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三结构域蛋白 59(TRIM59)在肝内胆管癌增殖和预后中的作用。

The role of Tripartite motif containing 59 (TRIM59) in the proliferation and prognosis of intrahepatic cholangiocarcinoma.

机构信息

The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai 200438, China; Changzheng Hospital, Second Military Medical University (Naval Medical University), Shanghai, China.

The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai 200438, China.

出版信息

Pathol Res Pract. 2022 Aug;236:153989. doi: 10.1016/j.prp.2022.153989. Epub 2022 Jun 17.

DOI:10.1016/j.prp.2022.153989
PMID:35753134
Abstract

Tripartite motif containing 59 (TRIM59) is a crucial gene that is involved in the process of various types of cancer,including breast cancer, lung cancer, colorectal cancer,and so on. Its abnormal expression can affect tumor cell proliferation, metastasis, or apoptosis. In liver cancer, the incidence of intrahepatic cholangiocarcinoma (ICC) is increasing. However, However, it has not been clearly reported on TRIM59 affects the progress of intrahepatic cholangiocarcinoma cells.Firstly, we review the expression of TRIM59 in different cancers and the corresponding normal tissues,and the results preliminarily showed that TRIM59 may be abnormally expressed in many cancers. The author focuses on whether TRIM59 plays a crucial biological role in intrahepatic cholangiocarcinoma. Therefore, we have confirmed through online websites that TRIM59 is highly expressed in intrahepatic cholangiocarcinoma tissues. Furthermore we further found that TRIM59 can be used as an effective prognostic marker for the prognostic guidance of patient survival time. Next, we explore whether the expression level of TRIM59 in intrahepatic cholangiocarcinoma is related to proliferation through the CCK-8 and EDU assay in two ICC cell lines. To further explore how TRIM59 affected the molecular mechanism involved in intrahepatic cholangiocarcinoma cell growth, we found that STAT3 promotes TRIM59 transcription and TRIM59 can affect tumor progression by regulating the PI3K/AKT signaling pathway through luciferase reporter assay and Western blot experiments. In summary, we first found that TRIM59 has great research value in ICC through bioinformatic analysis, then its expression level is closely related to the prognosis through the analysis of clinicopathological indicators of patients with ICC, and the biological mechanism of TRIM59 in ICC provides precise research or therapeutic targets for future cancer treatment. The findings improve our understanding of the potential of TRIM59 in biological functions in ICC and may hold promise as markers for the diagnosis,treatment, and prognosis of ICC. DATA AVAILABILITY: The raw data of this study are derived from the TCGA database, which are publicly available databases.

摘要

三结构域蛋白 59(TRIM59)是一种关键基因,参与多种类型的癌症,包括乳腺癌、肺癌、结直肠癌等。其异常表达可影响肿瘤细胞的增殖、转移或凋亡。在肝癌中,肝内胆管癌(ICC)的发病率正在增加。然而,TRIM59 如何影响肝内胆管癌细胞的进展尚未得到明确报道。首先,我们回顾了 TRIM59 在不同癌症及相应正常组织中的表达情况,结果初步表明,TRIM59 可能在许多癌症中异常表达。作者主要关注 TRIM59 在肝内胆管癌中是否发挥关键的生物学作用。因此,我们通过在线网站证实 TRIM59 在肝内胆管癌组织中高表达。此外,我们进一步发现 TRIM59 可作为患者生存时间预后指导的有效预后标志物。接下来,我们通过在两种 ICC 细胞系中进行 CCK-8 和 EDU 检测,探讨肝内胆管癌中 TRIM59 的表达水平与增殖的关系。为了进一步探讨 TRIM59 如何影响肝内胆管癌细胞生长所涉及的分子机制,我们发现 STAT3 促进 TRIM59 转录,TRIM59 通过荧光素酶报告基因检测和 Western blot 实验证实可以通过调节 PI3K/AKT 信号通路影响肿瘤进展。总之,我们通过生物信息学分析首次发现 TRIM59 在 ICC 中有很大的研究价值,然后通过分析 ICC 患者的临床病理指标发现其表达水平与预后密切相关,TRIM59 在 ICC 中的生物学机制为未来癌症治疗提供了精确的研究或治疗靶点。这些发现提高了我们对 TRIM59 在 ICC 中生物学功能的潜在认识,并可能成为 ICC 诊断、治疗和预后的标志物。数据可用性:本研究的原始数据来自 TCGA 数据库,这是公开可用的数据库。

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