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长链非编码RNA LUCAT1通过靶向miR-141-3p作为胆管癌的预后生物标志物:临床和功能见解

LncRNA LUCAT1 as a prognostic biomarker in cholangiocarcinoma through targeting miR-141-3p: clinical and functional insights.

作者信息

An Yuxin, Chen Qing, Zhou Shanshan, Ying Chengcheng, Long Guanbao, Hu Zouxiao, Sun Jiangyang, Zhang Niu

机构信息

School of Medicine, Jiangsu University, Zhenjiang, 212013, China.

Orthopedic of Department, Shenzhen Third People's Hospital, Shenzhen, Guangdong Province, 518112, China.

出版信息

Hereditas. 2025 Jul 26;162(1):143. doi: 10.1186/s41065-025-00512-6.

Abstract

BACKGROUND

Cholangiocarcinoma (CHOL) has a poor prognosis due to its asymptomatic progression, challenges in early detection, and limited treatment options. The lncRNA LUCAT1 is highly expressed in several cancers, including lung, gastric, ovarian, and osteosarcoma tissues.

AIM

This study investigates the potential of LUCAT1 as a diagnostic and prognostic biomarker for CHOL.

MATERIALS AND METHODS

In this study, we collected tumor tissues and adjacent tumor healthy tissues from 83 CHOL patients. LUCAT1 expression was quantified in CHOL tissues and cell lines via RT-qPCR. Diagnostic and prognostic significance was assessed through ROC curves, Kaplan-Meier survival analysis, and Cox regression models. The biological effects of LUCAT1 on cell proliferation and migration were examined using QBC939 and HuCCT1 cells with transfection assays. The regulatory interaction between LUCAT1 and miR-141-3p was validated using a dual-luciferase reporter assay.

RESULTS

Elevated expression of LUCAT1 was observed in CHOL tumor tissues and human cholangiocarcinoma cells, correlating with tumor size, CA-19-9 levels, and TNM stage. The ROC curve, with an AUC of 0.908 (p < 0.001), effectively distinguished CHOL tumor tissues from adjacent non-tumor tissues. And its sensitivity and specificity in distinguishing CHOL tissues from normal tissues were 88.5% and 89.2%, respectively. Survival analyses linked LUCAT1 overexpression to poorer patient outcomes. Silencing LUCAT1 impaired the proliferation and migration of QBC939 and HuCCT1 cells. Dual-luciferase assay confirmed the regulatory relationship between miR-141-3p and LUCAT1. Inhibition of miR-141-3p reversed the effect of LUCAT1 on the proliferation and migration of QBC939 and HuCCT1 cells.

CONCLUSION

LUCAT1 demonstrates significant diagnostic and prognostic potential and could serve as a novel biomarker for CHOL.

摘要

背景

胆管癌(CHOL)因其无症状进展、早期检测困难以及治疗选择有限,预后较差。长链非编码RNA LUCAT1在包括肺癌、胃癌、卵巢癌和骨肉瘤组织在内的多种癌症中高表达。

目的

本研究探讨LUCAT1作为胆管癌诊断和预后生物标志物的潜力。

材料与方法

在本研究中,我们收集了83例胆管癌患者的肿瘤组织及相邻的肿瘤旁健康组织。通过逆转录定量聚合酶链反应(RT-qPCR)对胆管癌组织和细胞系中的LUCAT1表达进行定量。通过受试者工作特征(ROC)曲线、Kaplan-Meier生存分析和Cox回归模型评估其诊断和预后意义。使用QBC939和HuCCT1细胞进行转染实验,检测LUCAT1对细胞增殖和迁移的生物学作用。使用双荧光素酶报告基因检测法验证LUCAT1与miR-141-3p之间的调控相互作用。

结果

在胆管癌肿瘤组织和人胆管癌细胞中观察到LUCAT1表达升高,其与肿瘤大小、CA-19-9水平和TNM分期相关。ROC曲线下面积(AUC)为0.908(p<0.001),能有效区分胆管癌肿瘤组织与相邻的非肿瘤组织。其区分胆管癌组织与正常组织的敏感性和特异性分别为88.5%和89.2%。生存分析表明LUCAT1过表达与患者较差的预后相关。沉默LUCAT1会损害QBC939和HuCCT1细胞的增殖和迁移。双荧光素酶检测证实了miR-141-3p与LUCAT1之间的调控关系。抑制miR-141-3p可逆转LUCAT1对QBC939和HuCCT1细胞增殖和迁移的影响。

结论

LUCAT1具有显著的诊断和预后潜力,可作为胆管癌的新型生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8162/12297753/e84684192e63/41065_2025_512_Fig1_HTML.jpg

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