A comprehensive insight into the clinicopathologic significance of miR-144-3p in hepatocellular carcinoma.
A comprehensive insight into the clinicopathologic significance of miR-144-3p in hepatocellular carcinoma.
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全面了解 miR-144-3p 在肝细胞癌中的临床病理意义
DOI：
10.2147/ott.s138143
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发表时间：
2017
影响因子：
4
通讯作者：
Luo DZ
中科院分区：
文献类型：
--
作者：
Liang HW;Ye ZH;Yin SY;Mo WJ;Wang HL;Zhao JC;Liang GM;Feng ZB;Chen G;Luo DZ
关于miR-144-3p在肝细胞癌（HCC）中的特征的研究是有限的。本研究旨在探讨miR-144-3p在HCC中的表达、临床意义及潜在靶点。方法应用肿瘤基因组图谱（Cancer Genome Atlas， TCGA）和95例HCC患者的队列研究miR-144-3p在HCC中的异常表达。基于TCGA、定量逆转录聚合酶链反应（qRT-PCR）和基因表达综合（GEO），进行meta分析以积累miR-144-3p在HCC中的表达数据。此外，通过生物信息学探讨了miR-144-3p在HCC中的潜在调控机制。结果在TCGA数据（8.9139±1.5986 vs 10.7721±0.9156，P<0.001）和qRT-PCR验证（1.3208±0.7594 vs 2.6200±0.9263，P<0.001）中，MiR-144-3p在HCC中表达明显下调。基于TCGA、qRT-PCR和GEO数据的meta分析证实了一致的结果（标准均差= - 0.854,95% CI: - 1.224 ~ - 0.484， P<0.001）。miR-144-3p的受试者工作特征曲线在TCGA数据中（曲线下面积[AUC] =0.852, 95% CI: 0.810 ~ 0.894， P<0.001）和qrp - pcr验证中（AUC =0.867, 95% CI: 0.817 ~ 0.916， P<0.001），特别是在甲胎儿蛋白阴性的HCC患者中（AUC =0.900, 95% CI: 0.839 ~ 0.960， P<0.001）均具有显著的诊断价值。此外，我们通过生物信息学确定了HCC中miR-144-3p的119个潜在靶点。基因本体论和京都基因与基因组百科通路分析显示，几种重要的生物学功能和通路与HCC的发病相关，其中包括p53信号通路。结论MiR-144-3p可能是一种抑癌microRNA，通过调控多种信号通路对HCC的进展起重要作用。因此，与miR-144-3p的相互作用可能在未来为HCC提供一种新的治疗策略。
Background Studies which focused on the character of miR-144-3p in hepatocellular carcinoma (HCC) are limited. This study aimed to explore the expression, clinical significance and the potential targets of miR-144-3p in HCC. Methods The Cancer Genome Atlas (TCGA) and a cohort of 95 cases of HCC were applied to investigate aberrant miR-144-3p expression in HCC. A meta-analysis was performed to accumulate data on miR-144-3p expression in HCC based on TCGA, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Gene Expression Omnibus (GEO). Additionally, the potential regulatory mechanisms of miR-144-3p in HCC were explored by bioinformatics. Results MiR-144-3p expression was downregulated distinctly in HCC compared to para-HCC tissue both in TCGA data (8.9139±1.5986 vs 10.7721±0.9156, P<0.001) and in our qRT-PCR validation (1.3208±0.7594 vs 2.6200±0.9263, P<0.001). The meta-analysis based on TCGA, qRT-PCR and GEO data confirmed a consistent result (standard mean difference =−0.854, 95% CI: −1.224 to −0.484, P<0.001). The receiver operating characteristic curve of miR-144-3p gained a significant diagnostic value both in TCGA data (area under the curve [AUC] =0.852, 95% CI: 0.810 to 0.894, P<0.001) and in qRT-PCR validation (AUC =0.867, 95% CI: 0.817 to 0.916, P<0.001), especially in alpha-fetoprotein–negative HCC patients (AUC =0.900, 95% CI: 0.839 to 0.960, P<0.001). Furthermore, we identified 119 potential targets of miR-144-3p in HCC by bioinformatics. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that several significant biologic functions and pathways correlated with the pathogenesis of HCC, including the p53 signaling pathway. Conclusion MiR-144-3p may function as a cancer suppressor microRNA, which is essential for HCC progression through the regulation of various signaling pathways. Thus, interactions with miR-144-3p may provide a novel treatment strategy for HCC in the future.