泛分析鉴定紫杉醇通过调控 JUN 逆转人胃癌细胞对曲妥珠单抗的耐药性。

Paclitaxel reversed trastuzumab resistance via regulating JUN in human gastric cancer cells identified by FAN analysis.

机构信息

Medical Oncology Department of Gastrointestinal Cancer (1), Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Dadong District, Shenyang, Liaoning Province, 110042, PR China.

Department of Pediatrics First Hospital of Jilin University, No.71 Xinmin Street, Chaoyang District, Changchun, Jilin Province, 130021, PR China.

出版信息

Future Oncol. 2018 Nov;14(26):2701-2712. doi: 10.2217/fon-2018-0127. Epub 2018 Sep 28.

DOI:10.2217/fon-2018-0127

PMID:30265158

Abstract

AIM

In this study, we aim to use bioinformatics approach to identify paclitaxel-targeted modulators potentially involved in the process of reversing the trastuzumab resistance. Materials & methods: We extracted data from GSE77346 to identify potential trastuzumab resistance-related genes, used bioinformatics analysis and functional/activity network approach to find genes involved in trastuzumab resistance reversal.

RESULTS

We identified hub differentially expressed genes related to trastuzumab resistance, trastuzumab targeting and paclitaxel targeting, respectively. We then found C-Jun may be critical in trastuzumab resistance reversal. This process may involve transcriptional activation of DUSP1 by JUN, which lead to regulation of DUSP1-related signaling pathways.

CONCLUSION

The present study revealed paclitaxel may reverse the trastuzumab resistance by JUN, which possibly in turn regulated DUSP1 and DUSP1-related signaling pathways.

摘要

目的

本研究旨在采用生物信息学方法鉴定可能参与逆转曲妥珠单抗耐药过程的紫杉醇靶向调节剂。材料与方法：我们从 GSE77346 中提取数据，以鉴定潜在的与曲妥珠单抗耐药相关的基因，然后使用生物信息学分析和功能/活性网络方法寻找参与逆转曲妥珠单抗耐药的基因。结果：我们分别鉴定了与曲妥珠单抗耐药、曲妥珠单抗靶向和紫杉醇靶向相关的关键差异表达基因。然后发现 C-Jun 可能在曲妥珠单抗耐药逆转中起关键作用。这一过程可能涉及 JUN 对 DUSP1 的转录激活，从而调节 DUSP1 相关信号通路。结论：本研究表明，紫杉醇可能通过 JUN 逆转曲妥珠单抗耐药，而 JUN 可能反过来调节 DUSP1 和 DUSP1 相关信号通路。