METHODS: Dysregulated lncRNAs were identified through lncRNA-seq in esophageal cancer tissues with varying chemotherapy response. The regulatory interaction of overexpressed NONHSAT227443.1 was assessed using quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting. Functional assays, including cell viability, cell proliferation, and flow cytometry analyses, were performed to comprehensively investigate the influence of NONHSAT227443.1 and its downstream molecules on ESCC.
RESULTS: NONHSAT227443.1 was significantly overexpressed in paclitaxel plus platinum chemotherapy non-responders and esophageal cancer cell lines. Chemotherapy exposure led to diminished NONHSAT227443.1 expression. NONHSAT227443.1 negatively regulated MRTFB expression, and their combined dysregulation correlated with increased cancer activity, proliferation, and suppressed apoptosis. Diminished MRTFB expression was associated with PI3K/AKT pathway activation.
CONCLUSIONS: Our study provides insights into NONHSAT227443.1 and MRTFB roles in esophageal cancer, contributing to aggressive traits and treatment resistance. NONHSAT227443.1 and MRTFB may serve as potential therapeutic targets to enhance the response to paclitaxel plus platinum chemotherapy in non-responsive cases.
方法:通过lncRNA-seq在具有不同化疗反应的食管癌组织中鉴定出失调的lncRNAs。使用定量实时聚合酶链反应(qRT-PCR)和蛋白质印迹评估过表达的NONHSAT227443.1的调节相互作用。功能测定,包括细胞活力,细胞增殖,和流式细胞术分析,进行了全面研究NONHSAT227443.1及其下游分子对ESCC的影响。
结果:NONHSAT227443.1在紫杉醇加铂类化疗无反应者和食管癌细胞系中显著过表达。化疗暴露导致NONHSAT227443.1表达减少。NONHSAT227443.1负调控MRTFB表达,它们的联合失调与癌症活动增加相关,扩散,抑制细胞凋亡。MRTFB表达降低与PI3K/AKT通路激活相关。
结论:我们的研究提供了对NONHSAT227443.1和MRTFB在食管癌中作用的见解,有助于攻击性特征和治疗抗性。NONHSAT227443.1和MRTFB可以作为潜在的治疗靶标,以增强无应答病例对紫杉醇加铂化疗的反应。