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.
Keywords: miR-135a, gastric cancer, TRAF5, NF-κB pathway, cell migration