Zhou Ying, Zhang Xintian, Zhang Jingjing, Fang Jingyuan, Ge Zhizheng, Li Xiaobo
Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University; Shanghai Institute of Digestive Disease, Shanghai, China.
PLoS One. 2017 Apr 4;12(4):e0175122. doi: 10.1371/journal.pone.0175122. eCollection 2017.
Leucine-rich-alpha-2-glycoprotein 1 (LRG1) has been shown to be involved in various human malignancies. Whether it plays a role in colorectal cancer (CRC) development remains unclear. Here, we investigated whether and through what mechanism LRG1 functions in human CRC cells. The plasma level of LRG1 was significantly increased in CRC patients, but it was remarkably decreased in patients with resected colorectal cancers. Meanwhile, both mRNA and protein levels of LRG1 were remarkable overexpressed in CRC tissues than normal tissues. The knockdown of LRG1 significantly inhibited cell proliferation, induced cell cycle arrest at the G0/G1 phase, and promoted apoptosis in SW480 and HCT116 cells in vitro. In addition, LRG1 silencing led to the downregulation of the levels of key cell cycle factors, such as cyclin D1, B, and E and anti-apoptotic B-cell lymphoma-2(Bcl-2). However, it up-regulated the expression of pro-apoptotic Bax and cleaved caspase-3. Furthermore, RUNX1 could be induced by LRG1 in a concentration-dependent manner, while the knockdown of RUNX1 blocked the promotion of the proliferation and inhibition of apoptosis induced by LRG1. Collectively, these findings indicate that LRG1 plays a crucial role in the proliferation and apoptosis of CRC by regulating RUNX1 expression. Thus, LRG1 may be a potential detection biomarker as well as a marker for monitoring recurrence and therapeutic target for CRC.
富含亮氨酸的α-2-糖蛋白1（LRG1）已被证明与多种人类恶性肿瘤有关。它是否在结直肠癌（CRC）的发生发展中起作用仍不清楚。在此，我们研究了LRG1在人CRC细胞中是否发挥作用以及通过何种机制发挥作用。CRC患者血浆中LRG1水平显著升高，但在接受结直肠癌切除的患者中则显著降低。同时，与正常组织相比，CRC组织中LRG1的mRNA和蛋白水平均显著过表达。在体外，敲低LRG1可显著抑制SW480和HCT116细胞的增殖，诱导细胞周期停滞在G0/G1期，并促进细胞凋亡。此外，LRG1沉默导致关键细胞周期因子如细胞周期蛋白D1、B和E以及抗凋亡的B细胞淋巴瘤-2（Bcl-2）水平下调。然而，它上调了促凋亡蛋白Bax和裂解的半胱天冬酶-3的表达。此外，RUNX1可被LRG1以浓度依赖的方式诱导，而敲低RUNX1可阻断LRG1诱导的增殖促进和凋亡抑制作用。总体而言，这些发现表明LRG1通过调节RUNX1表达在CRC的增殖和凋亡中起关键作用。因此，LRG1可能是CRC的一种潜在检测生物标志物以及监测复发的标志物和治疗靶点。
