m5C Regulator-mediated methylation modification clusters contribute to the immune microenvironment regulation of multiple myeloma

Abstract

Background: Multiple myeloma (MM) is a hematological malignancy in which plasma cells proliferate abnormally. 5-methylcytosine (m5C) methylation modification is the primary epigenetic modification and is involved in regulating the occurrence, development, invasion, and metastasis of various tumors; however, its immunological functions have not been systematically described in MM. Thus, this study aimed to clarify the significance of m5C modifications and how the immune microenvironment is linked to m5C methylation in MM.Method: A total of 483 samples (60 healthy samples, 423 MM samples) from the Gene Expression Omnibus dataset were acquired to assess the expression of m5C regulators. A nomogram model was established to predict the occurrence of MM. We investigated the impact of m5C modification on immune microenvironment characteristics, such as the infiltration of immunocytes and immune response reactions. We then systematically evaluated three different m5C expression patterns to assess immune characteristics and metabolic functional pathways and established m5C-related differentially expressed genes (DEGs). In addition, biological process analysis was performed and an m5C score was constructed to identify potentially significant immunological functions in MM.Result: Differential expressions of m5C regulators were identified between healthy and MM samples. The nomogram revealed that m5C regulators could predict higher disease occurrence of MM. We identified three distinct m5C clusters with unique immunological and metabolic characteristics. Among the three different m5C clusters, cluster C had more immune characteristics and more metabolism-related pathways than clusters A and B. We analyzed 256 m5C-related DEGs and classified the samples into three different m5C gene clusters. Based on the m5C and m5C gene clusters, we calculated m5C scores and classified each patient into high- and low-m5C score groups.Conclusion: Our study demonstrated that m5C modification is involved in and contributes to the diversity and complexity of the immune microenvironment, which offers promise for the development of accurate therapeutic strategies.

Analysis of m7G methylation modification patterns and pulmonary vascular immune microenvironment in pulmonary arterial hypertension

“…However, the correlation between m 7 G and immune cells still requires further study. At present, the regulation of RNA methylation in diseases has been studied with m 6 A and m 5 C. M 5 C methylation can regulate tumor microenvironment infiltration characterization of lung adenocarcinoma and immune microenvironment of multiple myeloma (60,61). Interestingly, the m 6 A modulator may be a promising biomarker for the diagnosis and treatment of PAH in the monocrotaline-induced pulmonary hypertension model of rats (62)(63)(64).…”

The complex nature of lncRNA-mediated chromatin dynamics in multiple myeloma

“…Interestingly, NSUN2 has been reported as the sole writer of the m5C mark on lncRNAs (79). In MM, dysregulated deposition of RNA m5C has been correlated with disease progression and immune microenvironment regulation (102). Furthermore, recent studies have elucidated the importance of this modification in various other cancer types, including lung adenocarcinoma, pancreatic cancer, and colon cancer (79,(103)(104)(105).…”

Mitochondrial RNA modification: A novel therapeutic target to combat metastasis

“…In addition, m 6 A/m 5 C/m 1 A‐related lncRNAs are associated with the prognosis, immune microenvironment, and tumor mutational burden (TMB) of HNSCC (Wang et al, 2021). M 5 C modification contributes to the diversity and complexity of the immune microenvironment in multiple myeloma, which may provide a promising clue for immunotherapy (Ren et al, 2022). Moreover, the expression of two m 5 C regulators (NSUN3 and NSUN4) is positively correlated with the degree of infiltration of most immune cells and tumor purity in lung squamous cell carcinoma (LUSC) (Pan et al, 2021).…”

“…In addition, m 6 A/m 5 C/m 1 A-related lncRNAs are associated with the prognosis, immune microenvironment, and tumor mutational burden (TMB) of HNSCC (Wang et al, 2021). M 5 C modification contributes to the diversity and complexity of the immune microenvironment in multiple myeloma, which may provide a promising clue for immunotherapy (Ren et al, 2022). Moreover, the expression of two NSUN3 is the primary regulator for mitochondrial mRNA translation that promotes tumor metastasis; thus, the drugs that specifically inhibit mitochondrial translation without affecting cytoplasmic protein synthesis can be used to control metastasis.…”