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

作者全名："Wu, Fan; He, Jin; Deng, Qianxi; Chen, Jun; Peng, Mingyu; Xiao, Jiayi; Zeng, Yiwei; Yi, Lin; Li, Zhuoqing; Tian, Rui; Jiang, Zheng"

作者地址："[Wu, Fan; He, Jin; Deng, Qianxi; Chen, Jun; Jiang, Zheng] Chongqing Med Univ, Affiliated Hosp 1, Dept Gastroenterol, Chongqing 400016, Peoples R China; [Peng, Mingyu] Chongqing Med Univ, Affiliated Hosp 1, Dept Resp & Crit Care Med, Chongqing 400016, Peoples R China; [Xiao, Jiayi] Sichuan Univ, West China Sch Med, 37 Guoxue Alley, Chengdu, Sichuan, Peoples R China; [Xiao, Jiayi] Sichuan Univ, West China Hosp, 37 Guoxue Alley, Chengdu, Sichuan, Peoples R China; [Zeng, Yiwei] China Med Univ, 77 Puhe Rd, Shenyang, Liaoning, Peoples R China; [Yi, Lin] Chongqing Med Univ, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China; [Li, Zhuoqing; Tian, Rui] Chongqing Univ Canc Hosp, Chongqing Key Lab Translat Res Canc Metastasis & I, Chongqing 400030, Peoples R China"

通信作者："Jiang, Z (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Gastroenterol, Chongqing 400016, Peoples R China."

来源：BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:000993910000001

JCR分区：Q3

影响因子：2.5

年份：2023

卷号：664

期号：　

开始页：108

结束页：116

文献类型：Article

关键词：Neuroglobin; Tumor suppressor; GNAI1; EGFR pathway; Pancreatic cancer

摘要："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."

基金机构：Natural Science Foundation of Chongqing [CSTC2021jscx-gksb-N0 023]; Medical and Industrial Integration project [22CDJyGRH-002]

基金资助正文：This study was funded by Natural Science Foundation of Chongqing (CSTC2021jscx-gksb-N0 023) and Medical and Industrial Integration project (22CDJyGRH-002).