Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Kunming Medical University, No. 1168 Chunrongxi Road, Chenggong District, Kunming, Yunnan Province, China.
Department of Hepatobiliary Surgery, The Second People's Hospital of Chengdu, Chengdu, China.
World J Surg Oncol. 2022 Mar 3;20(1):67. doi: 10.1186/s12957-022-02535-z.
Hint1 is a novel tumor suppressor gene, and inactivation of its expression is closely associated with the carcinogenesis of a variety of malignancies. The effects of Hint1 deficiency on the competing endogenous RNA (ceRNA) regulatory network in the context of HCC remains to be fully characterized. This study aims to explore Hint1-related hub lncRNAs in HCC and to establish a reliable prognostic model for HCC patients based on these hub lncRNAs.
lncRNA + mRNA microarray was used to identify differentially expressed (DE) lncRNAs and mRNAs in Huh7 cells before and after Hint1 knockdown. A Hint1-related ceRNA network was mapped by bioinformation technology. The DEmRNAs in the network were analyzed via GO and KEGG enrichment analyses. Hub DElncRNAs associated with HCC patient prognosis were then detected through univariate and multivariate Cox regression analyses and were incorporated into a prognostic model. The prognostic value of this model was then assessed through the use of Kaplan-Meier curves, time-related ROC analyses, and nomograms. We also utilized Kaplan-Meier curves to validate the relationship between hub lncRNAs and the overall survival (OS) of HCC patients. Finally, A Hint1-related core ceRNA network based on the hub DElncRNAs and DEmRNAs was mapped.
We identified 417 differentially expressed DElncRNAs and 2096 DEmRNAs in Huh7 cells before and after Hint1 knockdown. Three hub DElncRNAs (LINC00324, SNHG3, and DIO3OS) in the Hint1-associated ceRNA network were screened out using univariate and multivariate Cox regression analyses. A hepatocellular carcinoma (HCC) prognostic risk-scoring model and nomogram were constructed using these three hub lncRNAs, and it was confirmed that the risk score of the model could be used as an independent predictor of HCC prognosis. A Hint1-related core ceRNA network based on the hub DElncRNAs and DEmRNAs was also mapped.
We constructed a reliable prognostic model for HCC patients based on three Hint1-related hub lncRNAs, and we believe these three hub lncRNAs may play critical roles in hepatocarcinogenesis, and progression.
Hint1 是一种新型肿瘤抑制基因，其表达失活与多种恶性肿瘤的癌变密切相关。Hint1 缺失对肝癌中竞争内源性 RNA（ceRNA）调控网络的影响仍有待充分描述。本研究旨在探索肝癌中与 Hint1 相关的 hub lncRNA，并基于这些 hub lncRNA 为肝癌患者建立可靠的预后模型。
采用 lncRNA+mRNA 微阵列技术鉴定 Hint1 敲低前后 Huh7 细胞中差异表达的 lncRNA 和 mRNA。通过生物信息技术构建 Hint1 相关 ceRNA 网络。对网络中的差异表达 mRNA（DEmRNA）进行 GO 和 KEGG 富集分析。通过单因素和多因素 Cox 回归分析检测与 HCC 患者预后相关的 hub DElncRNA，并将其纳入预后模型。然后通过 Kaplan-Meier 曲线、时间相关 ROC 分析和列线图评估该模型的预后价值。我们还使用 Kaplan-Meier 曲线验证了 hub lncRNA 与 HCC 患者总生存期（OS）的关系。最后，基于 hub DElncRNA 和 DEmRNA 构建了 Hint1 相关的核心 ceRNA 网络。
我们鉴定了 Hint1 敲低前后 Huh7 细胞中 417 个差异表达的 DElncRNA 和 2096 个 DEmRNA。通过单因素和多因素 Cox 回归分析，从 Hint1 相关 ceRNA 网络中筛选出 3 个 hub DElncRNA（LINC00324、SNHG3 和 DIO3OS）。使用这 3 个 hub lncRNA 构建了肝癌预后风险评分模型和列线图，并证实模型的风险评分可作为 HCC 预后的独立预测因子。还基于 hub DElncRNA 和 DEmRNA 构建了 Hint1 相关的核心 ceRNA 网络。
我们基于 3 个与 Hint1 相关的 hub lncRNA 构建了肝癌患者可靠的预后模型，我们认为这 3 个 hub lncRNA 可能在肝癌发生和进展中发挥关键作用。
