N⁶-methyladenosine (m⁶A) modification is a dynamic, reversible process and is the most prevalent internal modification of RNA. This modification is regulated by three protein groups: methyltransferases (“writers”), demethylases (“erasers”), and m⁶A-binding proteins (“readers”). m⁶A modification and related enzymes could represent an optimal strategy to deepen the epigenetic mechanism. Numerous reports have suggested that aberrant modifications of m⁶A lead to aberrant expression of important viral genes. Here, we review the role of m⁶A modifications in viral replication and virus–host interactions. In particular, we focus on DNA and RNA viruses associated with human diseases, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human immunodeficiency virus (HIV)-1, Epstein–Barr virus (EBV), and Kaposi’s sarcoma-associated herpesvirus (KSHV). These findings will contribute to the understanding of the mechanisms of virus–host interactions and the design of future therapeutic targets for treatment of tumors associated with viral infections.

Colorectal cancer is one of the most common malignant tumors in the digestive system, and its high incidence and metastasis rate make it a terrible killer that threatens human health. In-depth exploration of the targets affecting the progression of colorectal cancer cells and the development of specific targeted drugs for them are of great significance for the prognosis of colorectal cancer patients. Erythropoietin-producing hepatocellular A2 (EphA2) is a member of the Eph subfamily with tyrosine kinase activity, plays a key role in the regulation of signaling pathways related to the malignant phenotype of various tumor cells, but its specific regulatory mechanism in colorectal cancer needs to be further clarified. Here, we found that EphA2 was abnormally highly expressed in colorectal cancer and that patients with colorectal cancer with high EphA2 expression had a worse prognosis. We also found that EphA2 can form liquid-liquid phase separation condensates on cell membrane, which can be disrupted by ALW-II-41-27, an inhibitor of EphA2. In addition, we found that EphA2 expression in colorectal cancer was positively correlated with the expression of ferroptosis-related genes and the infiltration of multiple immune cells. These findings suggest that EphA2 is a novel membrane protein with phase separation ability and is associated with ferroptosis and immune cell infiltration, which further suggests that malignant progression of colorectal cancer may be inhibited by suppressing the phase separation ability of EphA2.

As a well-established member of a strongly conserved protein family, DDX5 binds to RNA helicase in a specific manner, which can regulate mRNA transcription, protein translation and synthesis and precursor messenger RNA processing or alternative splicing. The effects of DDX5 on carcinogenesis and cancer progression are increasingly evident. Circular RNAs (circRNAs), a novel group of functionally non-coding RNAs (ncRNAs) with disordered expression, are associated with various pathological processes (e.g., tumors). circRNA pattern and its function regulated by DDX5 have not yet been determined. According to our findings, DDX5 was dramatically upregulated for stomach cancer tissues, and its overexpression contributed to the cell growth and invasion of GC cells. Based on the analysis of genome-wide circRNAs conducted with circRNA sequencing, DDX5 induces a large number of circRNAs. Further to screen several circRNAs from PHF14 for function, it was found that circPHF14 was essential for the growth and tumorigenesis of DDX5-positive gastric cancer cells. These findings suggest that in addition to the messenger RNA and microRNA patterns, DDX5 also effects a circRNA pattern, as demonstrated by circPHF14. DDX5-induced circRNAs have been found to be of crucial importance for the growth of DDX5-positive gastric cancer cells, providing a new therapeutic target.