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 like tRNAs, mRNAs, and non-coding RNAs, influencing RNA stability, translation efficiency, and cellular stress responses, thus playing a significant role in various biological processes such as cell proliferation, differentiation, and survival [3].

In cancer research, genetic deletion of the glucose/NSUN2/TREX2 axis in "cold tumors" suppresses tumorigenesis and overcomes anti-PD-L1 immunotherapy resistance 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]. In endometrial cancer, knockdown of NSUN2 in vitro and in vivo increased lipid peroxidation and ferroptosis, inhibiting tumor growth [4]. In osteosarcoma, knocking down NSUN2 could counterbalance its promoting effect on cancer cell progression [5]. In esophageal squamous cell carcinoma, silencing NSUN2 suppressed tumorigenesis and progression in Nsun2 knockout mouse models [6].

In conclusion, NSUN2 is crucial for maintaining m5C RNA methylation, which impacts multiple biological processes. Its role in promoting tumorigenesis and conferring therapy resistance in various cancers, as revealed by gene knockout models, highlights its potential as a biomarker for cancer diagnosis, prognosis, and a therapeutic target.