Ruan Lihong, Xie Yuanyuan, Liu Fangmei, Chen Xuehua
Department of Gynecology and Obstetrics, Jinan Central Hospital Affiliated to Shandong University, Jinan, 250013, China.
Department of Gynecology and Obstetrics, Jinan Central Hospital Affiliated to Shandong University, Jinan, 250013, China.
Eur J Obstet Gynecol Reprod Biol. 2018 Mar;222:31-38. doi: 10.1016/j.ejogrb.2018.01.006. Epub 2018 Jan 9.
This study aims to identify serum microRNAs (miRNAs) related to ovarian cancer.
MiRNA profiling data (GSE79943) were generated from the Gene Expression Omnibus, including 3 serum samples from healthy individuals and 4/3/16/6 serum samples from patients with ovarian cancer stage I/II/III/IV. Differentially expressed miRNAs (DEmiRNAs) were identified between controls and ovarian cancer stage I/II/III/IV by using limma package (p-value <0.05 and |log fold change| ≥0.5). miRWALK2.0 database was used to find experiment-validated targets of DEmiRNAs, and CTD database was utilized to screen known genes related to ovarian cancer. clusterProfiler package was used to perform pathway enrichment analysis of DEmiRNAs. Targets of DEmiRNAs were validated by using GSE40595, involving 8 normal ovarian stroma, 31 ovarian cancer stroma, 6 human ovarian surface epthelium, and 32 ovarian tumor epthelial component.
Between stage I/II/III/IV and control, 39/143/29/39 DEmiRNAs were identified, which were regarded as key miRNAs. Between 4 DEmiRNA sets, 15 common DEmiRNAs were identified (e.g. up-regulated hsa-miR-1181 and hsa-miR-4314). Hsa-miR-1181 participated in "Jak-STAT signaling pathway" and "miRNAs in cancer"; hsa-miR-4314 took part in cancer-related pathways. STAT3 and KRAS, known marker genes of ovarian cancer, were targeted by hsa-miR-1181 and hsa-miR-4314, respectively. Besides, FOXP1 was targeted by hsa-miR-1181; FOXP1-AS1 and FOXP1-IT1 were down-regulated in ovarian cancer. GRWD1, IP6K1, and NEGR1 were targeted by hsa-miR-4314; GRWD1, IP6K1, and NEGR1 were down-regulated in ovarian tumor.
MiR-1181 and miR-4314 might promote ovarian tumorigenesis via down-regulating FOXP1 and GRWD1/IP6K1/NEGR1, respectively. In addition, the 15 common DEmiRNAs might provide directions for ovarian cancer diagnosis.
本研究旨在鉴定与卵巢癌相关的血清微小RNA（miRNA）。
从基因表达综合数据库获取miRNA谱数据（GSE79943），包括3份健康个体的血清样本以及来自I/II/III/IV期卵巢癌患者的4/3/16/6份血清样本。使用limma软件包在对照组与I/II/III/IV期卵巢癌之间鉴定差异表达的miRNA（DEmiRNA）（p值<0.05且|log倍数变化|≥0.5）。利用miRWALK2.0数据库查找DEmiRNA经实验验证的靶标，并使用CTD数据库筛选与卵巢癌相关的已知基因。使用clusterProfiler软件包对DEmiRNA进行通路富集分析。通过GSE40595验证DEmiRNA的靶标，该数据集包含8份正常卵巢基质、31份卵巢癌基质、6份人卵巢表面上皮以及32份卵巢肿瘤上皮成分。
在I/II/III/IV期与对照组之间，分别鉴定出39/143/29/39个DEmiRNA，这些被视为关键miRNA。在4组DEmiRNA中，鉴定出15个共同的DEmiRNA（例如上调的hsa-miR-1181和hsa-miR-4314）。hsa-miR-1181参与“Jak-STAT信号通路”和“癌症中的miRNA”；hsa-miR-4314参与癌症相关通路。卵巢癌的已知标志物基因STAT3和KRAS分别是hsa-miR-1181和hsa-miR-4314的靶标。此外，FOXP1是hsa-miR-1181的靶标；FOXP1-AS1和FOXP1-IT1在卵巢癌中下调。GRWD1、IP6K1和NEGR1是hsa-miR-4314的靶标；GRWD1、IP6K1和NEGR1在卵巢肿瘤中下调。
MiR-1181和miR-4314可能分别通过下调FOXP1和GRWD1/IP6K1/NEGR1促进卵巢肿瘤发生。此外，这15个共同的DEmiRNA可能为卵巢癌诊断提供方向。
