N⁶‐Methyladenosine‐Modified CBX1 Regulates Nasopharyngeal Carcinoma Progression Through Heterochromatin Formation and STAT1 Activation

Abstract Epitranscriptomic remodeling such as N⁶‐methyladenosine (m⁶A) modification plays a critical role in tumor development. However, little is known about the underlying mechanisms connecting m⁶A modification and nasopharyngeal carcinoma (NPC) progression. Here, CBX1 is identified, a histone methylation regulator, to be significantly upregulated with m⁶A hypomethylation in metastatic NPC tissues. The m⁶A‐modified CBX1 mRNA transcript is recognized and destabilized by the m⁶A reader YTHDF3. Furthermore, it is revealed that CBX1 promotes NPC cell migration, invasion, and proliferation through transcriptional repression of MAP7 via H3K9me3‐mediated heterochromatin formation. In addition to its oncogenic effect, CBX1 can facilitate immune evasion through IFN‐γ‐STAT1 signaling‐mediated PD‐L1 upregulation. Clinically, CBX1 serves as an independent predictor for unfavorable prognosis in NPC patients. The results reveal a crosstalk between epitranscriptomic and epigenetic regulation in NPC progression, and shed light on the functions of CBX1 in tumorigenesis and immunomodulation, which may provide an appealing therapeutic target in NPC.