore, the implication of these results for sugarcane breeding programs was discussed.
Long non-coding RNAs (lncRNAs), which are involved in the regulation of RNA methylation, can be used to evaluate tumor prognosis. lncRNAs are closely related to the prognosis of patients with lung adenocarcinoma (LUAD); thus, it is crucial to identify RNA methylation-associated lncRNAs with definitive prognostic value. We used Pearson correlation analysis to construct a 5-Methylcytosine (m5C)-related lncRNAs–mRNAs coexpression network. Univariate and multivariate Cox proportional risk analyses were then used to determine a risk model for m5C-associated lncRNAs with prognostic value. The risk model was verified using Kaplan–Meier analysis, univariate and multivariate Cox regression analysis, and receiver operating characteristic curve analysis. We used principal component analysis and gene set enrichment analysis functional annotation to analyze the risk model. We also verified the expression level of m5C-related lncRNAs in vitro. The association between the risk model and tumor-infiltrating immune cells was assessed using the CIBERSORT tool and the TIMER database. Based on these analyses, a total of 14 m5C-related lncRNAs with prognostic value were selected to build the risk model. Patients were divided into high- and low-risk groups according to the median risk score. The prognosis of the high-risk group was worse than that of the low-risk group, suggesting the good sensitivity and specificity of the constructed risk model. In addition, 5 types of immune cells were significantly different in the high-and low-risk groups, and 6 types of immune cells were negatively correlated with the risk score. These results suggested that the risk model based on 14 m5C-related lncRNAs with prognostic value might be a promising prognostic tool for LUAD and might facilitate the management of patients with LUAD.
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