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. 2024 Sep 15;38(17):e70028.
doi: 10.1096/fj.202401151R.

Circ_0005397 inhibits ferroptosis of pancreatic cancer cells by up-regulating PCBP2 through KAT6A/H3K9Ac

Tengfei Qu  1   2 , Lichao Cha  1   2 , Hongliang Liu  3 , Lantian Tian  1   2 , Xiao Hu  1 , Hao Zou  1 , Yujie Feng  1 , Chuandong Sun  1 , Jingyu Cao  1 , Weidong Guo  1   2 , Fabo Qiu  1   2 , Bin Zhou  1   2
Affiliations

Circ_0005397 inhibits ferroptosis of pancreatic cancer cells by up-regulating PCBP2 through KAT6A/H3K9Ac

Tengfei Qu et al. FASEB J. .

Abstract

Pancreatic cancer is a highly aggressive and lethal carcinoma. Circular RNAs (circRNAs) serve key regulatory functions in pancreatic cancer. Ferroptosis was induced by erastin treatment and analyzed by examining malondialdehyde (MDA), iron, Fe2+ and glutathione (GSH). C11-BODIPY 581/591 was used to stain cells for analyzing lipid peroxidation. RNA immunoprecipitation, pull-down and chromatin immunoprecipitation assays were applied to evaluate intermolecular interaction. Mice received subcutaneous injection of pancreatic cancer cells as a model of subcutaneous tumor for in vivo tests. Circ_0005397 was abundantly expressed in pancreatic cancer, and its upregulation was associated with low survival of patients with pancreatic cancer. Circ_0005397 expression was induced by EIF4A3. PCBP2 was highly expressed in pancreatic cancer, and circ_0005397 and PCBP2 were positively correlated in patients with pancreatic cancer. Circ_0005397 knockdown sensitized pancreatic carcinoma cells to ferroptosis via downregulating PCBP2. Circ_0005397 promoted PCBP2 transcription via facilitating the binding of KAT6A and H3K9ac to PCBP2 promoter. Silencing of circ_0005397 reduced tumor growth by enhancing erastin-induced ferroptosis in vivo. EIF4A3-induced circ_0005397 inhibited erastin-induced ferroptosis in pancreatic cancer by promoting PCBP2 expression through KAT6A and H3K9ac.

Keywords: Circ_0005397; EIF4A3; H3K9ac; KAT6A; ferroptosis; pancreatic cancer.

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References

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