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

EIF4A3-mediated oncogenic circRNA hsa_circ_0001165 advances esophageal squamous cell carcinoma progression through the miR-381-3p/TNS3 pathway.

机构信息

Department of Gastroenterology, Changhai Hospital, Naval Medical University, Shanghai, 200433, China.

Digestive Endoscopic Center, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.

出版信息

Cell Biol Toxicol. 2024 Oct 9;40(1):84. doi: 10.1007/s10565-024-09927-9.

Abstract

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.

摘要

食管鳞状细胞癌 (ESCC) 由于预后不良和有效治疗靶点稀缺,仍然是一个主要的临床挑战。环状 RNA (circRNA) 在癌症进展中起着至关重要的作用。在这项研究中,高通量测序用于分析 ESCC 组织,结果表明 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。敲低 hsa_circ_0001165 导致 ESCC 细胞体外恶性生物学行为降低,并抑制体内肿瘤生长。机制实验分析发现,hsa_circ_0001165 的表达被真核翻译起始因子 4A3 (EIF4A3) 正向增强。hsa_circ_0001165 作为 miR-381-3p 的 miRNA 海绵,通过一系列相关机制实验,包括双荧光素酶报告基因、RNA 免疫沉淀和 RNA 下拉实验,增加了张力蛋白 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,并促进了 ESCC 的侵袭表型。hsa_circ_0001165 被认为是 ESCC 有希望的生物标志物和潜在治疗靶点,为诊断和治疗方法提供了新的选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7a8/11481643/dea034f4ec0a/10565_2024_9927_Fig1_HTML.jpg

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