MiR-429 Induces Gastric Carcinoma Cell Apoptosis Through BcI-2

Background/Aims: MicroRNAs (miRNAs) play an essential role in the tumorigenesis of gastric carcinoma (GC). MiR-429 has been recently reported to inhibit GC growth, but the underlying mechanisms are not clear. Methods: Here, we studied the levels of miR-429 and anti-apoptotic protein BcI-2 in GC specimens. We performed bioinformatics analyses and used luciferasereporter assay to analyze the relationship between miR-429 and BcI-2 in GC cells. Cell survival upon Fluorouracil treatment was analyzed in a CCK assay. Cell apoptosis was measured by flow cytometry based FITC Annexin V apoptosis detection assay. Results: MiR-429 levels were significantly decreased and BcI-2 levels were significantly increased in GC specimens, compared to the paired adjacent non tumor gastric tissue. Moreover, the levels of miR-429 and BcI-2 inversely correlated in GC specimens. MiR-429-low subjects had an overall inferior survival, compared to miR-429-high subjects. Bioinformatics analyses showed that miR-429 targeted the 3'-UTR of BcI-2 mRNA to inhibit its translation, which was confirmed by luciferase-reporter assay. Overexpression of miR-429 inhibited BcI-2-mediated cell survival against apoptosis induced by Fluorouracil, while depletion of miR-429 augmented it. Conclusion: Our data suggest that miR-429 suppression in GC promotes BcI-2-mediated cancer cell survival against chemotherapy-induced cell death. Re-expression of miR-429 levels in GC cells may enhance cancer apoptosis during chemotherapy. (C) 2015 The Author(s) Published by S. Karger AG, Basel