Melatonin Suppresses Colorectal Cancer Alongside Coordinated Changes in H3K4me3Q5ser and m⁶A Modifications.

Authors

Wanlu Zhang, Lin Yuan, Dawei Yu, Shihong Qi, Chang Liu, Dongxu Wang, Wenna Wang, Yi Zhang, Sihui Zhang, Liting Lu, Min Wu, Yongye Huang

Published in

Journal of pineal research. Volume 78. Issue 6. Pages e70192.

Abstract

Melatonin has demonstrated antitumor activity in various cancer models, but its effects may depend on the therapeutic dose and cellular environment. We found that melatonin at millimolar concentrations significantly downregulated transglutaminase 2 (TGM2), histone serotonylation (H3K4me3Q5ser), and YTHDF1/m⁶A (N6-methyladenosine) in a colorectal cancer model. Cross-interference between TGM2 and YTHDF1 supports a link between these regulatory processes, while molecular docking, pharmacological interventions, and co-immunoprecipitation experiments suggest the existence of a signaling pathway involving melatonin and the HTR2B receptor. A combined analysis of CHIP-seq and meRIP-seq identified salt-induced kinase 1 (SIK1) as a potential downstream target, and SIK1 interference affected the proliferation and migration of colorectal cancer. Collectively, these findings support a working model in which melatonin-induced tumor suppression is associated with coordinated changes in TGM2/H3K4me3Q5ser and YTHDF1-associated m⁶A regulation, with SIK1 emerging as a potential convergent downstream effector.

PMID:
42864905
Bibliographic data and abstract were imported from PubMed on 13 Oct 2026.

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