Functional variation of SLC52A3 rs13042395 predicts survival of Chinese gastric cancer patients.
Functional variation of SLC52A3 rs13042395 predicts survival of Chinese gastric cancer patients.
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SLC52A3 rs13042395的功能变异预测中国胃癌患者的生存
DOI：
10.1111/jcmm.15798
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发表时间：
2020-11
影响因子：
5.3
通讯作者：
Guo W
中科院分区：
文献类型：
--
作者：
Qu X;Cheng L;Zhao L;Qiu L;Guo W
溶质载体家族52成员3 （SLC52A3）基因编码核黄素转运蛋白，该蛋白对维持细胞线粒体功能至关重要。在我们的研究中，我们发现SLC52A3 rs13042395 C > T变异与926例中国胃癌（GCa）患者的不良生存率显著相关（CC/CT基因型与TT基因型，HR = 0.57, 95%CI(0.40‐0.82),log‐rank P = 0.015）。表达数量性状位点分析显示，SLC52A3 rs13042395 C > T的改变导致其mRNA表达量增加（P = 0.0029）。体外研究发现，与T等位基因相比，rs13042395 C等位基因对抑制转录因子Meis同源盒1 （MEIS1）具有更高的结合亲和力，MEIS1的敲低可以上调SLC52A3， SLC52A3的过表达有助于提高GCa细胞的增殖、集落形成、迁移和侵袭能力。随后，生物信息学分析结合体外实验表明，缝隙连接蛋白α 1 （GJA1）是SLC52A3的下游效应蛋白，SLC52A3可能通过下调GJA1的表达来促进GCa细胞的侵袭性。总体而言，SLC52A3基因变异rs13042395 C b> T的改变与中国GCa患者较差的生存率相关，并且通过与MEIS1的相互作用增加了SLC52A3的表达。SLC52A3通过下调GJA1的表达来促进GCa细胞的侵袭性。
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.
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DOI：
10.1093/brain/awx231
发表时间：
2017-11-01
期刊：
Brain : a journal of neurology
影响因子：
--
作者：
Manole A;Jaunmuktane Z;Hargreaves I;Ludtmann MHR;Salpietro V;Bello OD;Pope S;Pandraud A;Horga A;Scalco RS;Li A;Ashokkumar B;Lourenço CM;Heales S;Horvath R;Chinnery PF;Toro C;Singleton AB;Jacques TS;Abramov AY;Muntoni F;Hanna MG;Reilly MM;Revesz T;Kullmann DM;Jepson JEC;Houlden H
通讯作者：
Houlden H
间隙连接和癌症：沟通50年。
DOI：
10.1038/nrc.2016.105
发表时间：
2016-12
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Aasen T;Mesnil M;Naus CC;Lampe PD;Laird DW
通讯作者：
Laird DW
SLC52A3 表达由 NF-kappa B p65/Rel-B 激活，可作为食管癌的预后生物标志物
DOI：
10.1007/s00018-018-2757-4
发表时间：
2018-07
期刊：
Cellular and molecular life sciences : CMLS
影响因子：
--
作者：
Long L;Pang XX;Lei F;Zhang JS;Wang W;Liao LD;Xu XE;He JZ;Wu JY;Wu ZY;Wang LD;Lin DC;Li EM;Xu LY
通讯作者：
Xu LY
影响因子：
2.6
作者：
Wei, W.;Ji, A.;Wang, L. D.
通讯作者：
Wang, L. D.
影响因子：
3.5
作者：
Liu, Dan;Zhou, Hongfeng;Zhang, Xufeng
通讯作者：
Zhang, Xufeng