Long noncoding RNAs (lncRNAs) are emerging as crucial contributors to the development of hepatocellular carcinoma (HCC) and are involved in the stemness regulation of liver cancer stem cells (LCSCs). However, cancer cell stemness-associated lncRNAs and their relevance in prediction of clinical prognosis remain largely unexplored. In this study, through the transcriptome-wide screen, we identified a total of 136 LCSC-associated lncRNAs. We evaluated the prognostic value of these lncRNAs and optimally established an 11-lncRNA (including AC008622.2, AC015908.3, AC020915.2, AC025176.1, AC026356.2, AC099850.3, CYTOR, DDX11-AS1, HTR2A-AS1, LINC02870, and SNHG3) prognostic risk model. Multivariate analysis revealed that the risk score is an independent prognostic predictor for HCC patients, which outperforms the traditional clinical pathological factors. Gene set enrichment analysis suggested that the high-risk score reflects the alteration of pathways involved in cell cycle, oxidative phosphorylation, and metabolism. Furthermore, functional studies on SNHG12, the leading candidate of the risk lncRNAs, revealed that knockdown of SNHG12 reduces the abilities of HCC cells stemness, proliferation, migration, and invasion. In summary, we constructed a prognostic risk model based on 11 LCSC-associated lncRNAs, which might be a promising prognostic predictor for HCC patients and highlight the involvement of lncRNAs in LCSC-associated treatment strategy in clinical practice.

中文翻译：

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鉴定癌细胞干性相关长链非编码 RNA 以预测肝细胞癌患者的预后

长链非编码 RNA (lncRNA) 正在成为肝细胞癌 (HCC) 发展的关键因素，并参与肝癌干细胞 (LCSC) 的干细胞调控。然而，癌细胞干性相关的 lncRNA 及其在预测临床预后中的相关性在很大程度上仍未得到探索。在这项研究中，通过全转录组筛选，我们共鉴定了 136 个 LCSC 相关的 lncRNA。我们评估了这些lncRNAs的预后价值和最佳建立一个11 lncRNA（包括AC008622.2，AC015908.3，AC020915.2，AC025176.1，AC026356.2，AC099850.3，CYTOR，DDX11-AS1，HTR2A-AS1、LINC02870和SNHG3 ) 预后风险模型。多变量分析显示，风险评分是 HCC 患者的独立预后预测因子，优于传统的临床病理因素。基因集富集分析表明，高风险评分反映了参与细胞周期、氧化磷酸化和代谢途径的改变。此外，对风险 lncRNA 的主要候选者SNHG12 的功能研究表明，SNHG12 的敲低降低 HCC 细胞的干细胞、增殖、迁移和侵袭能力。总之，我们基于 11 种 LCSC 相关的 lncRNA 构建了一个预后风险模型，这可能是 HCC 患者的一个有希望的预后预测因子，并突出了 lncRNA 在临床实践中参与 LCSC 相关治疗策略的作用。