LncRNA ABHD11-AS1在Erastin诱导的胰腺癌细胞铁死亡中的作用及其机制

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Abstract ［Abstract］Objective： To investigate the role of long non-coding RNA (lncRNA) α/β-hydrolase domain containing protein 11-antisense strand 1 (ABHD11-AS1) in Erastin-induced ferroptosis of pancreatic cancer cells and its potential mechanism. Methods： The expression of ABHD11-AS1 and prognosis of patients in pancreatic cancer were analyzed by GEPIA platform. qRT-PCR was used to detect ABHD11-AS1 expression in human pancreatic cancer cells PANC1, MIApaca2 and PaTu8988, and CCK8 assay was used to calculate the IC50 of Erastin. PANC1 cells was transfected with pcDNA3.1 or PCDNA3.1-ABHD11-AS1 plasmid to overexpress ABHD11-AS1. PaTu8988 cells was transfected with siControl, siRNA1 and siRNA2 to interfere ABHD11-AS1; and the transfection efficiency was detected by qRT-PCR. The cells were treated with control (0 μmol/L Erastin), Erastin (IC50 concentration), respectively; and cell viability was detected by CCK8 assay. The content of malondialdehyde (MDA) and glutathione (GSH) were determined by ELISA. In addition, in pcDNA3.1ABHD11-AS1 and siRNA1 groups, Erastin was added and ferroptosis inhibiting agent Ferrostatin-1, necrosis salvage agent Necrosstatin-1 or apoptosis inhibitor ZVADFMK were added at the same time, and cell viability was detected by CCK8 assay. Western blotting was used to detect the protein expression of glutathione peroxidase 4 (GPX4), mammalian target of rapamycin (mTOR), and phosphorylated mTOR (p-mTOR) in pancreatic cancer cells of 5 groups. Results： The expression level of ABHD11-AS1 in pancreatic cancer tissues was significantly higher than that in adjacent tissues, and the prognosis of patients with higher expression of ABHD11-AS1 was poorer (P<0.05). The expression level of ABHD11-AS1 from low to high in human pancreatic cancer cells were PANC1, MIApaca-2, and PaTu8988. The trend of Erasin IC50 was the same as that of ABHD11-AS1, which was 2.245, 11.760, 17.120 μmol/L, respectively. Compared with the pcDNA3.1 group, PCDNA3.1ABHD11AS1 group showed higher levels of cell viability and GSH content, while lower content of MDA (all P<0.05). Compared with the siControl group, the cell viability and GSH content in siRNA1 group and siRNA2 group decreased significantly, and the MDA content increased significantly (P<0.05). Only Ferrostatin-1 could rescue the cell viability of pcDNA3.1ABHD11-AS1 and siRNA1 groups (P<0.05). ABHD11-AS1 increased cell viability under Erastin treatment by enhancing ferroptosis resistance. Overexpression of ABHD11-AS1 could promote the activation of mTOR and enhance the expression of GPX4 (P<0.05); knockdown of ABHD11-AS1 produced the opposite effect. Conclusion： LncRNA ABHD11-AS1 could promote the expression of GPX4 by activating mTOR1, thus promoting ferroptosis resistance of pancreatic cancer cells.

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Received: 24 February 2022

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http://zzs.ujs.edu.cn/xbyxb/EN/ OR http://zzs.ujs.edu.cn/xbyxb/EN/Y2023/V33/I01/1

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