Functional variation of SLC52A3 rs13042395 predicts survival of Chinese gastric cancer patients.

Abstract

The solute carrier family 52 member 3 (SLC52A3) gene encodes riboflavin transporter protein which is essential to maintain mitochondrial function in cells. In our research, we found that SLC52A3 rs13042395 C > T variation was significantly associated with poor survival in a 926 Chinese gastric cancer (GCa) patients cohort (CC/CT genotype versus TT genotype, HR = 0.57, 95%CI (0.40-0.82), log-rank P = 0.015). The SLC52A3 rs13042395 C > T change led to its increased mRNA expression according to expression quantitative trait loci analysis (P = 0.0029). In vitro, it was revealed that rs13042395 C allele had higher binding affinity to inhibitory transcription factor Meis homeobox 1 (MEIS1) compared with T allele, knock-down of MEIS1 could up-regulate SLC52A3, and overexpression of SLC52A3 contributed to the increased ability of proliferation, colony formation, migration and invasion in GCa cells. Subsequently, the bioinformatics analysis combined with experiments in vitro suggested that Gap junction protein alpha 1 (GJA1) was the downstream effector of SLC52A3, SLC52A3 may promote the GCa cells aggressiveness by down-regulating the GJA1 expression. Overall, SLC52A3 genetic variant rs13042395 C > T change was associated with poorer survival in Chinese GCa patients and increased SLC52A3 expression by interaction with MEIS1. SLC52A3 promoted the GCa cells aggressiveness by down-regulating the GJA1 expression.