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干扰素诱导蛋白 27 促进上皮-间充质转化,诱导卵巢肿瘤发生和干性。

Interferon alpha-inducible protein 27 promotes epithelial-mesenchymal transition and induces ovarian tumorigenicity and stemness.

机构信息

Department of Obstetrics and Gynecology, Yijishan Hospital, Wannan Medical College, Wuhu, China.

Department of Obstetrics and Gynecology, Yangpu District Central Hospital, Shanghai, China.

出版信息

J Surg Res. 2015 Jan;193(1):255-64. doi: 10.1016/j.jss.2014.06.055. Epub 2014 Jul 5.

Abstract

BACKGROUND

Interferon alpha-inducible protein 27 (IFI27) is an interferon alpha-inducible protein, which was found to be upregulated in some cancers, such as breast cancer, squamous cell carcinoma, hepatocellular carcinoma, and serous ovarian carcinoma. However, the role of IFI27 in ovarian cancer remains to be elucidated. This study was designed to investigate the role of IFI27 in ovarian cancer tumorigenicity.

MATERIALS AND METHODS

The expression of IFI27 was examined in ovarian cancer tissues and cell lines by real time quantitative reverse transcription polymerase chain reaction and immunohistochemistry. The cell migration and invasion was investigated by wound healing and transwell invasion assay. The epithelial-mesenchymal transition markers were detected by Western blotting and the stemness was evaluated by sphere formation. The tumor growth was examined in the athymic mice model.

RESULTS

We found that IFI27 is overexpressed in ovarian cancer and associated with patients' survival. Interestingly, we further observed that the expression of IFI27 was associated with the expression of mesenchymal marker vimentin in ovarian cancer. Overexpression of IFI27 induces epithelial-mesenchymal transition and promotes epithelial ovarian cancer cells migration and invasion, tumorigenicity, stemness, and drug resistance. Moreover, overexpression of IFI27 is associated with loss of miR-502 in ovarian cancer. Reexpression of miR-502 inhibits IFI27-induced tumorigenicity, migration, and drug resistance.

CONCLUSIONS

These data suggested that IFI27 may be a potential target for developing novel diagnosis strategies and therapeutic interventions.

摘要

背景

干扰素诱导蛋白 27(IFI27)是一种干扰素诱导蛋白,在某些癌症中如乳腺癌、鳞状细胞癌、肝癌和浆液性卵巢癌中发现其上调。然而,IFI27 在卵巢癌中的作用仍需阐明。本研究旨在研究 IFI27 在卵巢癌肿瘤发生中的作用。

材料与方法

通过实时定量逆转录聚合酶链反应和免疫组织化学检测卵巢癌组织和细胞系中 IFI27 的表达。通过划痕愈合和 Transwell 侵袭实验研究细胞迁移和侵袭。通过 Western blot 检测上皮-间充质转化标志物,通过球体形成评估干性。在免疫缺陷小鼠模型中检测肿瘤生长。

结果

我们发现 IFI27 在卵巢癌中过度表达,并与患者的生存相关。有趣的是,我们进一步观察到 IFI27 的表达与卵巢癌中间充质标志物波形蛋白的表达相关。IFI27 的过表达诱导上皮-间充质转化,并促进上皮性卵巢癌细胞迁移和侵袭、肿瘤发生、干性和耐药性。此外,IFI27 的过表达与卵巢癌中 miR-502 的缺失相关。miR-502 的重新表达抑制 IFI27 诱导的肿瘤发生、迁移和耐药性。

结论

这些数据表明,IFI27 可能是开发新的诊断策略和治疗干预措施的潜在靶点。

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