Background: Chemotherapy resistance is a barrier to effective cancer prognoses. Cisplatin (CDDP) resistance is a major challenge for esophageal cancer (EC) therapy. A deeper understanding of the fundamental mechanisms of cisplatin resistance and improved targeting strategies are required in clinical settings. This study was performed to identify and characterize a marker of cisplatin resistance in EC cells./nMethod: KYSE140 and Eca-109 cells were subjected to escalating concentrations of cisplatin, resulting in the development of cisplatin-resistant KYSE140/CDDP and Eca-109/CDDP cell lines, respectively. RNA Sequencing (RNA-seq) was utilized to screen for the genes exhibiting differential expression between cisplatin-resistant and parental cells. Reverse transcription quantitative PCR was conducted to assess gene expression, and western blotting was employed to analyze protein levels. A sphere-formation assay was performed to validate tumor cell stemness. Cell counting kit-8 (CCK-8) experiments were conducted to confirm the sensitivity of cells to cisplatin. We examined the relationship between target genes and the clinicopathological features of patients with EC. Furthermore, the expression of target genes in EC tissues was evaluated via western blotting and fluorescence probe in situ hybridization (FISH)./nResults: KYNU was upregulated in cisplatin-resistant EC cells (KYSE140/CDDP and Eca-109/CDDP cells) and in EC tissues compared to that in the respective parental cell lines (KYSE140 and Eca-109 cells) and non-carcinoma tissues. Downregulation of KYNU increased cell sensitivity to cisplatin and suppressed tumor stemness, whereas abnormal KYNU expression had the opposite effect. KYNU expression was correlated with the expression of tumor stemness-associated factors (SOX2, Nanog, and OCT4) and the tumor size./nConclusions: KYNU may promote drug resistance in EC by regulating cancer stemness, and could serve as a biomarker and therapeutic target for EC.

中文翻译：

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KYNU 表达促进食管癌顺铂耐药

背景：化疗耐药是有效癌症预后的障碍。顺铂（CDDP）耐药性是食管癌（EC）治疗的主要挑战。临床环境中需要更深入地了解顺铂耐药的基本机制并改进靶向策略。本研究的目的是鉴定和表征 EC 细胞中顺铂耐药性的标志物。/n方法： KYSE140 和 Eca-109 细胞接受逐渐浓度的顺铂处理，导致出现顺铂耐药性 KYSE140/CDDP 和 Eca-109分别为/CDDP细胞系。 RNA测序（RNA-seq）用于筛选顺铂耐药细胞和亲本细胞之间表现出差异表达的基因。进行逆转录定量PCR来评估基因表达，并采用蛋白质印迹来分析蛋白质水平。进行球体形成测定以验证肿瘤细胞干性。进行细胞计数试剂盒8（CCK-8）实验以确认细胞对顺铂的敏感性。我们研究了靶基因与 EC 患者临床病理特征之间的关系。此外，通过蛋白质印迹和荧光探针原位杂交（FISH）评估EC组织中靶基因的表达。/n结果： KYNU在顺铂耐药EC细胞（KYSE140/CDDP和Eca-109/CDDP细胞）中上调以及在 EC 组织中与各自亲本细胞系（KYSE140 和 Eca-109 细胞）和非癌组织中的比较。 KYNU 的下调增加了细胞对顺铂的敏感性并抑制了肿瘤干性，而异常的 KYNU 表达则具有相反的作用。 KYNU 表达与肿瘤干性相关因子（SOX2、Nanog 和 OCT4）的表达以及肿瘤大小相关。/n结论： KYNU 可能通过调节癌症干性促进 EC 耐药，并可作为生物标志物和治疗药物EC 的目标。