Department of Hepatobiliary and Pancreatic Surgery, the Affiliated Hospital of Qingdao University, Qingdao, China.
Department of Retroperitoneal Tumor Surgery, the Affiliated Hospital of Qingdao University, Qingdao, China.
FASEB J. 2024 Sep 15;38(17):e70028. doi: 10.1096/fj.202401151R.
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, Fe 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.
胰腺癌是一种高度侵袭性和致命性的癌。环状 RNA（circRNA）在胰腺癌中发挥关键的调节作用。通过检测丙二醛（MDA）、铁、Fe 和谷胱甘肽（GSH）来诱导铁死亡。使用 C11-BODIPY 581/591 染色细胞来分析脂质过氧化。应用 RNA 免疫沉淀、下拉和染色质免疫沉淀测定来评估分子间相互作用。通过皮下注射胰腺癌细胞建立皮下肿瘤模型来进行体内实验。Circ_0005397 在胰腺癌中大量表达，其上调与胰腺癌患者的低生存率相关。Circ_0005397 的表达受 EIF4A3 诱导。PCBP2 在胰腺癌中高表达，并且在胰腺癌患者中 Circ_0005397 和 PCBP2 呈正相关。Circ_0005397 敲低通过下调 PCBP2 使胰腺癌细胞对铁死亡敏感。Circ_0005397 通过促进 KAT6A 和 H3K9ac 与 PCBP2 启动子结合来促进 PCBP2 转录。沉默 Circ_0005397 通过增强依维莫司诱导的铁死亡来减少体内肿瘤生长。EIF4A3 诱导的 Circ_0005397 通过 KAT6A 和 H3K9ac 促进 PCBP2 表达来抑制依维莫司诱导的铁死亡。
