Department of Gastroenterology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, P.R. China.
Cancer Gene Ther. 2022 Oct;29(10):1373-1383. doi: 10.1038/s41417-022-00456-3. Epub 2022 Mar 25.
The role of long noncoding RNA (lncRNAs) had been demonstrated in different types of cancer, including hepatocellular carcinoma. This study was intended to investigate the role of lncRNA small nucleolar RNA host gene 5 (SNHG5) in HCC proliferation and the liver CSC-like properties. Through functional experiments, we determined that knockdown of SNHG5 repressed HCC cell proliferation and CSC-like properties, while over-expression of SNHG5 promoted cell growth. At the same time, CSC markers (CD44, CD133, and ALDH1) and related transcription factors (OCT4, SOX2, and NANOG) were downregulated when SNHG5 was knocked down. Mechanically, RNA immunoprecipitation (RIP) and RNA pulldown assay showed that SNHG5 regulated the proliferation and CSC-like properties of HCC by binding UPF1. Further investigations showed that expression of critical components of Wnt/β-catenin pathway (β-catenin, TCF4, c-myc, cyclinD1, and c-Jun) were upregulated with depletion of UPF1 in liver CSCs, which were downregulated with depletion of SNHG5. After use of the inhibitor of Wnt/β-catenin pathway, the formation of liver CSCs sphere decreased. Taken together, SNHG5 plays a critical role to promote HCC cell proliferation and cancer stem cell-like properties via UPF1 and Wnt/β-catenin pathway.
长链非编码 RNA（lncRNA）在多种类型的癌症中发挥作用，包括肝细胞癌。本研究旨在探讨 lncRNA 小核仁 RNA 宿主基因 5（SNHG5）在 HCC 增殖和肝 CSC 样特性中的作用。通过功能实验，我们确定敲低 SNHG5 抑制 HCC 细胞增殖和 CSC 样特性，而过表达 SNHG5 促进细胞生长。同时，当 SNHG5 被敲低时，CSC 标志物（CD44、CD133 和 ALDH1）和相关转录因子（OCT4、SOX2 和 NANOG）下调。在机制上，RNA 免疫沉淀（RIP）和 RNA 下拉实验表明，SNHG5 通过结合 UPF1 来调节 HCC 的增殖和 CSC 样特性。进一步的研究表明，在肝 CSCs 中，Wnt/β-catenin 通路的关键成分（β-catenin、TCF4、c-myc、cyclinD1 和 c-Jun）的表达上调，而在 SNHG5 耗尽时下调。使用 Wnt/β-catenin 通路抑制剂后，肝 CSCs 球体的形成减少。总之，SNHG5 通过 UPF1 和 Wnt/β-catenin 通路在促进 HCC 细胞增殖和癌症干细胞样特性方面发挥关键作用。
