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

  • Adv Sci (Weinh). 2022 Oct 30;e2205091. doi: 10.1002/advs.202205091.
Yin Zhao  1 ,  Shengyan Huang  1 ,  Xirong Tan  1 ,  Liufen Long  1 ,  Qingmei He  1 ,  Xiaoyu Liang  1 ,  Jiewen Bai  1 ,  Qingjie Li  1 ,  Jiayi Lin  1 ,  Yingqin Li  1 ,  Na Liu  1 ,  Jun Ma  1 ,  Yupei Chen  1
Affiliations
  • 1. Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, 651 Dongfeng Road East, Guangzhou, Guangdong, 510060, China.
PMID: 36310139 DOI: 10.1002/advs.202205091
Abstract

Epitranscriptomic remodeling such as N6 -methyladenosine (m6 A) modification plays a critical role in tumor development. However, little is known about the underlying mechanisms connecting m6 A modification and nasopharyngeal carcinoma (NPC) progression. Here, CBX1 is identified, a histone methylation regulator, to be significantly upregulated with m6 A hypomethylation in metastatic NPC tissues. The m6 A-modified CBX1 mRNA transcript is recognized and destabilized by the m6 A 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.

Keywords
CBX1; MAP7; PD-L1; heterochromatin; m6A; nasopharyngeal carcinoma.
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