基于生物信息学、荟萃分析和实验验证的肝细胞癌中miR-101-3p靶点鉴定及功能特征研究
Identification of miR-101-3p targets and functional features based on bioinformatics, meta-analysis and experimental verification in hepatocellular carcinoma.
作者信息
Li Chun-Yao, Pang Yu-Yan, Yang Hong, Li Jia, Lu Hai-Xia, Wang Han-Lin, Mo Wei-Jia, Huang Lan-Shan, Feng Zhen-Bo, Chen Gang
机构信息
Department of Pathology, The First Affiliated Hospital of Guangxi Medical University6 Shuangyong Road, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
Department of Medical Ultrasonics, The First Affiliated Hospital of Guangxi Medical University6 Shuangyong Road, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
出版信息
Am J Transl Res. 2017 May 15;9(5):2088-2105. eCollection 2017.
BACKGROUND
MiR-101-3p has been reported to suppress invasion and metastasis in hepatocellular carcinoma (HCC) cells. However, the relevant mechanisms are still unclear. The research seeks to determine systematic value of miR-101-3p in HCC, and comprehensively summarize the predicted target genes as well as their potential function, pathways and networks in HCC.
METHODS
The miR-101-1 profiles in 353 HCC patients from The Cancer Genome Atlas (TCGA) were analyzed. Meta-analysis was performed to estimate relationship of miR-101 (including precursor and mature miR-101) with clinical features and prognosis in HCC. Further, the promising targets of miR-101-3p were predicted and followed with Gene Ontology (GO), pathway and network analysis. In addition, the functional impact of miR-101-3p was confirmed with experiments in HCC cells.
RESULTS
In TCGA data, low-expression of miR-101-1 might be a diagnostic (AUC: 0.924, 95% CI: 0.894-0.953) and prognostic (HR=1.55) marker for HCC. Down-regulated miR-101-1 also correlated with poor differentiation, advanced TNM stage, lymph node metastasis and high AFP level of HCC. Meta-analysis revealed that miR-101 down-regulation were associated with poor prognosis, high AFP level and advanced TNM stage of HCC. Moreover, 343 hub genes were filtered and miR-101-3p may be involved in intracellular signaling cascade, transcription, metabolism and cell proliferation. Focal adhesion and pathways in cancer were also significantly enriched. experiments demonstrated that miR-101-3p inhibited proliferation and promoted apoptosis in HCC cells.
CONCLUSIONS
MiR-101-1 may be a prospective biomarker for diagnosis and prognosis of HCC. Potential targets of miR-101-3p could regulate genesis and development of HCC. The data offers insights into biological significances and promising targets of miR-101-3p for further investigation and potential therapies in HCC.
背景
据报道，miR-101-3p可抑制肝癌（HCC）细胞的侵袭和转移。然而，相关机制仍不清楚。本研究旨在确定miR-101-3p在肝癌中的系统价值，并全面总结其预测的靶基因及其在肝癌中的潜在功能、途径和网络。
方法
分析了来自癌症基因组图谱（TCGA）的353例肝癌患者的miR-101-1图谱。进行荟萃分析以评估miR-101（包括前体和成熟miR-101）与肝癌临床特征和预后的关系。此外，预测了miR-101-3p的潜在靶标，并进行了基因本体论（GO）、途径和网络分析。另外，通过肝癌细胞实验证实了miR-101-3p的功能影响。
结果
在TCGA数据中，miR-101-1低表达可能是肝癌的诊断（AUC：0.924，95%CI：0.894-0.953）和预后（HR=1.55）标志物。miR-101-1下调还与肝癌的低分化、晚期TNM分期、淋巴结转移和高AFP水平相关。荟萃分析显示，miR-101下调与肝癌的不良预后、高AFP水平和晚期TNM分期相关。此外，筛选出343个枢纽基因，miR-101-3p可能参与细胞内信号级联、转录、代谢和细胞增殖。粘着斑和癌症途径也显著富集。实验表明，miR-101-3p抑制肝癌细胞增殖并促进其凋亡。
结论
miR-101-1可能是肝癌诊断和预后的潜在生物标志物。miR-101-3p的潜在靶标可调节肝癌的发生和发展。这些数据为miR-101-3p在肝癌进一步研究和潜在治疗中的生物学意义及有前景的靶标提供了见解。
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