NSUN2, also known as NOP2/Sun RNA methyltransferase family member 2, is a key enzyme in 5-methylcytosine (m5C) RNA modification. It methylates multiple RNA species, including tRNAs, mRNAs, and non-coding RNAs, influencing RNA stability, translation efficiency, and cellular stress responses. This modification is involved in various biological processes such as cell proliferation, differentiation, and survival, and is associated with multiple cancer-related signaling pathways [3,4].

Genetic deletion of the glucose/NSUN2/TREX2 axis suppresses tumorigenesis and overcomes anti-PD-L1 immunotherapy resistance in "cold" tumors through cGAS/STING activation [1]. In EGFR-mutant non-small-cell lung cancer, genetic inhibition of NSUN2 led to tumor regression and overcame intrinsic resistance to gefitinib [2]. Silencing NSUN2 suppressed esophageal squamous cell carcinoma (ESCC) tumorigenesis and progression in Nsun2 knockout mouse models [6]. Also, in endometrial cancer, targeting the NSUN2/SLC7A11 axis inhibited tumor growth by increasing lipid peroxidation and ferroptosis [5].

In conclusion, NSUN2 is crucial for maintaining m5C RNA methylation, which impacts various biological processes. Gene knockout models, especially in cancer research, have revealed that NSUN2 plays significant roles in tumorigenesis, tumor progression, and drug resistance. Understanding NSUN2 provides insights into disease mechanisms and potential therapeutic targets.