SETD7-mediated H3K4me1 activates ALDH1A3 to drive ferroptosis resistance in esophageal squamous cell carcinoma
Yang Feng, Xingyue Liu, Yangxia Wang, Mingyuan Zhang, Yangyang Ji, Longfeng Zhang, Yilu Tong, Fuyou Zhou, Hongyang Liu, Liang Ming, Junhu Wan
TL;DR
SETD7 boosts ESCC tumor growth and resistance to cell death by activating ALDH1A3 through epigenetic changes.
Contribution
Discovers a new epigenetic-metabolic pathway involving SETD7, H3K4me1, and ALDH1A3 in ESCC progression and ferroptosis resistance.
Findings
SETD7 is upregulated in ESCC and correlates with advanced clinical stages.
SETD7 promotes ESCC cell proliferation and migration while enhancing ferroptosis resistance.
SETD7 activates ALDH1A3 via H3K4me1 modification, increasing CoQ10H₂ and inhibiting lipid peroxidation.
Abstract
SET domain-containing 7 (SETD7, also known as KMT7 or SET7/9), a histone lysine methyltransferase (HKMT) responsible for catalyzing histone H3 lysine 4 monomethylation (H3K4me1), has emerged as a key regulator in multiple cancers. However, the biological functions and epigenetic regulatory mechanisms of SETD7 in esophageal squamous cell carcinoma (ESCC) remain unclear. Our study found that SETD7 expression is significantly upregulated in ESCC tissues and positively correlates with clinical staging. Functional analyses revealed that SETD7 promotes ESCC cell proliferation and migration in vitro, while accelerating tumor growth in vivo. Additionally, SETD7 knockdown increased ESCC cell sensitivity to ferroptosis induction, indicating its dual functionality in tumorigenesis and ferroptosis resistance. Cleavage Under Targets and Tagmentation (CUT&Tag) sequencing analysis systematically…
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Taxonomy
TopicsFerroptosis and cancer prognosis · Epigenetics and DNA Methylation · Immune cells in cancer