Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
PLoS One. 2013 May 1;8(5):e62869. doi: 10.1371/journal.pone.0062869. Print 2013.
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.
长腭、肺和鼻上皮细胞克隆 1（LPLUNC1）基因的表达具有相对组织特异性。它在非肿瘤性鼻咽上皮组织中高度表达，但在鼻咽癌（NPC）中表达降低，表明 LPLUNC1 可能与 NPC 的肿瘤发生有关。为了研究 LPLUNC1 对 NPC 肿瘤发生的影响，我们将全长 LPLUNC1 表达质粒稳定转染到 NPC 细胞系 5-8F 中。我们的数据表明，LPLUNC1 抑制 NPC 细胞在体外的增殖和体内的肿瘤形成。LPLUNC1 还延迟细胞周期从 G1 期到 S 期的进展，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 NPC 肿瘤发生的分子机制，我们进行了 cDNA 微阵列分析。这些研究表明，LPLUNC1 抑制了某些丝裂原激活蛋白（MAP）激酶（MAPK）激酶和细胞周期相关分子的表达。Western blot 证实，LPLUNC1 抑制了 MEK1、磷酸化 ERK1/2、磷酸化 JNK1/2、c-Myc 和 c-Jun 的表达。此外，LPLUNC1 下调了 AP-1 的转录活性，表明 MAPK 信号通路受 LPLUNC1 调节。综上所述，本研究表明 LPLUNC1 通过抑制 MAPK 和细胞周期蛋白 D1/E2F 通路延迟 NPC 细胞生长，并表明 LPLUNC1 可能代表与 NPC 相关的有前途的候选肿瘤抑制基因。
