Department of Hepatobiliary and Pancreatic Surgery, Third Affiliated Hospital of Soochow University, 185th Juqian Street, Changzhou, Jiangsu, 213003, China.
Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, Jiangsu, 225300, China.
J Cancer Res Clin Oncol. 2024 Jul 13;150(7):351. doi: 10.1007/s00432-024-05877-1.
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.
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.
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.
Overall, lncRNA ZFAS1 regulates ATIC transcription and contributes to the growth and migration of HCC cells through the PI3K/AKT signaling pathway.
长链非编码 RNA（lncRNA）通过与 RNA 的复杂相互作用，对各种癌症相关过程产生重大影响。在这些过程中，lncRNA ZFAS1 已被证明在多种癌症类型中具有致癌作用。然而，lncRNA ZFAS1 在肝细胞癌（HCC）发生和发展中的复杂生物学意义和潜在机制在很大程度上仍未得到探索。
对癌症基因组图谱计划（TCGA）数据库的分析显示，lncRNA ZFAS1 在 HCC 组织中显著上调。为了研究其功能，我们进行了集落形成和 CCK-8 测定以评估细胞增殖和伤口愈合，Transwell 测定以评估细胞迁移，以及使用裸鼠模型进行体内研究以检查肿瘤生长和转移。使用荧光素酶报告测定法证实了所涉及的相互作用。进行了挽救实验以揭示 lncRNA ZFAS1 和 ATIC 激活 PI3K/AKT 通路的潜在机制。
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 lncRNA ZFAS1 和 ATIC 之间存在直接相互作用。ATIC 敲低也抑制了细胞增殖和迁移。PI3K/AKT 信号通路的激活剂 SC79 部分恢复了 lncRNA ZFAS1/ATIC 敲低对细胞增殖和迁移的影响。ZFAS1/ATIC 敲低抑制体内肿瘤生长和肺转移。
总的来说，lncRNA ZFAS1 通过 PI3K/AKT 信号通路调节 ATIC 转录，促进 HCC 细胞的生长和迁移。
