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Mir-1301-3p对FHL1的抑制促进子宫体子宫内膜癌细胞增殖和迁移:一项预后分析

FHL1 Inhibition by Mir-1301-3p Promotes Uterine Corpus Endometrial Carcinoma Cell Proliferation and Migration: A Prognostic Insight.

作者信息

Zhu Mengna, Chen Buze, Miao Lu, Sun Jieyun, Li Yuanyuan, Zhang Pei, Lu Xiaoyuan

机构信息

Graduate School, Xuzhou Medical University, Xuzhou, 221000, Jiangsu, China.

Department of Gynecology, Xinyi Hospital of Traditional Chinese Medicine, Xinyi, 221499, Jiangsu, China.

出版信息

Curr Med Chem. 2024 Dec 11. doi: 10.2174/0109298673341564241031063856.

DOI:10.2174/0109298673341564241031063856
PMID:39665305
Abstract

BACKGROUND

The impact of microRNA-1301-3p (miR-1301-3p) on various cancer subtypes is noteworthy. However, its specific role within the framework of uterine corpus endometrial carcinoma (UCEC) is yet to be clearly defined.

OBJECTIVE

The objective of this research was to investigate and clarify the function of miR-1301-3p in relation to UCEC.

METHODS

Sample data for our study were sourced from The Cancer Genome Atlas (TCGA). Using various statistical techniques, we assessed the potential of miR-1301-3p as a diagnostic and prognostic indicator, as well as its association with clinical characteristics. Additionally, we conducted an analysis of the genes targeted by miR-1301-3p. The expression levels of miR-1301-3p in uterine corpus endometrial carcinoma (UCEC) cell lines were determined by quantitative real-time PCR (qRT-PCR). Cellular viability and migratory capacity were measured using the CCK8 assay and Transwell migration assays, respectively. Moreover, the expression levels of genes and proteins targeted by miR-1301-3p were identified through dual-luciferase reporter gene assays and Western blot analysis.

RESULTS

Expression patterns of miR-1301-3p varied across cancer subtypes, which were significantly linked to specific histological classifications, achieving statistical significance (p < 0.001). In UCEC, higher miR-1301-3p levels correlated with reduced overall survival (p = 0.012) and progression-free survival (p = 0.016), and it emerged as an independent prognostic marker for UCEC. A comparative analysis revealed significantly higher miR-1301-3p levels in UCEC cell lines compared to normal endometrial epithelial cells. Four and a half LIM domains 1 (FHL1) exhibited a negative correlation with miR-1301-3p levels within UCEC tissue samples. miR-1301-3p was shown to promote UCEC cell proliferation and migration through its binding to the 3'-untranslated region (UTR) of the FHL1 gene, thereby repressing FHL1 expression. Additionally, augmenting FHL1 levels was observed to counteract the enhancing impact of miR-1301-3p on UCEC cells.

CONCLUSION

miR-1301-3p regulates the proliferation and migration of UCEC cells by interacting with the FHL1 gene. miR-1301-3p may serve as a promising prognostic biomarker in UCEC.

摘要

背景

微小RNA-1301-3p(miR-1301-3p)对多种癌症亚型的影响值得关注。然而,其在子宫内膜癌(UCEC)框架内的具体作用尚待明确。

目的

本研究旨在探究并阐明miR-1301-3p在UCEC中的功能。

方法

本研究的样本数据来自癌症基因组图谱(TCGA)。我们运用多种统计技术评估了miR-1301-3p作为诊断和预后指标的潜力,以及它与临床特征的关联。此外,我们对miR-1301-3p的靶基因进行了分析。通过定量实时聚合酶链反应(qRT-PCR)测定miR-1301-3p在子宫内膜癌细胞系中的表达水平。分别使用CCK8法和Transwell迁移试验检测细胞活力和迁移能力。此外,通过双荧光素酶报告基因试验和蛋白质免疫印迹分析确定miR-1301-3p靶基因的基因和蛋白表达水平。

结果

miR-1301-3p的表达模式在不同癌症亚型中有所不同,与特定的组织学分类显著相关,具有统计学意义(p < 0.001)。在UCEC中,较高的miR-1301-3p水平与总生存期缩短(p = 0.012)和无进展生存期缩短(p = 0.016)相关,并且它成为UCEC的独立预后标志物。一项比较分析显示,与正常子宫内膜上皮细胞相比,UCEC细胞系中的miR-1301-3p水平显著更高。在UCEC组织样本中,四又二分之一LIM结构域蛋白1(FHL1)与miR-1301-3p水平呈负相关。结果表明,miR-1301-3p通过与FHL1基因的3'非翻译区(UTR)结合来促进UCEC细胞增殖和迁移,从而抑制FHL1表达。此外,观察到增加FHL1水平可抵消miR-1301-3p对UCEC细胞的增强作用。

结论

miR-1301-3p通过与FHL1基因相互作用调节UCEC细胞的增殖和迁移。miR-1301-3p可能是UCEC中有前景的预后生物标志物。

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