Zhou Ting, Li Mingming, Xiao Zhijun, Cai Jian, Zhao Weiwei, Duan Jingjing, Yang Zhen, Guo Zhijun, Chen Yitian, Cai Weijia, Huang Piaopiao, He Chaoyong, Xu Feng
Department of Pharmacology, China Pharmaceutical University, Nanjing, China.
Department of Pharmacy, Fengxian Hospital, Southern Medical University, Shanghai, China.
Front Oncol. 2021 Sep 28;11:744251. doi: 10.3389/fonc.2021.744251. eCollection 2021.
Circular RNAs (circRNAs) and long noncoding RNAs (lncRNAs) have been considered as biomarkers or regulators in many diseases. However, the exact role of circRNA- or lncRNA-mediated competing endogenous RNA (ceRNA) networks in the modulation of depression pathogenesis-relevant processes is not clear. In this study, we profiled whole transcriptome in depression patients' blood samples microarray analysis. As a result, a total of 340 circRNAs, 398 lncRNAs, 206 miRNAs, and 92 mRNAs were differentially expressed between the depression and control groups. Then, we constructed ceRNA networks according to the differentially expressed genes (DEGs). Using bioinformatics analysis, 89 pairs of circRNA-ceRNA and 49 pairs of lncRNA-ceRNA networks were obtained. Since depression is a broad and heterogeneous condition that is known as promoter for many chronic diseases including cancer, so we further dug out 28 circRNAs, 61 lncRNAs, 26 miRNAs, and 29 mRNAs that are associated with cancer. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that the DEGs were significantly enriched in cancer-related signaling pathways such as MAPK, Wnt, IL-17, Ras, and PI3K-Akt. Genes involved in the above pathways such as S100A9, GATA2, SRFP5, SLC45A3, NTRK1, FRZB, has_circ_0014221, has_circ_0014220, and has_circ_0087100 were dysregulated in various cancer cell lines by stress hormones induced. HDC, GATA2, SLC45A3, and NTRK1 were downregulated in tumor-bearing mice subjected to chronic unpredictable mild stress (CUMS). LncRNA-mediated ceRNA network validation showed that overexpression of miR-4530 declined HDC level. Our findings highlight the potential circRNA- and lncRNA-mediated ceRNA regulatory mechanisms in the pathogenesis of depression and as potential biomarkers in depression cancer comorbidity through the pathways of IL-17 or histidine metabolism.
环状RNA（circRNAs）和长链非编码RNA（lncRNAs）已被视为多种疾病中的生物标志物或调节因子。然而，circRNA或lncRNA介导的竞争性内源RNA（ceRNA）网络在抑郁症发病机制相关过程调节中的具体作用尚不清楚。在本研究中，我们通过微阵列分析对抑郁症患者血液样本进行了全转录组分析。结果显示，抑郁症组和对照组之间共有340种circRNAs、398种lncRNAs、206种miRNAs和92种mRNAs存在差异表达。然后，我们根据差异表达基因（DEGs）构建了ceRNA网络。通过生物信息学分析，获得了89对circRNA-ceRNA和49对lncRNA-ceRNA网络。由于抑郁症是一种广泛且异质性的疾病，被认为是包括癌症在内的许多慢性疾病的促发因素，因此我们进一步挖掘出了28种与癌症相关的circRNAs、61种lncRNAs、26种miRNAs和29种mRNAs。基因本体（GO）和京都基因与基因组百科全书（KEGG）分析表明，DEGs在与癌症相关的信号通路如MAPK、Wnt、IL-17、Ras和PI3K-Akt中显著富集。参与上述通路的基因如S100A9、GATA2、SRFP5、SLC45A3、NTRK1、FRZB、has_circ_0014221、has_circ_0014220和has_circ_0087100在各种癌细胞系中因应激激素诱导而失调。在遭受慢性不可预测轻度应激（CUMS）的荷瘤小鼠中，HDC、GATA2、SLC45A3和NTRK1表达下调。lncRNA介导的ceRNA网络验证表明，miR-4530的过表达降低了HDC水平。我们的研究结果突出了circRNA和lncRNA介导的ceRNA在抑郁症发病机制中的潜在调节机制，以及通过IL-17或组氨酸代谢途径在抑郁症与癌症共病中作为潜在生物标志物的作用。
