食管癌（EC）的发病率仍在全球范围内逐渐上升，其复发和五年生存率保持不变，这归因于化疗耐药的发展。顺铂是EC主要用于化疗的药物之一，耐药是一个主要麻烦。本研究揭示了miRNA失调和其与失调mRNA之间的反向关系，引导了通向表现为EC中顺铂耐药的途径。建立了一个顺铂耐药版本的EC细胞系，并通过与母细胞系的比较分析，使用NGS鉴定miRNA和mRNA水平的失调。使用Cytoscape进行蛋白质相互作用网络分析，随后进行Funrich通路分析。此外，使用qRT-PCR验证了选择性显著miRNA。使用Ingenuity Pathway Analysis（IPA）工具进行miRNA-mRNA集成分析。各种已建立的耐药标志物的表达支持成功建立顺铂耐药性细胞系。整个细胞的小RNA测序和转录组测序分别鉴定了261个miRNA和1892个基因的显著差异表达( DE )。通路分析显示出EMT信号的富集，该信号受NOTCH、mTOR、TNF受体和PI3K介导的AKT信号通路支持，这在耐药细胞中得到了证实。切实验证了qRT-PCR中miR-10a-5p、miR-618、miR-99a-5p和miR-935的上调及miR-335-3p、miR-205-5p、miR-944、miR-130a-3p及miR-429的下调。随后的IPA分析中的通路分析表明，这些miRNA的失调及其靶基因可能通过p53信号转导、异物代谢和NRF2介导的氧化应激 在发展和调节化疗耐药方面发挥重要作用。本研究认为，在体外指导调节、获取和维持食管癌耐药时，miRNA和mRNA之间的相互作用是一个重要的方面和发生。© 2023年作者，授权Springer-Verlag GmbH Deutschland独家使用，属于Springer Nature的一部分。

Esophageal cancer (EC) incidence remains to be on a global rise supported by an unchanged recurrence and 5-year survival rate owing to the development of chemoresistance. Resistance to cisplatin, one of the majorly used chemotherapeutic drugs in EC, is a major nuisance. This study sheds light on miRNA dysregulation and its inverse relation with dysregulated mRNAs to guide pathways into the manifestation of cisplatin resistance in EC. A cisplatin-resistant version of an EC cell line was established and comparative profiling by NGS with the parental cell line was employed to identify dysregulation in miRNA and mRNA levels. Protein-protein interaction network analysis was done using Cytoscape, followed by Funrich pathway analysis. Furthermore, selective significant miRNAs were validated using qRT-PCR. miRNA-mRNA integrated analysis was carried out using the Ingenuity Pathway Analysis (IPA) tool. Expression of various established resistance markers supported the successful establishment of cisplatin-resistant cell line. Whole-cell small RNA sequencing and transcriptome sequencing identified 261 miRNAs and 1892 genes to be significantly differentially expressed (DE), respectively. Pathway analysis indicated enrichment of EMT signaling, supported by NOTCH, mTOR, TNF receptor, and PI3K-mediated AKT signaling pathways, in chemoresistant cells. Validation by qRT-PCR confirmed upregulation of miR-10a-5p, miR-618, miR-99a-5p, and miR-935 and downregulation of miR-335-3p, miR-205-5p, miR-944, miR-130a-3p, and miR-429 in resistant cells. Pathway analysis that followed IPA analysis indicated that the dysregulation of these miRNAs and their target genes may be instrumental in the development and regulation of chemoresistance via p53 signaling, xenobiotic metabolism, and NRF2-mediated oxidative stress. This study concludes the interplay between miRNA and mRNA as an important aspect and occurrence in guiding the regulation, acquisition, and maintenance of chemoresistance in esophageal cancer in vitro.© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.