RNA Modifications and Epigenetics in Modulation of Lung Cancer and Pulmonary Diseases

Abstract

Lung cancer is the leading cause of cancer-related mortality worldwide, and its tumorigenesis involves the accumulation of genetic and epigenetic events in the respiratory epithelium. Epigenetic modifications, such as DNA methylation, RNA modification, and histone modifications, have been widely reported to play an important role in lung cancer development and in other pulmonary diseases. Whereas the functionality of DNA and chromatin modifications referred to as epigenetics is widely characterized, various modifications of RNA nucleotides have recently come into prominence as functionally important. N6-methyladosine (m6A) is the most prevalent internal modification in mRNAs, and its machinery of writers, erasers, and readers is well-characterized. However, several other nucleotide modifications of mRNAs and various noncoding RNAs have also been shown to play an important role in the regulation of biological processes and pathology. Such epitranscriptomic modifications play an important role in regulating various aspects of RNA metabolism, including transcription, translation, splicing, and stability. The dysregulation of epitranscriptomic machinery has been implicated in the pathological processes associated with carcinogenesis including uncontrolled cell proliferation, migration, invasion, and epithelial-mesenchymal transition. In recent years, with the advancement of RNA sequencing technology, high-resolution maps of different modifications in various tissues, organs, or disease models are being constantly reported at a dramatic speed. This facilitates further understanding of the relationship between disease development and epitranscriptomics, shedding light on new therapeutic possibilities. In this review, we summarize the basic information on RNA modifications, including m6A, m1A, m5C, m7G, pseudouridine, and A-to-I editing. We then demonstrate their relation to different kinds of lung diseases, especially lung cancer. By comparing the different roles RNA modifications play in the development processes of different diseases, this review may provide some new insights and offer a better understanding of RNA epigenetics and its involvement in pulmonary diseases.

A Prognostic Risk Score Based on Hypoxia-, Immunity-, and Epithelialto-Mesenchymal Transition-Related Genes for the Prognosis and Immunotherapy Response of Lung Adenocarcinoma

“…In this study, stemness-related biomarkers were positively associated with the risk score, demonstrating the prognostic value of the formula. Modification of m 6 A, m 5 C, m 1 A, and m 7 G are the common type of modification in RNA and plays critical roles in cancer development ( Teng et al, 2021 ; Xu F. et al, 2021 ; Xu R. et al, 2021 ). And RNA methylation highly interconnected with hypoxia, immune response and EMT( Lin et al, 2019 ; Chao et al, 2020 ; Wang E. et al, 2021 ).…”

Transcriptome Profiling of N7-Methylguanosine Modification of Messenger RNA in Drug-Resistant Acute Myeloid Leukemia

“…Recently, m7G methylation modifications have attracted increasing attention. Methyltransferase-like 1 (METTL1) is a writer of m7G methylation ( 30 ). Recent studies also reported that METTL1 is involved in tumor development by promoting mRNA processing in an m7G-dependent manner ( 31 ).…”

Construction of an m6A-related lncRNA model for predicting prognosis and immunotherapy in patients with lung adenocarcinoma

“…M6A modification, the most common epigenetic methylation modification in mammalian mRNA and lncRNA, participates in almost every process of RNA metabolism (Dai et al 2018). Convincing evidence indicated that m6Amodification of lncRNAs plays a critical regulatory role in the development and progression of lung cancer (Teng et al 2021). For example, ALKBH5-mediated m6A demethylation of lncRNA RMRP promotes tumorigenesis of LUAD in vitro and in vivo (Yu and Zhang 2021).…”