MicroRNA-559 restrains gastric cancer progression via activating AKT signaling pathway by targeting TRIM14

Abstract Background: MicroRNAs (miRNAs) act as pivotal functions in gastric cancer (GC) carcinogenesis and progression. MiR-559 has been defined as a potential cancer suppressor gene in a few cancers. Nevertheless, the biological effect of miR-559 in human GC and the underlying molecular mechanism still unclear and need to be further illuminated. Methods: Quantitative real-time PCR (qRT-PCR) was fulfilled for measuring the miR-559 expression level in GC. The dual-luciferase reporter was used to verify that tripartite motif-containing 14 (TRIM14) is a target gene of miR-559. The expression levels of TRIM14 were examined by qRT-PCR and Western blot in GC tissue specimens and cell lines. The effects of miR-559 on GC cell growth were detected with MTT and cell counting assays. Cell cycle and apoptosis were examined by using flow cytometry. Overexpression and siRNA further demonstrated the role of TRIM14 in GC. Results: Our results revealed that miR-559 expression was dramatically downregulated in human GC tissue specimens and cell lines. MiR-559 overexpression restrained GC cell growth, and induced cell cycle G1-S phase arrest and apoptosis. MiR-559 inhibitors promoted cell multiplication and cell cycle G1-S transition, and inhibited apoptosis. MiR-559 level was negatively related to TRIM14 mRNA level in GC. The results showed that TRIM14 was affirmed to be a target gene of miR-559. MiR-559 overexpression downregulated the TRIM14 expression, and miR-559 inhibitors upregulated the TRIM14 expression. Particularly, knockdown of TRIM14 gave rise to the semblable cellular effects observed upon miR-559 overexpression. TRIM14 overexpression recapitulated the revulsive cellular and molecular effects by suppression of miR-559. Furthermore, both miR-559 overexpression and TRIM14 silencing led to the inhibition of the AKT signaling pathway. On the contrary, miR-559 suppression and TRIM14 overexpression activated the AKT signaling pathway, and inhibited Bax/Bcl-2 pathway. Conclusions: The findings illustrate that miR-559 restrains cell multiplication via suppressing the AKT signaling pathway in human GC and induces cell apoptosis through the suppression of Bax/Bcl-2 signaling pathway via targeting TRIM14. The findings imply that miR-559 acts as a pivotal function in human GC and represents a latent novel target in GC therapy.