TPX2通过与LINC00894形成ceRNA促进乳头状肾细胞癌的进展。

IF 2.1 4区 医学 Q3 GENETICS & HEREDITY
Zhenshan Ding, Wenwei Ying, Ye Yan, Ying Zhao, Cheng Liu, Lulin Ma
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引用次数: 0

摘要

目的:乳头状肾细胞癌(pRCC),尤其是2型,预后不良。本研究旨在确定pRCC进展的分子机制,并探索改善患者预后的潜在治疗靶点。方法:对2型pRCC患者肿瘤标本中TPX2的表达进行分析。体外实验研究TPX2和LINC00894敲低和过表达对Caki-2和ACHN细胞增殖和迁移的影响。组织微阵列免疫组织化学分析评估TPX2表达与2型pRCC患者临床病理特征之间的关系。结果:TPX2表达升高与2型pRCC患者预后不良显著相关,是影响总生存的独立危险因素。在Caki-2和ACHN细胞中,TPX2的表达下调可显著降低细胞的增殖和迁移。此外,LINC00894在2型pRCC中高表达,与不良预后相关。在机制上,miR-660-5p靶向TPX2 3' UTR,促进TPX2降解,而LINC00894竞争性地结合miR-660-5p,保护TPX2免受mirna介导的降解,并发挥促癌作用。免疫组化分析显示TPX2表达与肿瘤血栓体积、肿瘤直径、病理TNM分期、Fuhrman分级等临床病理特征有显著相关性。结论:本研究强调了TPX2在2型pRCC进展中的关键作用,并强调了其作为预后生物标志物和治疗靶点的潜力。TPX2/LINC00894/miR-660-5p调控轴为驱动pRCC的分子机制提供了新的见解,并为改善患者预后提供了有希望的途径。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
TPX2 promotes papillary renal cell carcinoma progression by forming a ceRNA with LINC00894.

Purpose: Papillary renal cell carcinoma (pRCC), particularly type 2, is associated with a poor prognosis. This study aimed to identify molecular mechanisms underlying pRCC progression and explore potential therapeutic targets to improve patient outcomes.

Methods: TPX2 expression was analyzed in tumor samples from patients with type 2 pRCC. In vitro experiments were conducted to assess the effects of TPX2 and LINC00894 knockdown and overexpression on the proliferation and migration of Caki-2 and ACHN cells. Immunohistochemical analysis of tissue microarrays was performed to evaluate the associations between TPX2 expression and clinicopathological characteristics in type 2 pRCC patients.

Results: Elevated TPX2 expression was significantly associated with a worse prognosis in type 2 pRCC patients and served as an independent risk factor for overall survival. Knockdown of TPX2 in Caki-2 and ACHN cells significantly reduced cell proliferation and migration. Additionally, LINC00894 was highly expressed in type 2 pRCC and correlated with poor prognosis. Mechanistically, miR-660-5p targeted the TPX2 3' UTR, promoting TPX2 degradation, while LINC00894 competitively bound to miR-660-5p, protecting TPX2 from miRNA-mediated degradation and exerting a pro-oncogenic effect. Immunohistochemical analysis revealed significant correlations between TPX2 expression and clinicopathological features, including tumor thrombus volume, tumor diameter, pathological TNM stage, and Fuhrman grade.

Conclusion: This study underscores the critical role of TPX2 in type 2 pRCC progression and highlights its potential as a prognostic biomarker and therapeutic target. The TPX2/LINC00894/miR-660-5p regulatory axis provides novel insights into the molecular mechanisms driving pRCC and offers a promising avenue for improving patient prognosis.

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来源期刊
BMC Medical Genomics
BMC Medical Genomics 医学-遗传学
CiteScore
3.90
自引率
0.00%
发文量
243
审稿时长
3.5 months
期刊介绍: BMC Medical Genomics is an open access journal publishing original peer-reviewed research articles in all aspects of functional genomics, genome structure, genome-scale population genetics, epigenomics, proteomics, systems analysis, and pharmacogenomics in relation to human health and disease.
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