Up-regulation of REG3A in colorectal cancer cells confers proliferation and correlates with colorectal cancer risk.
Up-regulation of REG3A in colorectal cancer cells confers proliferation and correlates with colorectal cancer risk.
复制标题
结直肠癌细胞中 REG3A 的上调会导致增殖并与结直肠癌风险相关
DOI：
10.18632/oncotarget.6473
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发表时间：
2016-01-26
期刊：
影响因子：
--
通讯作者：
Zhang H
中科院分区：
文献类型：
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作者：
Ye Y;Xiao L;Wang SJ;Yue W;Yin QS;Sun MY;Xia W;Shao ZY;Zhang H
结直肠癌是世界上最常见的恶性肿瘤之一。先前的研究已经调查了各种癌症中再生胰岛衍生3 α（REG 3A）的表达改变。本研究旨在探讨REG 3A在结直肠癌中的生物学功能及其分子机制。在这项研究中，发现REG 3A在CRC中与正常组织相比升高。REG 3A高表达与肿瘤大小、分化程度、分期及生存率相关。在两种大肠癌细胞系LOVO和RKO中，REG 3A的敲低显著抑制细胞增殖，并增加G1期细胞群和细胞凋亡率。我们还发现在CRC细胞中REG 3A的下调显著抑制细胞迁移和侵袭。在The Cancer Genome Atlas数据集上的基因集富集分析显示，京都基因和基因组百科全书（KEGG）DNA复制和碱基切除修复（BER）途径与REG 3A表达相关，Western blot进一步证实了这一点。此外，我们证实了REG 3A和纤维连接蛋白在CRC细胞中的相互作用。我们还发现REG 3A表达水平与AKT和ERK 1/2磷酸化状态呈正相关。这些数据表明REG 3A过表达通过激活AKT和ERK 1/2通路促进CRC肿瘤发生。REG 3A可能作为一个有前途的治疗策略CRC。
Colorectal cancer (CRC) is one of the most common malignancies in the world. Previous studies have investigated the altered expression of regenerating islet-derived 3 alpha (REG3A) in various cancers. We aimed at exploring the biological function and the underlying molecular mechanism of REG3A in CRC. In this study, REG3A was found elevated in CRC compared with normal tissues. Further, high REG3A expression level was correlated with bigger tumor size, poorer differentiation, higher tumor stage and lower survival rate. Knockdown of REG3A in two CRC cell lines, LOVO and RKO, significantly inhibited cell proliferation, and increased cells population in G1 phase and cell apoptotic rate. We also found that down-regulation of REG3A in CRC cells notably inhibited cell migration and invasion. Gene set enrichment analysis on The Cancer Genome Atlas dataset showed that Kyoto Encyclopedia of Genes and Genomes (KEGG) DNA replication and base excision repair (BER) pathways were correlative with the REG3A expression, which was further confirmed in CRC cells by Western blot. Moreover, we confirmed the interaction of REG3A and fibronectin in CRC cells. We also found that there was a positive correlation between REG3A expression level and the AKT and ERK1/2 phosphorylation status. These collective data indicated that REG3A overexpression promotes CRC tumorigenesis by activating AKT and ERK1/2 pathways. REG3A may serve as a promising therapeutic strategy for CRC.