Abstract

Colorectal cancer (CRC) is one of the most lethal cancers worldwide. The expression of β-arrestin2 (β-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.

中文翻译：

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ARRB2通过触发WTAP促进结直肠癌生长

 抽象的

结直肠癌（CRC）是全世界最致命的癌症之一。 β-arrestin2 (β-Arr2, ARRB2) 在结直肠癌中的表达已得到充分研究；然而，其导致癌症进展的确切机制仍不清楚。在本研究中，我们通过癌症基因组图谱（TCGA）数据、蛋白质印迹分析和免疫组织化学发现，与正常组织相比，结直肠癌中ARRB2的表达水平显着上调。此外，通过 Kaplan-Meier 分析，ARRB2 水平与患者的总生存期相关。 ARRB2的高表达促进CRC细胞生长，增强细胞运动性，并阻止细胞凋亡，这对肿瘤生长至关重要。最后，抑制 ARRB2 表达足以减弱氧化偶氮甲烷/葡聚糖硫酸钠诱导的 CRC 的进展。有趣的是，我们还发现 ARRB2 的敲除减少了由 Wilms 肿瘤 1 相关蛋白（WTAP）表达介导的多种癌症途径，从而抑制细胞增殖和迁移。总而言之，我们的结果表明 ARRB2 通过调节 WTAP 表达促进 CRC 细胞的生长和迁移。