Integrated analysis of DNA methylation and mRNA expression profiling reveals candidate genes associated with cisplatin resistance in non-small cell lung cancer
| العنوان: | Integrated analysis of DNA methylation and mRNA expression profiling reveals candidate genes associated with cisplatin resistance in non-small cell lung cancer |
|---|---|
| المؤلفون: | Xiao-Xia Lu, Jiandong Tong, Jing-Zi Wang, Xiao-Xiang Guan, Longbang Chen, Zhu Wang, You-Wei Zhang, Yun Zheng |
| المصدر: | Epigenetics. 9:896-909 |
| بيانات النشر: | Informa UK Limited, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Antimetabolites, Antineoplastic, Cancer Research, Candidate gene, Lung Neoplasms, endocrine system diseases, Antineoplastic Agents, Apoptosis, Cell Cycle Proteins, Biology, Decitabine, GPI-Linked Proteins, Hydroxamic Acids, Epigenesis, Genetic, Carcinoma, Non-Small-Cell Lung, Cell Line, Tumor, medicine, Humans, RNA, Messenger, Molecular Biology, Cell Proliferation, Cisplatin, Cell growth, Gene Expression Profiling, Cell Cycle Checkpoints, Methylation, DNA Methylation, Cell cycle, Molecular biology, Histone Deacetylase Inhibitors, Gene expression profiling, Trichostatin A, Drug Resistance, Neoplasm, DNA methylation, Azacitidine, Cancer research, Research Paper, medicine.drug |
| الوصف: | DNA methylation plays a critical role during the development of acquired chemoresistance. The aim of this study was to identify candidate DNA methylation drivers of cisplatin (DDP) resistance in non-small cell lung cancer (NSCLC). The A549/DDP cell line was established by continuous exposure of A549 cells to increasing concentrations of DDP. Gene expression and methylation profiling were determined by high-throughput microarrays. Relationship of methylation status and DDP response was validated in primary tumor cell culture and the Cancer Genome Atlas (TCGA) samples. Cell proliferation, apoptosis, cell cycle, and response to DDP were determined in vitro and in vivo. A total of 372 genes showed hypermethylation and downregulation in A549/DDP cells, and these genes were involved in most fundamental biological processes. Ten candidate genes (S100P, GDA, WISP2, LOXL1, TIMP4, ICAM1, CLMP, HSP8, GAS1, BMP2) were selected, and exhibited varying degrees of association with DDP resistance. Low dose combination of 5-aza-2'-deoxycytidine (5-Aza-dC) and trichostatin A (TSA) reversed drug resistance of A549/DDP cells in vitro and in vivo, along with demethylation and restoration of expression of candidate genes (GAS1, TIMP4, ICAM1 and WISP2). Forced expression of GAS1 in A549/DDP cells by gene transfection contributed to increased sensitivity to DDP, proliferation inhibition, cell cycle arrest, apoptosis enhancement, and in vivo growth retardation. Together, our study demonstrated that a panel of candidate genes downregulated by DNA methylation induced DDP resistance in NSCLC, and showed that epigenetic therapy resensitized cells to DDP. |
| تدمد: | 1559-2308 1559-2294 |
| DOI: | 10.4161/epi.28601 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::db7c69ccdc0d19aeb843df07b7d4f773 https://doi.org/10.4161/epi.28601 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....db7c69ccdc0d19aeb843df07b7d4f773 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15592308 15592294 |
|---|---|
| DOI: | 10.4161/epi.28601 |