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Abstract：
OBJECTIVE: Long noncoding RNAs (lncRNAs) exert a significant influence on various cancer-related processes through their intricate interactions with RNAs. Among these, lncRNA ZFAS1 has been implicated in oncogenic roles in multiple cancer types. Nevertheless, the intricate biological significance and underlying mechanism of ZFAS1 in the initiation and progression of hepatocellular carcinoma (HCC) remain largely unexplored.
METHODS: Analysis of The Cancer Genome Atlas Program (TCGA) database revealed a notable upregulation of lncRNA ZFAS1 in HCC tissues. To explore its function, we investigated colony formation and performed CCK-8 assays to gauge cellular proliferation and wound healing, Transwell assays to assess cellular migration, and an in vivo study employing a nude mouse model to scrutinize tumor growth and metastasis. Luciferase reporter assay was used to confirm the implicated interactions. Rescue experiments were conducted to unravel the plausible mechanism underlying the activation of the PI3K/AKT pathway by lncRNAs ZFAS1 and ATIC.
RESULTS: ZFAS1 and ATIC were significantly upregulated in the HCC tissues and cells. ZFAS1 knockdown inhibited cell proliferation and migration. We observed a direct interaction between the lncRNA ZFAS1 and ATIC. ATIC knockdown also suppressed cell proliferation and migration. SC79, an activator of AKT, partially restores the effects of lncRNA ZFAS1/ATIC knockdown on cell proliferation and migration. Knockdown of lncRNA ZFAS1/ATIC inhibited tumor growth and lung metastasis in vivo.
CONCLUSIONS: Overall, lncRNA ZFAS1 regulates ATIC transcription and contributes to the growth and migration of HCC cells through the PI3K/AKT signaling pathway.
METHODS: Analysis of The Cancer Genome Atlas Program (TCGA) database revealed a notable upregulation of lncRNA ZFAS1 in HCC tissues. To explore its function, we investigated colony formation and performed CCK-8 assays to gauge cellular proliferation and wound healing, Transwell assays to assess cellular migration, and an in vivo study employing a nude mouse model to scrutinize tumor growth and metastasis. Luciferase reporter assay was used to confirm the implicated interactions. Rescue experiments were conducted to unravel the plausible mechanism underlying the activation of the PI3K/AKT pathway by lncRNAs ZFAS1 and ATIC.
RESULTS: ZFAS1 and ATIC were significantly upregulated in the HCC tissues and cells. ZFAS1 knockdown inhibited cell proliferation and migration. We observed a direct interaction between the lncRNA ZFAS1 and ATIC. ATIC knockdown also suppressed cell proliferation and migration. SC79, an activator of AKT, partially restores the effects of lncRNA ZFAS1/ATIC knockdown on cell proliferation and migration. Knockdown of lncRNA ZFAS1/ATIC inhibited tumor growth and lung metastasis in vivo.
CONCLUSIONS: Overall, lncRNA ZFAS1 regulates ATIC transcription and contributes to the growth and migration of HCC cells through the PI3K/AKT signaling pathway.
摘要：
目的：长链非编码RNA（lncRNA）通过其与RNA的复杂相互作用对各种癌症相关过程产生重大影响。其中,lncRNAZFAS1与多种癌症类型的致癌作用有关。然而，ZFAS1在肝细胞癌(HCC)的发生和进展中的复杂生物学意义和潜在机制仍未被研究.
方法：癌症基因组图谱计划（TCGA）数据库的分析显示，在HCC组织中lncRNAZFAS1显著上调。为了探索它的功能，我们研究了集落形成并进行了CCK-8测定以测量细胞增殖和伤口愈合，用于评估细胞迁移的Transwell测定法，和使用裸鼠模型检查肿瘤生长和转移的体内研究。使用荧光素酶报告基因测定来确认所涉及的相互作用。进行了挽救实验，以阐明lncRNAsZFAS1和ATIC激活PI3K/AKT途径的潜在机制。
结果：ZFAS1和ATIC在HCC组织和细胞中显著上调。ZFAS1敲低抑制细胞增殖和迁移。我们观察到lncRNAZFAS1和ATIC之间的直接相互作用。ATIC敲低也抑制细胞增殖和迁移。SC79，AKT的激活剂，部分恢复lncRNAZFAS1/ATIC敲低对细胞增殖和迁移的影响。敲除lncRNAZFAS1/ATIC在体内抑制肿瘤生长和肺转移。
结论：总体而言，lncRNAZFAS1通过PI3K/AKT信号通路调节ATIC转录并促进HCC细胞的生长和迁移。
方法：癌症基因组图谱计划（TCGA）数据库的分析显示，在HCC组织中lncRNAZFAS1显著上调。为了探索它的功能，我们研究了集落形成并进行了CCK-8测定以测量细胞增殖和伤口愈合，用于评估细胞迁移的Transwell测定法，和使用裸鼠模型检查肿瘤生长和转移的体内研究。使用荧光素酶报告基因测定来确认所涉及的相互作用。进行了挽救实验，以阐明lncRNAsZFAS1和ATIC激活PI3K/AKT途径的潜在机制。
结果：ZFAS1和ATIC在HCC组织和细胞中显著上调。ZFAS1敲低抑制细胞增殖和迁移。我们观察到lncRNAZFAS1和ATIC之间的直接相互作用。ATIC敲低也抑制细胞增殖和迁移。SC79，AKT的激活剂，部分恢复lncRNAZFAS1/ATIC敲低对细胞增殖和迁移的影响。敲除lncRNAZFAS1/ATIC在体内抑制肿瘤生长和肺转移。
结论：总体而言，lncRNAZFAS1通过PI3K/AKT信号通路调节ATIC转录并促进HCC细胞的生长和迁移。
