miR-135a suppresses migration of gastric cancer cells by targeting TRAF5-mediated NF-κB activation.

Background: As crucial regulators and possible biomarkers for cancer development, miRNAs have attracted intensive attention during the last two decades. Among the known miRNAs, miR-135a has been indicated as a tumor suppressor in several cancer types, whereas its roles and mechanisms in gastric cancer (GC) remain largely unclear.

Materials and methods: Quantitative PCR (qPCR) was conducted to detect the expression of miR-135a in paired GC tissues as well as cell lines. The prognostic value was evaluated by Kaplan-Meier survival analysis. Wound healing and transwell assays were performed to determine the roles of miR-135a in GC cell migration. Dual-luciferase reporter assay, qPCR, and Western blot analysis were used to validate the targeting of TRAF5 and subsequent NF-κB pathway by miR-135a. Rescue experiments were done to explain the involvement of TRAF5 in mediating the anti-migration effect of miR-135a in GC cells. Finally, the expression of TRAF5 was examined in paired GC tissues.

Results: miR-135a was confirmed to be decreased in GC tissues and cell lines, and its lower expression predicted worse overall survival. Cellular experiments proved that miR-135a suppressed migration in GC cells. Through directly targeting TRAF5 and subsequently inhibiting NF-κB pathway, miR-135a might efficiently inhibit GC cell metastasis. Furthermore, we found that TRAF5 overexpression was negatively correlated with miR-135a expression in GC tissues.

Conclusion: Our study indicated that miR-135a serves a suppressing role in GC cell migration by targeting TRAF5 and the downstream NF-κB pathway.