研究动态
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EIF4A3介导的致癌circRNA hsa_circ_0001165通过miR-381-3p/TNS3途径促进食管鳞状细胞癌的进展。

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

发表日期:2024 Oct 09
作者: Xun Zhang, Yan Bian, Qiuxin Li, Chuting Yu, Ye Gao, Bo Tian, Wenqiang Xia, Wei Wang, Lei Xin, Han Lin, Luowei Wang
来源: CELL BIOLOGY AND TOXICOLOGY

摘要:

食管鳞状细胞癌(ESCC)由于其预后不良且缺乏有效的治疗靶点,仍然是一个重大的临床挑战。环状 RNA (circRNA) 在癌症进展中至关重要。在这项研究中,采用高通量测序对食管鳞癌组织进行分析,发现hsa_circ_0001165在食管鳞癌肿瘤样本和细胞系中均显着升高,其表达与患者的TNM分期呈正相关。 hsa_circ_0001165 的敲低导致体外食管鳞癌细胞的恶性生物学行为减少,并且还抑制了体内肿瘤的生长。机制实验分析发现hsa_circ_0001165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测定(包括双荧光素酶报告基因、RNA 免疫沉淀和 RNA 下拉)增加张力蛋白-3 (TNS3) 的表达。 ESCC组织中miR-381-3p表达下调,ESCC细胞增殖、侵袭和迁移受到抑制。 hsa_circ_0001165 表达上调可调节 miR-381-3p/TNS3 轴并促进 ESCC 的侵袭性表型。 Hsa_circ_0001165 被认为是 ESCC 的令人鼓舞的生物标志物和潜在治疗靶点,为诊断和治疗方法提供了创新选择。© 2024。作者。
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.© 2024. The Author(s).