Oncosuppressive role of MicroRNA-205-3p in gastric cancer through inhibition of proliferation and induction of senescence Oncosuppressive role of MicroRNA-205 in gastric cancer

Background: Our previous study showed that CXCL11 could play an immunomodulatory role. In this study, we investigated the regulator (miR-205-3p) of CXCL11 and the mechanism of miR-205-3p as a tumor suppressor gene in gastric cancer (GC). Materials and methods: A target relationship between miR-205-3p and CXCL11 was revealed by using the bioinformatics method. This study detected the expressions of miR-205-3p and CXCL11 through qRT-PCR and Western blotting. Moreover, the expressions of Akt, PD-L1, p16, p21, and senescence-associated secretory phenotype (SASP) factor were determined. The effects of miR-205 on proliferation, invasion, and senescence of GC cells were assessed by using methods, such as transfection, Transwell assay, tablet cloning, flow cytometry, and senescence-associated beta-galactosidase (SA-8-gal) staining. Furthermore, the effects were verified using methods, like immunohistochemistry, flow cytometry and SA-8-gal in animal experiments. Results: Based on the study, it is found that the expression of miR-205-3p is down-regulated, while that of CXCL11 is up-regulated in GC cell lines. By regulating CXCL11, miR-205-3p inhibits Akt activation, reduces the proliferation and invasion of GC cells, promotes cell apoptosis, induces senescence of GC cells, and secretes immunostimulatory SASP factor. The animal experiments confirm that miR-205-3p promotes cell senescence, down-regulates the immunosuppressive signal induced by PD-L1, and promotes secretion of immunostimulatory SASP factor, so that more T cells are recruited in blood and tumors. Conclusions: This study revealed the molecular mechanism of miR-205-3p in inhibiting proliferation and invasion and inducing senescence of GC cells by regulating CXCL11 and Akt pathways in animal and cell experiments.

Automated summary

The study reveals that miR-205-3p is down-regulated while CXCL11 is up-regulated in gastric cancer cell lines. By regulating CXCL11, miR-205-3p inhibits Akt activation, reduces proliferation and invasion of GC cells, promotes apoptosis, induces cell senescence, and secretes immunostimulatory SASP factor. Animal experiments confirm that miR-205-3p promotes cell senescence, down-regulates the immunosuppressive signal induced by PD-L1, and recruits more T cells in blood and tumors.