LncRNA A2M-AS1 Promotes Ferroptosis in Pancreatic Cancer via Interacting With PCBP3

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 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 cyto-plasm, inhibiting the cellular proliferation, migration, and invasion as well as the tumor growth of the pancreatic cancer cells. More -over, 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 promot-ing the ferroptosis in pancreatic cancer. In addition, the A2M-AS1/ PCBP3 axis could facilitate the p38 activation and inhibit the phos-phorylation of the AKT-mTORsignalingpathway; 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.

Automated summary

A2M-AS1 expression correlates positively with overall survival time in pancreatic cancer patients, promoting ferroptosis when overexpressed and inhibiting it when silenced. It interacts with PCBP3 to regulate iron metabolism in pancreatic cancer.