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干扰素诱导跨膜蛋白2是结直肠癌的一个预后标志物,并通过激活PI3K/AKT通路促进其进展。

Interferon-induced transmembrane protein 2 is a prognostic marker in colorectal cancer and promotes its progression by activating the PI3K/AKT pathway.

作者信息

Liu Yonggang, Liang Jiyun, Li Xi, Huang Junyong, Huang Jiangyuan, Wang Jiale

机构信息

Department of Oncology, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde), No.1 Jiazi Road, Shunde District, Foshan, 528308, Guangdong, People's Republic of China.

出版信息

Discov Oncol. 2024 May 27;15(1):191. doi: 10.1007/s12672-024-01040-x.

Abstract

BACKGROUND

Interferon-induced transmembrane protein 2 (IFITM2) is involved in repressing viral infection. This study aim to investigate the expression of IFITM2 in colorectal cancer (CRC) and explore its effect on cell proliferation, migration, and invasion.

METHODS

We analyzed The Cancer Genome Atlas (TCGA) database for IFITM2 expression in colorectal cancer and used western blots to detect IFITM2 protein in specimens and cell lines of colorectal cancers. To assess the association between IFITM2 and clinical features, both univariate and multivariate cox regression analysis were conducted. Kaplan-Meier plots were used in the TCGA database to assess IFITM2 gene expression's prognostic significance. Silencing IFITM2 in SW480 and HCT116 cells was achieved by transient transfection with siRNA. Proliferation of CRCs was examined using Cell Counting Kit-8. The effect of IFITM2 on the migration and invasion of CRC cells was studied using wound healing and transwell assays. Gene set enrichment analysis (GSEA) was used to examine IFITM2-associated pathways and Western blotting was used to confirm it.

RESULTS

IFITM2 was over-expressed in the CRC tissues and cells, with high IFITM2 expression related to the tumor N, M, and pathologic stages. The presence of IFITM2 significantly impacted patient survival in CRC. The proliferation of SW480 and HCT116 cells was suppressed when IFITM2 was silenced, resulting in weakened migration and invasion of CRC cells. GSEA analysis showed that IFITM2 was positively related to the phosphoinositide 3-kinase (PI3K)/AKT pathway, and western blot results confirmed that IFITM2 activated it.

CONCLUSIONS

IFITM2 was over-expressed in CRC and modulated the PI3K/AKT pathway to promote CRC cells proliferation and metastasis.

摘要

背景

干扰素诱导跨膜蛋白2(IFITM2)参与抑制病毒感染。本研究旨在探讨IFITM2在结直肠癌(CRC)中的表达情况,并探究其对细胞增殖、迁移和侵袭的影响。

方法

我们分析了癌症基因组图谱(TCGA)数据库中结直肠癌中IFITM2的表达情况,并使用蛋白质免疫印迹法检测了结直肠癌标本和细胞系中的IFITM2蛋白。为评估IFITM2与临床特征之间的关联,进行了单因素和多因素cox回归分析。在TCGA数据库中使用Kaplan-Meier曲线评估IFITM2基因表达的预后意义。通过用小干扰RNA(siRNA)瞬时转染实现SW480和HCT116细胞中IFITM2的沉默。使用细胞计数试剂盒-8检测结直肠癌的增殖情况。使用伤口愈合实验和Transwell实验研究IFITM2对结直肠癌细胞迁移和侵袭的影响。使用基因集富集分析(GSEA)检测与IFITM2相关的信号通路,并通过蛋白质免疫印迹法进行验证。

结果

IFITM2在结直肠癌组织和细胞中高表达,且IFITM2高表达与肿瘤的N、M分期及病理分期相关。IFITM2的存在显著影响结直肠癌患者的生存。当IFITM2沉默时,SW480和HCT116细胞的增殖受到抑制,导致结直肠癌细胞的迁移和侵袭能力减弱。GSEA分析表明,IFITM2与磷酸肌醇3激酶(PI3K)/蛋白激酶B(AKT)信号通路呈正相关,蛋白质免疫印迹结果证实IFITM2激活了该信号通路。

结论

IFITM2在结直肠癌中高表达,并通过调节PI3K/AKT信号通路促进结直肠癌细胞的增殖和转移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d19d/11130111/9358f16c6bf3/12672_2024_1040_Fig1_HTML.jpg

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