Feng Penghui, Ge Zhitong, Guo Zaixin, Lin Lin, Yu Qi
Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Front Mol Biosci. 2021 Jun 11;8:687576. doi: 10.3389/fmolb.2021.687576. eCollection 2021.
Previous studies demonstrated that could repress various cancers on proliferation, angiogenesis, and metastasis. However, little attention has been paid to its role in ovarian cancer as a novel biomarker or intervention target, especially its clinical significance and underlying regulatory network. A meta-analysis of six microarrays was adopted here to determine the expression trend of , and was further validated by gene expression profile data and cellular experiments. We explored the functional annotations through enrichment analysis for the differentially expressed genes targeted by . Subsequently, we identified two hub genes, and , based on interaction analysis using two online archive tools, miRWALK (it consolidates the resources of 12 miRNA-focused servers) and Gene Expression Profiling Interactive Analysis (GEPIA). Finally, we validated their characteristics and clinical significance in ovarian cancer. The comprehensive meta-analysis revealed that was markedly downregulated in clinical and cellular specimens. Transfection of the mimic could significantly inhibit cellular proliferation. Concerning its target genes, they were involved in diverse biological processes related to tumorigenesis, such as cell proliferation, migration, and the apoptosis signaling pathway. Moreover, interaction analysis proved that two hub genes, and , were highly associated with poor prognosis in ovarian cancer. These integrated bioinformatic analyses indicated that was dramatically downregulated in ovarian cancer as a tumor suppressor. The upregulation of its downstream modulators, and , was associated with an unfavorable prognosis. Thus, the present study has identified as a potential intervention target for ovarian cancer based on our bioinformatic analysis processes.
先前的研究表明，[具体物质]可在增殖、血管生成和转移方面抑制多种癌症。然而，作为一种新型生物标志物或干预靶点，其在卵巢癌中的作用，尤其是其临床意义和潜在调控网络，却很少受到关注。本研究采用对六个微阵列的荟萃分析来确定[具体物质]的表达趋势，并通过基因表达谱数据和细胞实验进一步验证。我们通过对[具体物质]靶向的差异表达基因进行富集分析来探索功能注释。随后，我们基于使用两个在线存档工具miRWALK（整合了12个专注于miRNA的服务器的资源）和基因表达谱交互分析（GEPIA）的相互作用分析，鉴定出两个枢纽基因[基因名称1]和[基因名称2]。最后，我们在卵巢癌中验证了它们的特征和临床意义。综合荟萃分析显示，[具体物质]在临床和细胞样本中明显下调。转染[具体物质]模拟物可显著抑制细胞增殖。关于其靶基因，它们参与了与肿瘤发生相关的多种生物学过程，如细胞增殖、迁移和凋亡信号通路。此外，相互作用分析证明，两个枢纽基因[基因名称1]和[基因名称2]与卵巢癌的不良预后高度相关。这些综合生物信息学分析表明，[具体物质]作为一种肿瘤抑制因子在卵巢癌中显著下调。其下游调节因子[基因名称1]和[基因名称2]的上调与不良预后相关。因此，本研究基于我们的生物信息学分析过程，已将[具体物质]确定为卵巢癌的潜在干预靶点。
