LncRNA NONHSAT227443.1 通过靶向 MRTFB 激活 PI3K/AKT 信号传导,赋予食管鳞状细胞癌化疗耐药性。
LncRNA NONHSAT227443.1 Confers Esophageal Squamous Cell Carcinoma Chemotherapy Resistance by Activating PI3K/AKT Signaling via Targeting MRTFB.
发表日期:2024
作者:
Yuchen Wang, Yingying Wang, Jinze Zhang, Zhihua Shi, Junfeng Liu
来源:
Cell Death & Disease
摘要:
由于治疗选择有限和预后不良,特别是在晚期,食管癌面临着巨大的挑战。失调的长非编码 RNA (lncRNA) 与癌症进展和治疗耐药有关。本研究探讨了通过 lncRNA-seq 鉴定的失调 lncRNA NONHSAT227443.1 及其下游靶基因 MRTFB 在食管鳞状细胞癌 (ESCC) 中的作用。通过 lncRNA-seq 在具有不同化疗反应的食管癌组织中鉴定了失调的 lncRNA。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 的调控相互作用。通过细胞活力、细胞增殖和流式细胞术分析等功能分析来全面研究NONHSAT227443.1及其下游分子对ESCC的影响。NONHSAT227443.1在紫杉醇联合铂类化疗无反应者和食管癌中显着过表达细胞系。化疗暴露导致 NONHSAT227443.1 表达减少。 NONHSAT227443.1 负向调节 MRTFB 表达,它们的联合失调与癌症活性增加、增殖和抑制细胞凋亡相关。 MRTFB 表达减少与 PI3K/AKT 通路激活相关。我们的研究深入了解了 NONHSAT227443.1 和 MRTFB 在食管癌中的作用,有助于侵袭性特征和治疗抵抗。 NONHSAT227443.1 和 MRTFB 可能作为潜在的治疗靶点,以增强无反应病例对紫杉醇加铂类化疗的反应。
Esophageal cancer presents significant challenges due to limited treatment options and poor prognosis, particularly in advanced stages. Dysregulated long non-coding RNAs (lncRNAs) are implicated in cancer progression and treatment resistance. This study investigated the roles of dysregulated lncRNA NONHSAT227443.1, identified through lncRNA-seq, and its downstream target gene MRTFB in esophageal squamous cell carcinoma (ESCC).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.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.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.