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ITGBL1 促进结直肠癌的迁移和侵袭,并预测不良预后。

ITGBL1 promotes migration, invasion and predicts a poor prognosis in colorectal cancer.

机构信息

Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, PR China; The Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Diseases, Wuhan, Hubei, 430071, PR China.

Department of Gastroenterology, The Second People's Hospital of Shenzhen, The First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, 518035, PR China.

出版信息

Biomed Pharmacother. 2018 Aug;104:172-180. doi: 10.1016/j.biopha.2018.05.033. Epub 2018 May 15.

DOI:10.1016/j.biopha.2018.05.033
PMID:29772438
Abstract

Colorectal cancer (CRC) is one of the most common malignancies worldwide; its progression and prognosis are associated with oncogenes. The present study aimed to identify differentially expressed genes (DEGs) and explore the role and potential mechanism of integrin subunit β like 1 (ITGBL1) in CRC. The microarray dataset GSE41258 was used to screen DEGs involved in CRC. Survival analysis was performed to predict the prognosis of CRC patients. To validate ITGBL1 expression, immunohistochemistry, quantitative real-time PCR and western blotting were performed in CRC tissues and cells. Subsequently, the effects of ITGBL1 were evaluated through colony formation, cell proliferation, migration and invasion assays. Finally, we took advantage of Gene Ontology (GO) analysis and Gene Set Enrichment Analysis (GSEA) to explore potential function and mechanism of ITGBL1 in CRC. In our study, 182 primary CRC tissues and 54 normal colon tissues were contained in GSE41258 dataset. A total of 318 DEGs were screened, among which ITGBL1 was found to be significantly up-regulated in CRC, and its high expression was associated with shortened survival of CRC patients. Moreover, knockdown of ITGBL1 promoted CRC cell proliferation, migration and invasion. Finally, GO analysis revealed that ITGBL1 was associated with cell adhesion. GSEA indicated that ITGBL1 was enriched in ECM receptor interaction and focal adhesion. In conclusion, a novel oncogene ITGBL1 was identified and demonstrated to be associated with the progression and prognosis of CRC, which might be a potential therapeutic target and prognostic biomarker for CRC patients.

摘要

结直肠癌(CRC)是全球最常见的恶性肿瘤之一;其进展和预后与癌基因有关。本研究旨在鉴定差异表达基因(DEGs),并探讨整合素亚基β样 1(ITGBL1)在 CRC 中的作用和潜在机制。使用微阵列数据集 GSE41258 筛选涉及 CRC 的 DEGs。进行生存分析以预测 CRC 患者的预后。为了验证 ITGBL1 的表达,在 CRC 组织和细胞中进行了免疫组织化学、定量实时 PCR 和 Western blot 检测。随后,通过集落形成、细胞增殖、迁移和侵袭实验评估 ITGBL1 的作用。最后,我们利用基因本体论(GO)分析和基因集富集分析(GSEA)探讨 ITGBL1 在 CRC 中的潜在功能和机制。在我们的研究中,GSE41258 数据集包含了 182 例原发性 CRC 组织和 54 例正常结肠组织。筛选出了 318 个差异表达基因,其中 ITGBL1 在 CRC 中明显上调,其高表达与 CRC 患者的生存时间缩短有关。此外,敲低 ITGBL1 促进了 CRC 细胞的增殖、迁移和侵袭。最后,GO 分析表明 ITGBL1 与细胞黏附有关。GSEA 表明 ITGBL1 富集在 ECM 受体相互作用和焦点黏附中。总之,鉴定了一个新的癌基因 ITGBL1,并证明其与 CRC 的进展和预后有关,它可能是 CRC 患者潜在的治疗靶点和预后生物标志物。

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