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. We conducted this study to illustrate the functions and mechanism of KDM4A-AS1 in regulating HCC malignant cell behavior. KD-M4A-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. 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 up-regulated STX6. STX6 overexpression reversed the inhibitory influence of KDM4A-AS1 depletion on HCC malignant behavior. KDM4A-AS1 promotes HCC cell migration, invasion, and growth by upregulating STX6 via miR-4306.

中文翻译：

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

背景：肝细胞癌（HCC）作为一种原发性肝脏恶性肿瘤，通常由慢性肝病和肝硬化诱发。生物信息学分析表明，长链非编码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。目的：阐明KDM4A-AS1在调控肝癌恶性细胞行为中的功能和机制。方法：通过逆转录定量聚合酶链反应 (RT-qPCR) 检测 KDM4A-AS1、microRNA (miR)-4306 和信使 RNA 突触蛋白 6 (STX6) 的表达。通过集落形成测定、流式细胞术、伤口愈合和 Transwell 测定来测量 HCC 细胞增殖、凋亡、迁移和侵袭。基因之间的相互作用通过 RNA 免疫沉淀和荧光素酶报告基因测定进行验证。进行蛋白质印迹以量化 STX6 或凋亡标记物的蛋白质表达。结果：KDM4A-AS1在HCC细胞和组织中高表达。KDM4A-AS1 敲低导致 HCC 细胞凋亡增强，并抑制 HCC 细胞增殖、迁移和侵袭。MiR-4306 与 STX6 结合并负向调节。KDM4A-AS1 直接结合 miR-4306，从而上调 STX6。STX6 过表达逆转了 KDM4A-AS1 缺失对 HCC 恶性行为的抑制影响。结论：KDM4A-AS1 通过 miR-4306 上调 STX6 促进 HCC 细胞迁移、侵袭和生长。