The phosphoinositide hydrolase phospholipase C delta1 inhibits epithelial-mesenchymal transition and is silenced in colorectal cancer
The phosphoinositide hydrolase phospholipase C delta1 inhibits epithelial-mesenchymal transition and is silenced in colorectal cancer
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磷酸肌醇水解酶磷脂酶 C delta1 抑制上皮间质转化并在结直肠癌中被沉默
DOI：
10.1002/jcp.28073
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发表时间：
2019-08-01
影响因子：
5.6
通讯作者：
Peng, Weiyan
中科院分区：
文献类型：
--
作者：
Xiang, Qin;He, Xiaoqian;Peng, Weiyan
在这项研究中，我们发现，磷脂酶C δ 1（PLCD 1）蛋白表达减少，结直肠肿瘤组织相比，配对的手术切缘组织。在29/64例（45%）原发性结直肠肿瘤中检测到PLCD 1促进的CpG甲基化，但在非肿瘤组织中未检测到。由于PLCD 1甲基化，6个细胞系中有3个的PLCD 1 RNA表达也降低。PLCD 1的异位表达抑制了大肠癌细胞的增殖和迁移，但促进了大肠癌细胞的凋亡。我们还观察到，PLCD 1抑制增殖和促进凋亡在体内。此外，PLCD 1诱导G1/S期细胞周期阻滞。此外，我们发现，PLCD 1导致的-catenin，包括c-Myc和细胞周期蛋白D1，这是通常已知的肿瘤发生的启动子下游的几个因素的下调。这种下调是由结肠直肠肿瘤细胞中E-钙粘蛋白的上调引起的。我们的研究结果提供了深入了解PLCD 1作为肿瘤抑制基因在结直肠癌（CRC）中的作用，并证明它在增殖，迁移，侵袭，细胞周期进展和上皮-间质转化中起着重要作用。在这些结果的基础上，PLCD 1的肿瘤特异性甲基化可用作CRC早期检测和预后预测的新生物标志物。
In this study, we found that the phospholipase C delta1 (PLCD1) protein expression is reduced in colorectal tumor tissues compared with paired surgical margin tissues. PLCD1-promoted CpG methylation was detected in 29/64 (45%) primary colorectal tumors, but not in nontumor tissues. The PLCD1 RNA expression was also reduced in three out of six cell lines, due to PLCD1 methylation. The ectopic expression of PLCD1 resulted in inhibited proliferation and attenuated migration of colorectal tumor cells, yet promoted colorectal tumor cell apoptosis in vitro. We also observed that PLCD1 suppressed proliferation and promoted apoptosis in vivo. In addition, PLCD1 induced G1/S phase cell cycle arrest. Furthermore, we found that PLCD1 led to the downregulation of several factors downstream of -catenin, including c-Myc and cyclin D1, which are generally known to be promoters of tumorigenesis. This downregulation was caused by an upregulation of E-cadherin in colorectal tumor cells. Our findings provide insights into the role of PLCD1 as a tumor suppressor gene in colorectal cancer (CRC), and demonstrate that it plays significant roles in proliferation, migration, invasion, cell cycle progression, and epithelial-mesenchymal transition. On the basis of these results, tumor-specific methylation of PLCD1 could be used as a novel biomarker for early detection and prognostic prediction in CRC.