Objective To investigate the expression and clinical pathological significance of PIWI-interacting RNA-47851 (piR-47851) in gastric adenocarcinoma and its influence on proliferation.

Methods The expression of piR-47851 was detected in 79 gastric adenocarcinoma tissues by real time fluorescence quantitative polymerase chain reaction (qRT-PCR), and the correlation of piR-47851 expression level and clinical features with survival and prognosis were analyzed. The effect of piR-47851 on proliferation activity of gastric cancer cells was observed by cell proliferation experiments. Informatics websites were used to predict the downstream target genes of piR-47851. The wild-type and mutant plasmids for the 3'untranslated region (UTR) of MAPK1 gene were established, and a dual luciferase reporting system was used to verify that piR-47851 binded to the 3'UTR of MAPK1 gene, thereby inhibiting MAPK1 protein synthesis. The effect of overexpression/silencing of piR-47851 on MAPK1 expression level was examined through qRT-PCR experiment. Rescue experiment was used to confirm the direct regulatory effect of piR-47851 on MAPK1 and explore the effect of piR-47851/MAPK1 on the proliferation of gastric cancer cells. The effect of reduced piR-47851 expression on the volume and weight of transplanted tumors was observed in nude mice by xenograft tumor experiments; the effect of reduced piR-47851 expression on the cell proliferation activity of xenograft tumors was observed by Ki-67 staining.

Results The qRT-PCR experiment result showed that the expression level of piR-47851 in 79 gastric adenocarcinoma tissues was significantly higher than that in normal gastric tissues adjacent to the cancer (P < 0.05). The expression level of piR-47851 was significantly correlated with tumor size, degree of differentiation, and survival prognosis (P < 0.05). Bioinformatics suggested that there was a complementary binding site between piR-47851 and MAPK1 gene 3'UTR. The dual luciferase reporter gene experiment showed that piR-47851 was able to significantly inhibit fluorescence enzyme activity in the MAPK1 wild-type transfection group, while this inhibitory effect was not observed in the MAPK1 mutant group. The CCK-8 proliferation activity experiment showed that overexpression of piR-47851 was able to significantly increase the proliferation activity of gastric cancer cells; after reducing piR-47851, the proliferation activity of cells decreased significantly (P < 0.05). Rescue experiment indicated that after changing the expression of piR-47851 and (or) MAPK1 and then detecting the expression level of MAPK1 by qRT-PCR, the MAPK1 could be regulated by piR-47851. Overexpression of MAPK1 could functionally reduce the proliferation promoting effect of piR-47851 on gastric cancer cells, while reducing MAPK1 expression could further enhance the proliferation activity of gastric cancer cells. In xenograft tumor experiments, reducing the expression of piR-47851 significantly resulted in smaller tumor growth volume and weight (P < 0.05). The proliferation index Ki-67 staining showed that the number of proliferative active cells in the reduced piR-47851 expression group was significantly lower than that in the control group (P < 0.05), which further validated the promotional effect of piR-47851 on cell proliferation.

Conclusion The expression level of piR-47851 is increased in gastric adenocarcinoma tissues, which is closely related with tumor size and survival prognosis. The piR-47851 downregulates MAPK1 protein expression by binding to the 3'UTR of MAPK1, thereby promoting the proliferation of gastric cancer cells.