KDM4A-AS1 promotes cell proliferation, migration and invasion via the miR-4306/STX6 axis in hepatocellular carcinoma

IF 1.5 4区医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Critical Reviews in Eukaryotic Gene Expression Pub Date : 2024-01-01 DOI:10.1615/critreveukaryotgeneexpr.2024051414

Wei Cao, Yuhan Ren, Ying Liu, Guoshu Cao, Zhen Chen, Fan Wang

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Abstract

Background: As a primary liver malignancy, hepatocellular carcinoma (HCC) is commonly induced by chronic liver disease and cirrhosis. Bioinformatics analysis reveals that long noncoding RNA KDM4A antisense RNA 1 (KDM4A-AS1) may be aberrantly expressed in HCC and its abnormal expression might influence prognosis in patients. Objective: To illustrate the functions and mechanism of KDM4A-AS1 in regulating HCC malignant cell behavior. Methods: KDM4A-AS1, microRNA (miR)-4306 and messenger RNA syntaxin 6 (STX6) expression was examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). HCC cell proliferation, apoptosis, migration, and invasion were measured by colony forming assays, flow cytometry, wound healing and Transwell assays. The interaction between genes was verified by RNA immunoprecipitation and luciferase reporter assays. Western blotting was performed to quantify protein expression of STX6 or apoptotic markers. Results: KDM4A-AS1 was highly expressed in HCC cells and tissues. KDM4A-AS1 knockdown led to enhanced HCC cell apoptosis and suppressed HCC cell proliferation, migration, and invasion. MiR-4306 bound to and negatively regulated STX6. KDM4A-AS1 directly bound to miR-4306 and thus upregulated STX6. STX6 overexpression reversed the inhibitory influence of KDM4A-AS1 depletion on HCC malignant behavior. Conclusions: KDM4A-AS1 promotes HCC cell migration, invasion, and growth by upregulating STX6 via miR-4306.

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KDM4A-AS1 通过 miR-4306/STX6 轴促进肝细胞癌细胞的增殖、迁移和侵袭

背景：肝细胞癌（HCC）是一种原发性肝脏恶性肿瘤，通常由慢性肝病和肝硬化诱发。生物信息学分析发现，长非编码 RNA KDM4A 反义 RNA 1（KDM4A-AS1）可能在 HCC 中异常表达，其异常表达可能影响患者的预后：阐明 KDM4A-AS1 在调控 HCC 恶性细胞行为中的功能和机制：方法：采用反转录定量聚合酶链反应（RT-qPCR）检测KDM4A-AS1、microRNA（miR）-4306和信使RNA句法蛋白6（STX6）的表达。通过集落形成试验、流式细胞术、伤口愈合和 Transwell 试验测定了 HCC 细胞的增殖、凋亡、迁移和侵袭。通过 RNA 免疫沉淀和荧光素酶报告实验验证了基因之间的相互作用。对 STX6 或凋亡标志物的蛋白表达进行了 Western 印迹定量：结果：KDM4A-AS1在HCC细胞和组织中高表达。结果：KDM4A-AS1在HCC细胞和组织中高表达，敲除KDM4A-AS1可增强HCC细胞凋亡，抑制HCC细胞增殖、迁移和侵袭。MiR-4306 与 STX6 结合并对其进行负调控。KDM4A-AS1 直接与 miR-4306 结合，从而上调 STX6。STX6的过表达逆转了KDM4A-AS1耗竭对HCC恶性行为的抑制作用：结论：KDM4A-AS1通过miR-4306上调STX6，促进了HCC细胞的迁移、侵袭和生长。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Critical Reviews in Eukaryotic Gene Expression 生物-生物工程与应用微生物

CiteScore

2.70

自引率

0.00%

发文量

审稿时长

1 months

期刊介绍： Critical ReviewsTM in Eukaryotic Gene Expression presents timely concepts and experimental approaches that are contributing to rapid advances in our mechanistic understanding of gene regulation, organization, and structure within the contexts of biological control and the diagnosis/treatment of disease. The journal provides in-depth critical reviews, on well-defined topics of immediate interest, written by recognized specialists in the field. Extensive literature citations provide a comprehensive information resource. Reviews are developed from an historical perspective and suggest directions that can be anticipated. Strengths as well as limitations of methodologies and experimental strategies are considered.