ARRB2 promotes colorectal cancer growth through triggering WTAP
ARRB2 promotes colorectal cancer growth through triggering WTAP
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DOI：
10.1093/abbs/gmaa151
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发表时间：
2021-01-01
影响因子：
3.7
通讯作者：
Zeng, Lixian
中科院分区：
文献类型：
--
作者：
Liang, Hongguang;Lin, Zelong;Zeng, Lixian
结直肠癌（CRC）是世界上最致命的癌症之一。β-arrestin 2（beta-Arr 2，ARRB 2）在结直肠癌中的表达已得到充分研究，但其导致肿瘤进展的确切机制尚不清楚。在这项研究中，我们发现，ARRB 2的表达水平显着上调CRC相比，正常组织，采用癌症基因组图谱（TCGA）的数据，蛋白质印迹分析，免疫组化。Kaplan-Meier分析显示ARRB 2水平与患者的总生存期相关。ARRB 2的高表达促进了CRC细胞的生长，增强了细胞的运动性，并阻止了细胞凋亡，这对肿瘤的生长至关重要。最后，ARRB 2表达的抑制足以减弱由氧化偶氮甲烷/葡聚糖硫酸钠诱导的CRC的进展。有趣的是，我们还发现ARRB 2的敲低降低了由Wilms肿瘤1相关蛋白（WTAP）表达介导的几种癌症途径，这导致了细胞增殖和迁移的抑制。总之，我们的结果表明，ARRB 2通过调节WTAP表达促进CRC细胞的生长和迁移。
Colorectal cancer (CRC) is one of the most lethal cancers worldwide. The expression of beta-arrestin2 (beta-Arr2, ARRB2) in CRC has been well investigated; however, its exact mechanism causing the cancer progression remains unclear. In this study, we discovered that the expression level of ARRB2 was significantly upregulated in CRC as compared to the normal tissues by employing the Cancer Genome Atlas (TCGA) data, western blot analysis, and immunohistochemistry. Furthermore, the level of ARRB2 was correlated with the patients' overall survival by Kaplan-Meier analysis. The higher expression of ARRB2 promoted CRC cell growth, enhanced the cell motility, and blocked cell apoptosis, which is crucial for tumor growth. Lastly, the suppression of ARRB2 expression was enough to attenuate the progression of CRC induced by azoxymethane/dextran sodium sulfate. Interestingly, we also found that the knockdown of ARRB2 decreased several cancer pathways mediated by the expression of Wilms tumor 1 associated protein (WTAP), which led to the inhibition of cell proliferation and migration. Altogether, our results demonstrated that ARRB2 promoted the growth and migration of CRC cells by regulating the WTAP expression.