Neuroglobin inhibits pancreatic cancer proliferation and metastasis by targeting the GNAI1/EGFR/AKT/ERK signaling axis

Pancreatic cancer is an extremely aggressive malignancy with a very disappointing prognosis. Neuro-globin (NGB), a member of the globin family, has been demonstrated to have a significant role in a variety of tumor forms. The possible role of NGB as a tumor suppressor gene in pancreatic cancer was inves-tigated in this work. Information from the public dataset TCGA combined with GTEx was used to analyze the finding that NGB was commonly downregulated in pancreatic cancer cell lines and tissues, corre-lating with patient age and prognosis. The expression of NGB in pancreatic cancer was investigated via RT-PCR, qRT-PCR, and Western blot experiments. In-vitro and in-vivo assays, NGB elicited cell cycle arrest in the S phase and apoptosis, hindered migration and invasion, reversed the EMT process, and sup-pressed cell proliferation and development. The mechanism of action of NGB was predicted via bioin-formatics analysis and validated using Western blot and co-IP experiments revealed that NGB inhibited the EGFR/AKT/ERK pathway by binding to and reducing expression of GNAI1 and p-EGFR. In addition, pancreatic cancer cells overexpressing NGB showed increased drug sensitivity to gefitinib (EGFR-TKI). In conclusion, NGB inhibits pancreatic cancer progression by specifically targeting the GNAI1/EGFR/AKT/ ERK signaling axis.(c) 2023 Elsevier Inc. All rights reserved.

Automated summary

This study investigates the role of neuro-globin (NGB) as a tumor suppressor gene in pancreatic cancer. Analysis of the TCGA and GTEx public datasets reveals that NGB expression is commonly downregulated in pancreatic cancer cells and tissues, and this correlates with patient age and prognosis. Experimental results show that NGB inhibits pancreatic cancer progression by inducing cell cycle arrest, apoptosis, inhibiting migration and invasion, reversing the EMT process, and suppressing cell proliferation and development. Further analysis and experiments confirm that NGB inhibits the EGFR/AKT/ERK pathway by binding to and reducing the expression of GNAI1 and p-EGFR.