The cell proliferation was determined by a CCK-8 assay (a), and the protein levels were determined using Western blotting (b). in GC progression and ERK-P65-miR23a/27a/24 axis. Methods 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 functions of ERK-P65-miR23a/27a/24 axis in GC progression and in the effects of gastrin on GC were examined. Results 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 Tos-PEG3-O-C1-CH3COO ERK-P65-miR23a/27a/24 axis. Gastrin inhibited GC growth and enhanced the suppression of GC by cisplatin Tos-PEG3-O-C1-CH3COO in mice or PGC cell culture models through activating the ERK-P65-miR23a/27a/24 axis or its components. Conclusions ERK-P65-miR23a/27a/24 axis is usually 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. Electronic supplementary material The online version of this article (10.1186/s13046-018-0782-7) contains supplementary material, which is available to authorized users. values were analyzed using GraphPad 5.0 software. *, comparison between the tumor and para-tumor tissues, value was calculated by a log-rank test. e Differential overall survival of GC patients with antrum (n?=?9) and other locations (value was calculated by a log-rank test. f, g The association between serum gastrin levels and p-ERK and p-P65 expression in GC tissues. The levels of p-ERK (f) and p-P65 (g) in GC tissue samples were decided using IHC. The representative images of 4 patients were showed. Rabbit Polyclonal to DBF4 Scale bar?=?50?m. p-ERK was expressed in 11 out of 13 patients with high serum gastrin, and in 12 out of 32 patients with low serum gastrin. p-P65 was expressed in 12 out of 13 patients with high serum gastrin, and in 12 out of 32 patients with low serum gastrin Gastrin inhibited proliferation of PGC cells through activating the ERK-P65-miR23a/27a/24 axis To further determine whether the ERK-P65-miR23a/27a/24 axis mediated suppression of PGC growth by gastrin, we next treated SGC7901 cells with gastrin and decided p-ERK and p-P65 levels using Western blotting, and miR-23a, miR-27a, and miR-24 levels using qRT-PCR. The results showed that p-ERK and p-P65 levels (Fig.?6a) and miR-23a, miR-27a, and miR-24 levels (Fig. ?(Fig.6b)6b) were increased, and proliferation of SGC7901 cells and Cyclin D1 expression were inhibited (Fig. ?(Fig.6c)6c) in SGC7901 cells after gastrin treatment. There was a good pairing between these three miRNAs and cyclin D1 3 UTR (Fig. ?(Fig.6d).6d). The miR-23a, miR-24 and miR-27a mimics suppressed luciferase activity ofCCND1 3-UTR Tos-PEG3-O-C1-CH3COO reporter gene after cotransfection into HEK293T cells (Fig. ?(Fig.6e).6e). We also.
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