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血管生成素-2的致癌功能及其对结直肠癌肿瘤进展的调节作用。

Oncogenic function of angiopoietin-2 and its modulation of tumor progression in colorectal carcinoma.

作者信息

Kim Hyungjoo, Ahn Tae Sung, Kim Chang-Jin, Bae Sang Byung, Kim Han Jo, Lee Chang-Seuk, Kim Tae Hyun, Im Jungkyun, Lee Sang Hun, Son Myoung Won, Lee Moon Soo, Baek Moo Jun, Jeong Dongjun

机构信息

Soonchunhyang Medical Science Research Institute, College of Medicine, Soonchunhyang University, Dongnam-gu, Cheonan, Chungcheongnam-do 330-721, Republic of Korea.

Department of Surgery, College of Medicine, Soonchunhyang University, Dongnam-gu, Cheonan, Chungcheongnam-do 330-721, Republic of Korea.

出版信息

Oncol Lett. 2017 Jul;14(1):553-560. doi: 10.3892/ol.2017.6203. Epub 2017 May 18.

Abstract

Angiopoietin-2 (Ang-2) has been investigated in cancer primarily in terms of its angiogenic function, and its role as an oncogene has yet to be elucidated. The current study hypothesized that Ang-2 may be an oncogene and have a function in tumor progression. An investigation of the function of Ang-2 in the LoVo colorectal cancer (CRC) cell line , which expresses a high level of Ang-2, was performed by knocking down endogenous expression with a targeted short hairpin RNA. The aggressive phenotypic effects of Ang-2 on experimental and control group cells were assessed using cell proliferation, migration and invasion assays. The association between Ang-2 expression levels and clinicopathological factors was evaluated in 415 CRC tissues using immunohistochemistry. Suppressing Ang-2 expression decreased cellular proliferation, invasion and migration in an study. Ang-2 overexpression was observed in 46% of patients with CRC and was significantly associated with pT (P=0.048), pN (P<0.001), venous invasion (P=0.023), lymphatic invasion (P<0.001) and tumor-node-metastasis stage (P=0.022). Furthermore, Ang-2 overexpression was an independent prognostic factor in pN stages 1 and 2. These results reveal that Ang-2 may be an oncogene in colorectal carcinogenesis and its expression may exert aggressive phenotypic effects during tumor progression. In addition, Ang-2 expression may serve as a prognostic marker and a potential drug target.

摘要

血管生成素-2(Ang-2)在癌症研究中主要集中于其血管生成功能,而其作为癌基因的作用尚未阐明。当前研究假设Ang-2可能是一种癌基因并在肿瘤进展中发挥作用。通过用靶向短发夹RNA敲低内源性表达,对高表达Ang-2的LoVo结直肠癌(CRC)细胞系中Ang-2的功能进行了研究。使用细胞增殖、迁移和侵袭试验评估Ang-2对实验组和对照组细胞的侵袭性表型效应。采用免疫组织化学方法评估415例CRC组织中Ang-2表达水平与临床病理因素之间的关联。在一项研究中,抑制Ang-2表达可降低细胞增殖、侵袭和迁移。46%的CRC患者中观察到Ang-2过表达,且与pT(P=0.048)、pN(P<0.001)、静脉侵犯(P=0.023)、淋巴管侵犯(P<0.001)和肿瘤-淋巴结-转移分期(P=0.022)显著相关。此外,Ang-2过表达是pN 1期和2期的独立预后因素。这些结果表明,Ang-2可能是结直肠癌发生中的一种癌基因,其表达可能在肿瘤进展过程中发挥侵袭性表型效应。此外,Ang-2表达可能作为一种预后标志物和潜在的药物靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c2c/5494651/41a377f9e00f/ol-14-01-0553-g00.jpg

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