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IGF2BP3 表达增加促进结直肠癌细胞在体外和体内的侵袭表型。

Increased IGF2BP3 expression promotes the aggressive phenotypes of colorectal cancer cells in vitro and vivo.

机构信息

Department of Colorectal Surgery, Xin-Hua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Shanghai Colorectal Cancer Research Center, Shanghai, China.

出版信息

J Cell Physiol. 2019 Aug;234(10):18466-18479. doi: 10.1002/jcp.28483. Epub 2019 Mar 20.

Abstract

Previous literatures reported insulin-like growth factor-2 messenger RNA-binding protein 3 (IGF2BP3) is a poor prognostic marker for colorectal cancer (CRC) patients. However, basic research on the effect and biological role of IGF2BP3 in CRC was still scare. Real-time quantitative polymerase chain reaction and western blot analysis were used to examine IGF2BP3 expression level in tumors and paired normal tissues from CRC patients. Tissue microarrays with 192 CRC patients were subjected to immunohistochemical staining to analyze the prognostic value of IGF2BP3. Proliferation assays, migration assays, and xenograft tumor formation in nude mice were performed to assess the biological role of IGF2BP3 in CRC cells. IGF2BP3 expression was significantly upregulated in tumor tissues compared with the matched normal tissues both in messenger RNA and protein level and was associated with worse prognosis. IGF2BP3 knockdown made cell cycle arrest to impair the proliferation ability of CRC cells and further inhibited the xenograft tumor growth in nude mice, also inhibited the migration ability of CRC cells via inducing epithelial-mesenchymal transition. Therefore, the research demonstrated that increased IGF2BP3 expression promoted the aggressive phenotypes of CRC cells. Targeted IGF2BP3 could be a novel and effective gene therapy for CRC patients to make a better prognosis.

摘要

先前的文献报道胰岛素样生长因子 2 信使 RNA 结合蛋白 3(IGF2BP3)是结直肠癌(CRC)患者预后不良的标志物。然而,关于 IGF2BP3 在 CRC 中的作用和生物学功能的基础研究仍然很少。实时定量聚合酶链反应和 Western blot 分析用于检测 CRC 患者肿瘤和配对正常组织中的 IGF2BP3 表达水平。对 192 例 CRC 患者的组织微阵列进行免疫组织化学染色,分析 IGF2BP3 的预后价值。进行增殖试验、迁移试验和裸鼠异种移植肿瘤形成试验,以评估 IGF2BP3 在 CRC 细胞中的生物学作用。IGF2BP3 在信使 RNA 和蛋白水平上均在肿瘤组织中显著上调,与预后不良相关。IGF2BP3 敲低导致细胞周期停滞,从而损害 CRC 细胞的增殖能力,并进一步抑制裸鼠异种移植肿瘤的生长,还通过诱导上皮-间充质转化抑制 CRC 细胞的迁移能力。因此,该研究表明,IGF2BP3 的表达增加促进了 CRC 细胞的侵袭表型。靶向 IGF2BP3 可能是 CRC 患者的一种新型有效基因治疗方法,以获得更好的预后。

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