基因沉默
胰腺癌
癌症研究
蛋白激酶B
长非编码RNA
癌症
生物
核糖核酸
PI3K/AKT/mTOR通路
信号转导
癌细胞
细胞生物学
基因
遗传学
作者
Xin Qiu,Qiuyue Shi,Xiang-lian Zhang,Hong He,Hai-Xing Jiang,Shanyu Qin
标识
DOI:10.1158/1541-7786.mcr-22-0024
摘要
Abstract Ferroptosis is a newly-discovered cell death mechanism involved in the progression of various tumors, the role of noncoding RNAs (ncRNAs) in it was relatively less explored. This study identified the low levels of a recently studied long noncoding RNA (lncRNA), A2M-AS1, in pancreatic cancer and suggested its positive correlation with the overall survival time of patients with pancreatic cancer. A2M-AS1 was mainly localized in the cytoplasm, inhibiting the cellular proliferation, migration, and invasion as well as the tumor growth of the pancreatic cancer cells. Moreover, the Erastin-induced ferroptosis increased the expression levels of A2M-AS1. The overexpression of A2M-AS1 promoted ferroptosis in the pancreatic cancer, which was inhibited by the silencing of A2M-AS1. Mechanically, A2M-AS1 could directly interact with the poly (rC) binding protein 3 (PCBP3), which plays an important role in the process of iron metabolism, thereby promoting the ferroptosis in pancreatic cancer. In addition, the A2M-AS1/PCBP3 axis could facilitate the p38 activation and inhibit the phosphorylation of the AKT–mTOR signaling pathway; all these participate in regulating ferroptosis. In conclusion, the regulation of ferroptosis by targeting the A2M-AS1/PCBP3 axis might provide a novel target for the treatment of pancreatic cancer in the future. Implications: A2M-AS1 might be a potential novel therapeutic target for patients with pancreatic cancer in the future.
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