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