Gastrin inhibits gastric cancer progression through activating the ERK-P65-miR23a/27a/24 axis

• Published in: Journal of experimental & clinical cancer research Vol. 37; no. 1; p. 115
• Main Authors: Zu, Li-Dong, Peng, Xing-Chun, Zeng, Zhi, Wang, Jing-Long, Meng, Li-Li, Shen, Wei-Wei, Hu, Chun-Ting, Yang, Ye, Fu, Guo-Hui
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 04.06.2018; BioMed Central; BMC
• Subjects: Analysis; Animals; Cancer therapies; Care and treatment; Cell Line, Tumor; Chemotherapy; Cisplatin - pharmacology; Complications and side effects; Development and progression; Disease Models, Animal; Disease Progression; Dosage and administration; Drug resistance; ERK; Extracellular Signal-Regulated MAP Kinases - metabolism; Female; Gastric cancer; Gastrin; Gastrins - metabolism; Gene Expression; Gene Expression Regulation, Neoplastic; Genes, Reporter; Genetic aspects; Heterografts; Hospitals; Humans; Kinases; Medical prognosis; Medicine; Mice; MicroRNA; MicroRNAs; MicroRNAs - genetics; miR23a/27a/24 cluster; Mutation; P65; Patients; Physiological aspects; Proteins; RNA Interference; Rodents; Signal Transduction; Stomach cancer; Stomach Neoplasms - genetics; Stomach Neoplasms - metabolism; Stomach Neoplasms - pathology; Surgery; Systematic review; Transcription Factor RelA - metabolism; Tumors; China; Gastric cancer; P65; Gastrin; ERK; miR23a/27a/24 cluster
• ISSN: 1756-9966; 0392-9078; 1756-9966
• DOI: 10.1186/s13046-018-0782-7

To test the hypothesis that activated extracellular signal-regulated kinase (ERK) regulates P65-miR23a/27a/24 axis in gastric cancer (GC) and the ERK-P65-miR23a/27a/24 axis plays an important role in the development of GC, and to evaluate the role of gastrin in GC progression and ERK-P65-miR23a/27a/24 axis. The component levels of the ERK-P65-miR23a/27a/24 axis in four fresh GC tissues, 101 paraffin-embedded GC tissues and four GC cell lines were determined by Western blotting, immunohistochemistry (IHC) or qRT-PCR. The effects of gastrin on GC were first evaluated by measuring gastrin serum levels in 30 healthy and 70 GC patients and performing a correlation analysis between gastrin levels and survival time in 27 GC patients after eight years of follow-up, then evaluated on GC cell lines, GC cell xenograft models, and patient-derived xenografts (PDX) mouse models. The roles of ERK-P65-miR23a/27a/24 axis in GC progression and in the effects of gastrin on GC were examined. ERK- P65-miR23a/27a/24 axis was proved to be present in GC cells. The levels of components of ERK-P65-miR23a/27a/24 axis were decreased in GC tissue samples and PGC cells. The decreased levels of components of ERK-P65-miR23a/27a/24 axis were associated with poor prognosis of GC, and ERK-P65-miR23a/27a/24 axis played a suppressive role in GC progression. Low blood gastrin was correlated with poor prognosis of the GC patients and decreased expression of p-ERK and p-P65 in GC tissues. Gastrin inhibited proliferation of poorly-differentiated GC (PGC) cells through activating the ERK-P65-miR23a/27a/24 axis. Gastrin inhibited GC growth and enhanced the suppression of GC by cisplatin in mice or PGC cell culture models through activating the ERK-P65-miR23a/27a/24 axis or its components. ERK-P65-miR23a/27a/24 axis is down-regulated, leading to excess GC growth and poor prognosis of GC. Low gastrin promoted excess GC growth and contributed to the poor prognosis of the GC patients by down-regulating ERK-P65-miR23a/27a/24 axis. Gastrin inhibits gastric cancer growth through activating the ERK-P65-miR23a/27a/24 axis.