Advanced bioinformatic analysis and pathway prediction of NSCLC cells upon cisplatin resistance.
Advanced bioinformatic analysis and pathway prediction of NSCLC cells upon cisplatin resistance.
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DOI：
10.1038/s41598-021-85930-y
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发表时间：
2021-03-22
影响因子：
4.6
通讯作者：
Mattheolabakis G
中科院分区：
文献类型：
--
作者：
Hossian AKMN;Zahra FT;Poudel S;Abshire CF;Polk P;Garai J;Zabaleta J;Mikelis CM;Mattheolabakis G
本研究旨在利用先进的生物信息学软件，确定 A549 肺癌 (LC) 细胞中顺铂（顺二氨二氯铂 (II)；CDDP）耐药性发展的相关途径。我们通过与药物长时间孵育来开发 CDDP 抗性 A549 (A549/DDP) 细胞，并对 RNA 提取物进行 RNA 测序，以确定 A549/DDP 和 A549 细胞之间的差异 mRNA 和 miRNA 表达。我们使用 Ingenuity Pathway Analysis (IPA; QIAGEN) 软件分析了基因失调。先前的研究依赖于通路失调基因的聚类作为通路活性的指示，与此相反，我们利用 IPA 软件根据基因失调水平动态评估通路活性。我们预测了 15 条对化学耐药性有显着影响的途径，其中一些途径之前尚未被详细报道或详细分析。其中包括PKR信号通路、胆固醇生物合成和TEC信号通路，以及PIK3R3、miR-34c-5p和MDM2等基因。我们还提供了仅存在于 A549/DDP 细胞中的 SNP 和插入缺失的初步分析。这项研究的结果提供了新的潜在机制和分子靶点，可以在未来的研究中进行探索，并有助于提高对化疗耐药表型的理解。
This study aims to identify pathway involvement in the development of cisplatin (cis-diamminedichloroplatinum (II); CDDP) resistance in A549 lung cancer (LC) cells by utilizing advanced bioinformatics software. We developed CDDP-resistant A549 (A549/DDP) cells through prolonged incubation with the drug and performed RNA-seq on RNA extracts to determine differential mRNA and miRNA expression between A549/DDP and A549 cells. We analyzed the gene dysregulation with Ingenuity Pathway Analysis (IPA; QIAGEN) software. In contrast to prior research, which relied on the clustering of dysregulated genes to pathways as an indication of pathway activity, we utilized the IPA software for the dynamic evaluation of pathway activity depending on the gene dysregulation levels. We predicted 15 pathways significantly contributing to the chemoresistance, with several of them to have not been previously reported or analyzed in detail. Among them, the PKR signaling, cholesterol biosynthesis, and TEC signaling pathways are included, as well as genes, such as PIK3R3, miR-34c-5p, and MDM2, among others. We also provide a preliminary analysis of SNPs and indels, present exclusively in A549/DDP cells. This study's results provide novel potential mechanisms and molecular targets that can be explored in future studies and assist in improving the understanding of the chemoresistance phenotype.
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DOI：
10.3881/j.issn.1000-503x.2015.05.005
发表时间：
2015-10-01
期刊：
Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae
影响因子：
--
作者：
Chen, Dian-dian;Feng, Lin-chun;Wang, Ya-di
通讯作者：
Wang, Ya-di
影响因子：
3.7
作者：
Barr MP;Gray SG;Hoffmann AC;Hilger RA;Thomale J;O'Flaherty JD;Fennell DA;Richard D;O'Leary JJ;O'Byrne KJ
通讯作者：
O'Byrne KJ
影响因子：
4.1
作者：
da Silva Junior IA;Stone SC;Rossetti RM;Jancar S;Lepique AP
通讯作者：
Lepique AP
影响因子：
1.2
作者：
Cingolani, Pablo;Platts, Adrian;Ruden, Douglas M.
通讯作者：
Ruden, Douglas M.
影响因子：
13.6
作者：
Bajwa, Amandeep;Rosin, Diane L.;Okusa, Mark D.
通讯作者：
Okusa, Mark D.