Basic Science Spotlight

RNA Hypomethylation of CBX1 Contributes to NPC Progression by Promoting Histone Methylation of the MAP7 Gene

Zhao Y, Huang S, Tan X, et al. N6 -Methyladenosine-Modified CBX1 Regulates Nasopharyngeal Carcinoma Progression Through Heterochromatin Formation and STAT1 Activation. Adv Sci (Weinh). 2022;9(36):e2205091 [Article Link]

Methylation mAsterminds: Modified Histones and mRNA in NPC

Over the recent years, the role of histone and RNA modifications in tumor pathogenesis has been studied with increased interest. Zhao et al explore how the interplay between methylation of histones and RNA contributes to migration, invasion, and proliferation of nasopharyngeal carcinoma (NPC), a cancer known for its PD-1 inhibitor resistance upon distant metastasis. To test this hypothesis the group first sequenced NPC and normal nasopharyngeal epithelial tissues to determine differential RNA methylation of proteins involved in methylating histones between the conditions. The data showed that RNA of CBX1, a protein that participates in histone H3K9 methylation, is hypomethylated in NPC resulting in its transcript stabilization and subsequent increase in cellular abundance. After discovering that increased levels of hypomethylated CBX1 cause NPC proliferation, the next step was to determine the mechanism of CBX1’s oncogenicity. Based on the results of sequencing and immunoprecipitation assays in WT and CBX1 knockout NPC cells, Zhao et al found that CBX1 downregulates expression of MAP7 in NPC via promoting histone methylation and subsequent heterochromatin formation.  Understanding how the interplay of RNA and histone modifications contributes to differential expression of this relatively novel player in the cancer field brings us one step closer to understanding potential therapeutic functions of this protein.

Sofia V. Krylova’s Takeaway: This paper very convincingly demonstrates the crosstalk between post-transcriptional and epigenetic modifications in regulation of MAP7 expression. With this information, I am looking forward to future experiments of MAP7 function in cancer cells to further elucidate the mechanism of NPC tumorigenesis.