Department of Hepatopancreatobiliary Surgery, The First Hospital of Jilin University, Changchun, Jilin, P.R. China.
J Cell Biochem. 2019 Dec;120(12):19775-19783. doi: 10.1002/jcb.29283. Epub 2019 Jul 16.
Small nucleolar RNA host gene 15 (SNHG15) is a long noncoding RNA (lncRNA), which promotes progression of multiple cancers. Its specific function in hepatocellular carcinoma (HCC), however, is uncertain. The aims of our study were, therefore, to explore the role of SNHG15 in HCC. SNHG15 and miR-141-3p expression were assessed via quantitative real-time PCR (qRT-PCR) in 58 paired HCC samples and adjacent matched adjacent normal tissues. CCK-8 assay, flow cytometric examination, and wound healing/invasion assays were used to respectively assess how SNHG15 influences cell proliferation, the cell cycle, and the migratory and invasive potential of HCC cells. MicroRNA (miRNAs) that targeted SNHG15 was screened by Starbase2.0 and identified by RNA immunoprecipitation and luciferase reporter assays. SNHG15 expression was markedly increased, whereas miR-141-3p expression was substantially reduced in HCC cells and tissue samples relative to normal controls. When SNHG15 was knocked down, this resulted in a significant disruption to the proliferation, as well as the invasive and migratory ability of these HCC cells. miR-141-3p was also found to be an SNHG15 target in HCC cells. Furthermore, miR-141-3p inhibitor partially reversed the observed SNHG15 depletion-mediated reduction in HCC proliferation, migration, and invasion. By repressing miR-141-3p, SNHG15 could modulate zinc finger E-box binding homeobox 2 (ZEB2) and E2F transcription factor 3 (E2F3) expression, both of which are miR-141-3p targets. These finding suggested that SNHG15 promoted HCC progression via negative regulation of miR-141-3p, thus identifying a potential novel HCC treatment pathway.
小核仁 RNA 宿主基因 15(SNHG15)是一种长链非编码 RNA(lncRNA),可促进多种癌症的进展。然而,其在肝细胞癌(HCC)中的具体功能尚不确定。因此,本研究旨在探讨 SNHG15 在 HCC 中的作用。通过实时定量 PCR(qRT-PCR)检测 58 对 HCC 样本及其配对的癌旁正常组织中 SNHG15 和 miR-141-3p 的表达。CCK-8 检测、流式细胞术检测和划痕愈合/侵袭实验分别评估 SNHG15 如何影响 HCC 细胞的增殖、细胞周期以及迁移和侵袭能力。通过 Starbase2.0 筛选靶向 SNHG15 的 microRNA(miRNAs),并通过 RNA 免疫沉淀和荧光素酶报告基因实验进行鉴定。与正常对照相比,SNHG15 在 HCC 细胞和组织样本中表达明显增加,而 miR-141-3p 表达明显降低。当 SNHG15 被敲低时,这些 HCC 细胞的增殖、侵袭和迁移能力受到显著破坏。miR-141-3p 也是 HCC 细胞中的 SNHG15 靶点。此外,miR-141-3p 抑制剂部分逆转了观察到的 SNHG15 耗竭介导的 HCC 增殖、迁移和侵袭减少。通过抑制 miR-141-3p,SNHG15 可以调节锌指 E 盒结合同源盒 2(ZEB2)和 E2F 转录因子 3(E2F3)的表达,这两者都是 miR-141-3p 的靶点。这些发现表明,SNHG15 通过负调控 miR-141-3p 促进 HCC 进展,从而确定了一种潜在的新型 HCC 治疗途径。