LncRNA A2M-AS1 promotes ferroptosis in pancreatic cancer via interacting with PCBP3.
LncRNA A2M-AS1 promotes ferroptosis in pancreatic cancer via interacting with PCBP3.
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DOI：
10.1158/1541-7786.mcr-22-0024
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发表时间：
2022-08
期刊：
影响因子：
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通讯作者：
X. Qiu;Qiuyue Shi;Xianglian Zhang;Xiaoyan Shi;Haixing Jiang;Shanyu Qin
中科院分区：
文献类型：
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作者：
X. Qiu;Qiuyue Shi;Xianglian Zhang;Xiaoyan Shi;Haixing Jiang;Shanyu Qin
铁凋亡是一种新发现的细胞死亡机制，与多种肿瘤的发生、发展密切相关，非编码RNA（ncRNA）在其中的作用研究相对较少。本研究确定了最近研究的长链非编码RNA（lncRNA）A2 M-AS 1在胰腺癌（PC）中的低水平，并表明其与PC患者的总生存时间呈正相关。A2 M-AS 1主要定位于细胞浆，抑制PC细胞的增殖、迁移、侵袭和肿瘤生长。此外，Erastin诱导的铁凋亡增加A2 M-AS 1的表达水平。A2 M-AS 1的过表达促进PC中的铁凋亡，而A2 M-AS 1的沉默抑制了铁凋亡。A2 M-AS 1可直接与铁代谢过程中起重要作用的多聚腺苷酸结合蛋白3（PCBP 3）相互作用，从而促进PC的铁凋亡。此外，A2 M-AS 1/PCBP 3轴可促进p38的激活，抑制AKT-mTOR信号通路的磷酸化，参与调节铁凋亡。因此，以A2 M-AS 1/PCBP 3轴为靶点调控铁凋亡可能为未来PC的治疗提供新的靶点。结论：A2 M-AS 1可能成为治疗PC的新靶点。
Ferroptosis is a newly-discovered cell death mechanism involved in the progression of various tumors, the role of non-coding RNAs (ncRNAs) in it was relatively less explored. This study identified the low levels of a recently studied long non-coding RNA (lncRNA), A2M-AS1, in pancreatic cancer (PC) and suggested its positive correlation with the overall survival time of PC patients. A2M-AS1 was mainly localized in the cytoplasm, inhibiting the cellular proliferation, migration, and invasion as well as the tumor growth of the PC cells. Moreover, the Erastin-induced ferroptosis increased the expression levels of A2M-AS1. The overexpression of A2M-AS1 promoted ferroptosis in the PC, 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 PC. 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 PC in the future. Implications: A2M-AS1 might be a potential novel therapeutic target for PC patients in the future.