EIF4A3 介导的致癌 circRNA hsa_circ_0001165 通过 miR-381-3p/TNS3 通路促进食管鳞状细胞癌的进展。

IF 5.3 2区 医学 Q2 CELL BIOLOGY Cell Biology and Toxicology Pub Date : 2024-10-09 DOI:10.1007/s10565-024-09927-9
Xun Zhang, Yan Bian, Qiuxin Li, Chuting Yu, Ye Gao, Bo Tian, Wenqiang Xia, Wei Wang, Lei Xin, Han Lin, Luowei Wang
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引用次数: 0

摘要

食管鳞状细胞癌(ESCC)预后不良,且缺乏有效的治疗靶点,因此仍是一项重大的临床挑战。环状 RNA(circRNA)在癌症进展中至关重要。本研究采用高通量测序技术对 ESCC 组织进行了分析,结果显示 hsa_circ_0001165 在 ESCC 肿瘤样本和细胞系中均显著升高,其表达与患者的 TNM 分期呈正相关。敲除 hsa_circ_0001165 会降低 ESCC 细胞在体外的恶性生物学行为,并抑制肿瘤在体内的生长。机制实验分析发现,真核翻译起始因子4A3(EIF4A3)可正向增强hsa_circ_0001165的表达。通过双荧光素酶报告基因、RNA免疫沉淀和RNA-pulldown等一系列相关机制实验,Hsa_circ_0001165可作为miRNA的海绵,增加tensin-3(TNS3)的表达。在 ESCC 组织中观察到 miR-381-3p 表达下调,ESCC 的细胞增殖、侵袭和迁移受到抑制。hsa_circ_0001165的上调表达调节了miR-381-3p/TNS3轴,促进了ESCC侵袭性表型的形成。Hsa_circ_0001165被认为是一种令人鼓舞的生物标志物和ESCC的潜在治疗靶点,为诊断和治疗方法提供了创新选择。
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EIF4A3-mediated oncogenic circRNA hsa_circ_0001165 advances esophageal squamous cell carcinoma progression through the miR-381-3p/TNS3 pathway.

Esophageal squamous cell carcinoma (ESCC) remains a major clinical challenge due to its poor prognosis and the scarcity effective therapeutic targets. Circular RNAs (circRNAs) are crucial in cancer progression. In this study, high-throughput sequencing was employed to profile ESCC tissues, revealing that hsa_circ_0001165 is notably elevated in both ESCC tumor samples and cell lines, with its expression is positively associated with patients' TNM staging. Knockdown of hsa_circ_0001165 resulted in reduced malignant biological behavior of ESCC cells in vitro and also inhibited tumor growth in vivo. Mechanism experimental analysis found that hsa_circ_0001165 expression is positively enhanced by eukaryotic translation initiation factor 4A3 (EIF4A3). Hsa_circ_0001165 acts as a miRNA sponge for miR-381-3p, increasing the expression of tensin-3 (TNS3) through a series of related mechanism assays include dual-luciferase reporter gene, RNA Immunoprecipitation and RNA-pulldown. The downregulation in miR-381-3p expression was observed in ESCC tissues, and the cell proliferation, invasion, and migration of ESCC were suppressed. The upregulated expression of hsa_circ_0001165 modulates the miR-381-3p/TNS3 axis and promotes aggressive phenotypes of ESCC. Hsa_circ_0001165 is regarded as a encouraging biomarker and potential therapeutic target for ESCC, presenting innovative options for both diagnostic and treatment approaches.

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来源期刊
Cell Biology and Toxicology
Cell Biology and Toxicology 生物-毒理学
CiteScore
9.90
自引率
4.90%
发文量
101
审稿时长
>12 weeks
期刊介绍: Cell Biology and Toxicology (CBT) is an international journal focused on clinical and translational research with an emphasis on molecular and cell biology, genetic and epigenetic heterogeneity, drug discovery and development, and molecular pharmacology and toxicology. CBT has a disease-specific scope prioritizing publications on gene and protein-based regulation, intracellular signaling pathway dysfunction, cell type-specific function, and systems in biomedicine in drug discovery and development. CBT publishes original articles with outstanding, innovative and significant findings, important reviews on recent research advances and issues of high current interest, opinion articles of leading edge science, and rapid communication or reports, on molecular mechanisms and therapies in diseases.
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