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基于 1167 例头颈部鳞状细胞癌中 miRNA 芯片和 miRNA 测序数据的 miRNA-99a-3p 的表达水平及其潜在机制研究。

Expression level and prospective mechanism of miRNA-99a-3p in head and neck squamous cell carcinoma based on miRNA-chip and miRNA-sequencing data in 1, 167 cases.

机构信息

Department of Otolaryngology Head and Neck Surgery, 303 Hospital of PLA Guangxi Zhuang Autonomous Region, Nanning, China.

Department of Cell Biology and Genetics, School of Pre-clinical Medicine, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China.

出版信息

Pathol Res Pract. 2019 May;215(5):963-976. doi: 10.1016/j.prp.2019.02.002. Epub 2019 Feb 4.

Abstract

BACKGROUND

The role of miR-99a-3p in Head and neck squamous cell carcinoma (HNSCC) has not been reported. Therefore, in this study, we examined the expression level and its molecular mechanisms of miR-99a-3p in HNSCC.

MATERIALS AND METHODS

MiR-99a-3p-related miRNA-chip and miRNA-sequencing data were collected. We then carried out meta-analyses to pool the standard mean difference (SMD) value and generate a summarized receiver operating characteristic (sROC) curve. MiR-99a-3p mimic was transfected into FaDu cells and those genes influenced by miR-99a-3p were gathered. The target genes were also predicted from 12 tools through miRwalk2.0, and combined with differentially expressed genes in HNSCC from the The Cancer Genome Atlas and Genotype-Tissue Expression sequencing databases. FunRich and DAVID were used for the pathway signaling analyses for the potential targets of miR-99a-3p in HNSCC.

RESULTS

The SMD was -0.30 (95% CI: -0.51, -0.08) in the fixed-effect model and -0.28 (95% CI: -0.67, 0.10) in the random-effect model (I2 = 60%), indicating a reduced expression level of miR-99a-3p in HNSCC tissues based on 1167 cases. In the sROC curve, the area under the curve (AUC) was 0.77 (95% CI: 0.73, 0.81). The 251 potential targets of miR-99a-3p were enriched in several pathways related to cancer, with the "Pathways in cancer" standing at the top. vascular endothelial growth factor A was selected as an example with up-regulated trend in HNSCC tissues.

CONCLUSION

MiR-99a-3p exhibits a significant lower expression status in HNSCC, and this reduced or deletion status promotes the malignant progression of HNSCC. However, its molecular mechanism is still unclear and requires further investigation.

摘要

背景

miR-99a-3p 在头颈部鳞状细胞癌(HNSCC)中的作用尚未报道。因此,在本研究中,我们检查了 miR-99a-3p 在 HNSCC 中的表达水平及其分子机制。

材料和方法

收集了 miR-99a-3p 相关的 miRNA 芯片和 miRNA 测序数据。然后,我们进行了荟萃分析,以汇总标准均数差(SMD)值并生成汇总受试者工作特征(sROC)曲线。将 miR-99a-3p 模拟物转染到 FaDu 细胞中,并收集受 miR-99a-3p 影响的基因。通过 miRwalk2.0 从 12 个工具预测靶基因,并与 The Cancer Genome Atlas 和 Genotype-Tissue Expression 测序数据库中 HNSCC 的差异表达基因相结合。使用 FunRich 和 DAVID 对 miR-99a-3p 在 HNSCC 中的潜在靶基因进行通路信号分析。

结果

在固定效应模型中,SMD 为-0.30(95%CI:-0.51,-0.08),在随机效应模型中为-0.28(95%CI:-0.67,0.10)(I2=60%),表明基于 1167 例,HNSCC 组织中 miR-99a-3p 的表达水平降低。在 sROC 曲线中,曲线下面积(AUC)为 0.77(95%CI:0.73,0.81)。miR-99a-3p 的 251 个潜在靶基因富集在与癌症相关的几个通路中,其中“癌症通路”位居榜首。血管内皮生长因子 A 是 HNSCC 组织中上调趋势的一个例子。

结论

miR-99a-3p 在 HNSCC 中表达水平显著降低,这种降低或缺失状态促进了 HNSCC 的恶性进展。然而,其分子机制尚不清楚,需要进一步研究。

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