HNRNPK inhibits gastric cancer cell proliferation through p53/p21/CCND1 pathway.
HNRNPK inhibits gastric cancer cell proliferation through p53/p21/CCND1 pathway.
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HNRNPK通过p53/p21/CCND1通路抑制胃癌细胞增殖
DOI：
10.18632/oncotarget.21873
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发表时间：
2017-11-28
期刊：
影响因子：
--
通讯作者：
Gao R
中科院分区：
文献类型：
--
作者：
Huang H;Han Y;Yang X;Li M;Zhu R;Hu J;Zhang X;Wei R;Li K;Gao R
胃癌是人类最常见的恶性肿瘤之一。胃癌发生和发展的分子机制仍不清楚。在本研究中，我们发现，异质核核糖核蛋白K（HNRNPK）是一个有效的预后指标，特别是在早期胃癌患者。HNRNPK过表达可以通过p53/p21/CCND 1轴抑制体外肿瘤细胞增殖和集落形成，并抑制体内肿瘤生长。生物信息学分析表明，HNRNPK相关基因在细胞周期和DNA复制过程中富集。蛋白质相互作用网络显示HNRNPK与p53、p21等肿瘤相关基因存在物理相互作用。GSEA结果显示，HNRNPK表达与辐射反应和DNA修复呈正相关，与血管生成、TGF-β和Hedgehog通路激活呈负相关。最后，包括甘氨酸在内的几种化学物质可能通过上调HNRNPK来抑制GC进展。我们的研究表明，HNRNPK可能在胃癌中发挥抑癌作用，并可能成为胃癌治疗的潜在靶点。
Gastric cancer (GC) is one of the most common human cancers. The molecular mechanisms underlying GC carcinogenesis and progression are still not well understood. In this study, we showed that heterogeneous nuclear ribonucleoprotein K (HNRNPK) was an effective prognostic marker for GC patients especially in early stage. Overexpression of HNRNPK can retard tumor cell proliferation and colony formation in vitro and inhibit tumor growth in vivo through p53/p21/CCND1 axis. Bioinformatics analyses indicated that HNRNPK associated genes were enriched in cell cycle and DNA replication process. Protein-protein interaction network showed that HNRNPK was physically interacted with p53, p21 and other cancer related genes. Besides, GSEA showed that HNRNPK expression was positively correlated with GAMMA radiation response and DNA repair, while negatively correlated with angiogenesis, TGF-β and Hedgehog pathway activation. Finally, several chemicals including Glycine that may repress GC progression through upregulating HNRNPK are suggested. Our study demonstrated that HNRNPK may play as a tumor suppressor in gastric cancer and could be a potential therapeutic target for GC.
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DOI：
10.1083/jcb.201009059
发表时间：
2011-01-24
期刊：
The Journal of cell biology
影响因子：
--
作者：
Muller PA;Vousden KH;Norman JC
通讯作者：
Norman JC
影响因子：
20.3
作者：
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通讯作者：
Doehner, Konstanze
影响因子：
50.3
作者：
Gallardo M;Lee HJ;Zhang X;Bueso-Ramos C;Pageon LR;McArthur M;Multani A;Nazha A;Manshouri T;Parker-Thornburg J;Rapado I;Quintas-Cardama A;Kornblau SM;Martinez-Lopez J;Post SM
通讯作者：
Post SM
DOI：
10.1073/pnas.0607595104
发表时间：
2007-05-22
影响因子：
11.1
作者：
Inoue, Atsushi;Sawata, Shinya Y.;Wadhwa, Renu
通讯作者：
Wadhwa, Renu
DOI：
10.1056/nejmoa1301689
发表时间：
2013-05-30
期刊：
The New England journal of medicine
影响因子：
--
作者：
Cancer Genome Atlas Research Network;Ley TJ;Miller C;Ding L;Raphael BJ;Mungall AJ;Robertson A;Hoadley K;Triche TJ Jr;Laird PW;Baty JD;Fulton LL;Fulton R;Heath SE;Kalicki-Veizer J;Kandoth C;Klco JM;Koboldt DC;Kanchi KL;Kulkarni S;Lamprecht TL;Larson DE;Lin L;Lu C;McLellan MD;McMichael JF;Payton J;Schmidt H;Spencer DH;Tomasson MH;Wallis JW;Wartman LD;Watson MA;Welch J;Wendl MC;Ally A;Balasundaram M;Birol I;Butterfield Y;Chiu R;Chu A;Chuah E;Chun HJ;Corbett R;Dhalla N;Guin R;He A;Hirst C;Hirst M;Holt RA;Jones S;Karsan A;Lee D;Li HI;Marra MA;Mayo M;Moore RA;Mungall K;Parker J;Pleasance E;Plettner P;Schein J;Stoll D;Swanson L;Tam A;Thiessen N;Varhol R;Wye N;Zhao Y;Gabriel S;Getz G;Sougnez C;Zou L;Leiserson MD;Vandin F;Wu HT;Applebaum F;Baylin SB;Akbani R;Broom BM;Chen K;Motter TC;Nguyen K;Weinstein JN;Zhang N;Ferguson ML;Adams C;Black A;Bowen J;Gastier-Foster J;Grossman T;Lichtenberg T;Wise L;Davidsen T;Demchok JA;Shaw KR;Sheth M;Sofia HJ;Yang L;Downing JR;Eley G
通讯作者：
Eley G