Wang Song, Liu Zheng, Ma Yi-Ming, Guan Xu, Jiang Zheng, Sun Peng, Liu En-Rui, Zhang Yu-Kun, Wang Hong-Ying, Wang Xi-Shan
Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, P. R. China.
Department of Colorectal Surgery, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China.
Gastroenterol Rep (Oxf). 2020 Jul 25;9(2):166-175. doi: 10.1093/gastro/goaa032. eCollection 2021 Apr.
Some recent studies on insulin receptor tyrosine kinase substrate (IRTKS) have focused more on its functions in diseases. However, there is a lack of research on the role of IRTKS in carcinomas and its mechanism remains ambiguous. In this study, we aimed to clarify the role and mechanism of IRTKS in the carcinogenesis of colorectal cancer (CRC).
We analysed the expression of IRTKS in CRC tissues and normal tissues by researching public databases. Cancer tissues and adjacent tissues of 67 CRC patients who had undergone radical resection were collected from our center. Quantitative real-time polymerase chain reaction and immunohistochemistry were performed in 52 and 15 pairs of samples, respectively. and experiments were conducted to observe the effect of IRTKS on CRC cells. Gene Set Enrichment Analysis and Metascape platforms were used for functional annotation and enrichment analysis. We detected the protein kinase B (AKT) phosphorylation and cell viability of SW480 transfected with small interfering RNAs (siRNAs) with or without basic fibroblast growth factor (bFGF) through immunoblotting and proliferation assays.
The expression of IRTKS in CRC tissues was higher than that in adjacent tissues and normal tissues (all <0.05). Disease-free survival of patients with high expression was shorter. Overexpression of IRTKS significantly increased the proliferation rate of CRC cells and the number of tumor xenografts . The phosphorylation level of AKT in CRC cells transfected with pLVX-IRTKS was higher than that in the control group. Furthermore, siRNA-IRTKS significantly decreased the proliferation rate of tumor cells and the phosphorylation level of AKT induced by bFGF.
IRTKS mediated the bFGF-induced cell proliferation through the phosphorylation of AKT in CRC cells, which may contribute to tumorigenicity .
近期一些关于胰岛素受体酪氨酸激酶底物（IRTKS）的研究更多地聚焦于其在疾病中的功能。然而，关于IRTKS在癌症中的作用缺乏研究，其机制仍不明确。在本研究中，我们旨在阐明IRTKS在结直肠癌（CRC）致癌过程中的作用及机制。
我们通过研究公共数据库分析了CRC组织和正常组织中IRTKS的表达。从我们中心收集了67例接受根治性切除的CRC患者的癌组织和癌旁组织。分别对52对和15对样本进行了定量实时聚合酶链反应和免疫组织化学检测。进行了体外和体内实验以观察IRTKS对CRC细胞的影响。使用基因集富集分析和Metascape平台进行功能注释和富集分析。我们通过免疫印迹和增殖试验检测了转染小干扰RNA（siRNAs）的SW480细胞在有或无碱性成纤维细胞生长因子（bFGF）情况下的蛋白激酶B（AKT）磷酸化水平和细胞活力。
CRC组织中IRTKS的表达高于癌旁组织和正常组织（均P<0.05）。高表达患者的无病生存期较短。IRTKS的过表达显著提高了CRC细胞的增殖率和肿瘤异种移植的数量。转染pLVX-IRTKS的CRC细胞中AKT的磷酸化水平高于对照组。此外，siRNA-IRTKS显著降低了肿瘤细胞的增殖率以及bFGF诱导的AKT磷酸化水平。
IRTKS通过CRC细胞中AKT的磷酸化介导bFGF诱导的细胞增殖，这可能有助于肿瘤发生。
