ABI1-TSV-11 表达在左侧结直肠癌患者中的作用和预后意义。
The roles and prognostic significance of ABI1-TSV-11 expression in patients with left-sided colorectal cancer.
机构信息
Department of Central Laboratory and Institute of Clinical Molecular Biology, Peking University People's Hospital, Beijing, China.
Department of Gastroenterology, Peking University People's Hospital, Beijing, China.
出版信息
Sci Rep. 2021 May 24;11(1):10734. doi: 10.1038/s41598-021-90220-8.
Abnormally expressed and/or phosphorylated Abelson interactor 1 (ABI1) participates in the metastasis and progression of colorectal cancer (CRC). ABI1 presents as at least 12 transcript variants (TSVs) by mRNA alternative splicing, but it is unknown which of them is involved in CRC metastasis and prognosis. Here, we firstly identified ABI1-TSV-11 as a key TSV affecting the metastasis and prognosis of left-sided colorectal cancer (LsCC) and its elevated expression is related to lymph node metastasis and shorter overall survival (OS) in LsCC by analyzing data from The Cancer Genome Atlas and TSVdb. Secondly, ABI1-TSV-11 overexpression promoted LoVo and SW480 cells adhesion and migration in vitro, and accelerated LoVo and SW480 cells lung metastasis in vivo. Finally, mechanism investigations revealed that ABI1-isoform-11 interacted with epidermal growth factor receptor pathway substrate 8 (ESP8) and regulated actin dynamics to affect LoVo and SW480 cells biological behaviors. Taken together, our data demonstrated that ABI1-TSV-11 plays an oncogenic role in LsCC, it is an independent risk factor of prognosis and may be a potential molecular marker and therapeutic target in LsCC.
异常表达和/或磷酸化的 Abelson 相互作用蛋白 1（ABI1）参与结直肠癌（CRC）的转移和进展。ABI1 通过 mRNA 选择性剪接呈现至少 12 种转录变体（TSV），但尚不清楚其中哪一种参与 CRC 转移和预后。在这里，我们首先通过分析来自癌症基因组图谱（The Cancer Genome Atlas，TCGA）和 TSVdb 的数据，确定 ABI1-TSV-11 是影响左侧结直肠癌（left-sided colorectal cancer，LsCC）转移和预后的关键 TSV，其高表达与 LsCC 的淋巴结转移和总生存期（overall survival，OS）缩短有关。其次，ABI1-TSV-11 的过表达促进了 LoVo 和 SW480 细胞的体外黏附和迁移，并在体内加速了 LoVo 和 SW480 细胞的肺转移。最后，机制研究表明，ABI1-异构体-11 与表皮生长因子受体途径底物 8（epidermal growth factor receptor pathway substrate 8，ESP8）相互作用，调节肌动蛋白动力学，从而影响 LoVo 和 SW480 细胞的生物学行为。总之，我们的数据表明 ABI1-TSV-11 在 LsCC 中发挥致癌作用，是预后的独立危险因素，可能是 LsCC 潜在的分子标志物和治疗靶点。
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