原发性肝癌是全球癌症相关死亡的第三大原因，并且该疾病与血栓形成的高发生率相关。研究表明组织因子途径抑制剂 (TFPI) 在癌症发展中发挥作用。我们的目的是研究其在肝细胞癌（HCC）中的表达、临床作用和微小RNA（miRNA）的调节。通过网络分析工具使用公开数据集对TFPI和miRNA表达进行临床分析。从目标预测程序中选择靶向 TFPIα 3'非翻译区 (UTR) 的 miRNA 模拟物，并通过荧光素酶报告基因测定进行验证。体外分析HCC细胞系中miRNA过表达对TFPI表达以及细胞增殖和凋亡的影响。与正常组织相比，HCC肿瘤中TFPI表达显着升高。低 TFPI 肿瘤表达与更好的生存概率相关。从目标预测程序中选择了四个候选 miRNA。 miR-7-5p 和 miR-1236-3p 在 HepG2 和 Huh7 细胞中得到验证，可降低过度表达后的 TFPI mRNA 和蛋白质水平。此外，miR-7-5p 和 miR-1236-3p 降低了 TFPIα-3'UTR 控制的荧光素酶活性。这两种经过验证的 miRNA 可抑制 HepG2 细胞的增殖，在 HCC 中具有临床意义。与正常组织相比，HCC 肿瘤中的 TFPI 升高，并且 TFPI 高表达与 HCC 患者的不良预后相关。 miR-7-5p 和 miR-1236-3p 被鉴定为体外 TFPI 的新型调节因子。版权所有 © 2024 作者。由爱思唯尔有限公司出版。保留所有权利。

Primary liver cancer is the third leading cause of cancer related deaths worldwide, and the disease is associated with high incidence rate of thrombosis. Studies indicate that Tissue Factor Pathway Inhibitor (TFPI) plays a role in cancer development. We aimed to study its expression, clinical role and regulation by micro RNAs (miRNAs) in hepatocellular carcinoma (HCC).Publically available datasets were used for clinical analysis of TFPI and miRNAs expression by web analysis tools. miRNA mimics targeting TFPIα 3'untranslated region (UTR) were selected from target prediction programs and verified by luciferase reporter assay. In vitro effects of miRNAs overexpression in HCC cell lines on TFPI expression and cell proliferation and apoptosis were analysed.TFPI expression was significantly increased in HCC tumours compared to normal tissue. Low TFPI tumour expression was associated with better survival probability. Four candidate miRNAs were selected from the target prediction programs. miR-7-5p and miR-1236-3p were validated in HepG2 and Huh7 cells to reduce TFPI mRNA and protein levels following overexpression. Furthermore, miR-7-5p and miR-1236-3p reduced TFPIα-3'UTR-controlled luciferase activity. The two validated miRNAs inhibited proliferation of HepG2 cells, and had clinical significance in HCC.TFPI was increased in HCC tumours compared to normal tissue and high TFPI expression was associated with an unfavorable outcome in HCC patients. miR-7-5p and miR-1236-3p were identified as novel regulators of TFPI in vitro.Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.