LPLUNC1 inhibits nasopharyngeal carcinoma cell growth via down-regulation of the MAP kinase and cyclin D1/E2F pathways.
LPLUNC1 inhibits nasopharyngeal carcinoma cell growth via down-regulation of the MAP kinase and cyclin D1/E2F pathways.
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LPLUNC1 通过下调 MAP 激酶和细胞周期蛋白 D1/E2F 通路抑制鼻咽癌细胞生长
DOI：
10.1371/journal.pone.0062869
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Li G
中科院分区：
文献类型：
--
作者：
Yang Y;Liao Q;Wei F;Li X;Zhang W;Fan S;Shi L;Li X;Gong Z;Ma J;Zhou M;Xiang J;Peng S;Xiang B;Deng H;Yang Y;Li Y;Xiong W;Zeng Z;Li G
长腭、肺和鼻上皮克隆1(LPLUN1)基因的表达具有组织特异性。在非肿瘤鼻咽上皮组织中高表达，而在鼻咽癌组织中表达降低，提示其可能与鼻咽癌的发生有关。为研究LPLunc1基因在鼻咽癌发生发展中的作用，将其全长表达载体稳定地导入鼻咽癌细胞系5-8F中。结果表明，LPLunc1在体外抑制鼻咽癌细胞的增殖，在体内抑制肿瘤的形成。LPLUN1还可延缓细胞周期由G1期进入S期，并抑制细胞周期蛋白D1、细胞周期蛋白依赖性激酶4(CDK4)和磷酸化Rb的表达。为了进一步研究LPLunc1抑制鼻咽癌发生的分子机制，采用了基因芯片技术。这些研究表明，LPLUN1抑制某些丝裂原活化蛋白(MAP)激酶(MAPK)和细胞周期相关分子的表达。Western blotting证实LPLUN1抑制MEK1、磷酸化ERK1/2、磷酸化JNK1/2、c-Myc和c-Jun的表达。此外，AP-1的转录活性被LPLUN1下调，提示MAPK信号通路受LPLUN1的调控。综上所述，本研究表明LPLUN1通过抑制MAPK和细胞周期蛋白D1/E2F通路而延缓鼻咽癌细胞的生长，提示LPLUN1可能是与鼻咽癌相关的候选抑癌基因。
Long-palate, lung and nasal epithelium clone 1 (LPLUNC1) gene expression is relatively tissue specific. It is highly expressed in nontumor nasopharyngeal epithelial tissues, but its expression is reduced in nasopharyngeal carcinoma (NPC), indicating that LPLUNC1 may be associated with the tumorigenesis of NPC. To study the effects of LPLUNC1 on NPC tumorigenesis, a full-length LPLUNC1 expression plasmid was stably transfected into the NPC cell line, 5-8F. Our data indicated that LPLUNC1 inhibited NPC cell proliferation in vitro and tumor formation in vivo. LPLUNC1 also delayed cell cycle progression from G1 to S phase and inhibited the expression of cyclin D1, cyclin-dependent kinase 4 (CDK4) and phosphorylated Rb. To further investigate the molecular mechanisms underlying the suppressive effects of LPLUNC1 on NPC tumorigenesis, cDNA microarray was performed. These studies revealed that LPLUNC1 inhibited the expression of certain mitogen-activated protein (MAP) kinases (MAPK) kinases and cell cycle-related molecules. Western blotting confirmed that the expression of MEK1, phosphorylated ERK1/2, phosphorylated JNK1/2, c-Myc and c-Jun were inhibited by LPLUNC1. Furthermore, the transcriptional activity of AP-1 was down-regulated by LPLUNC1, suggesting that the MAPK signaling pathway is regulated by LPLUNC1. Taken together, the present study indicates that LPLUNC1 delays NPC cell growth by inhibiting the MAPK and cyclin D1/E2F pathways and suggests that LPLUNC1 may represent a promising candidate tumor suppressor gene associated with NPC.
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