mRNA, lncRNA and Circular RNA Expression Profiles in Granulosa Cells of Infertile Women with Ovarian Endometriosis.

To explore the expression profiles of mRNAs, long-noncoding RNAs (lncRNAs), circular RNAs (circRNAs) and construct the competitive endogenous RNA networks in granulosa cells (GCs) of infertile women with ovarian endometriosis. RNA sequencing was conducted for RNA expression profiling from GCs of five women with ovarian endometriosis and five with tubal factor infertility. The differential expression of mRNAs, lncRNAs and circRNAs was compared. Then, the lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA networks were constructed. Finally, the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were performed to determine the role of the differential expression of mRNA. A total of 12,498 mRNAs, 724 lncRNAs and 2269 circRNAs were identified in ovarian endometriosis and controls. 37 mRNAs, 51 lncRNAs and 101 circRNAs were detected to be differentially expressed in women with ovarian endometriosis. Ten lncRNAs and 22 differentially expressed mRNAs were selected to build the lncRNA-miRNA-mRNA network, while 12 circRNAs and four differentially expressed mRNAs were selected to build the circRNA-miRNA-mRNA network. GO analysis suggested that the differentially expressed mRNAs were mainly involved in regulation of cell differentiation, cell cycle while KEGG pathway analysis showed that pathways involved in the MAPK signaling pathway and FoxO signaling pathway were enriched with differentially upregulated mRNAs. We generated mRNAs, lncRNAs and circRNAs expression profiles and identified differentially expressed RNAs of GCs in infertile women with ovarian endometriosis. These findings provide a basis for further understanding of the underlying etiology of endometriosis-related infertility.

Guo J ，Zeng H ，Li T ，Liang X ，Peng J ... -  《-》

Construction of Competing Endogenous RNA Networks Incorporating Transcription Factors to Reveal Differences in Granulosa Cells from Patients with Endometriosis.

Wu R ，Li J ，Li J ，Zhang N ，Zhou W ，Ren L ，Chen Q ，Li Y ... -  《-》

Construction and functional enrichment analysis of the competitive endogenous RNA regulatory network for nonarteritic anterior ischemic optic neuropathy based on high-throughput sequencing.

Based on the transcriptome high-throughput sequencing of nonarteritic anterior ischemic optic neuropathy (NAION), this study constructed a competitive endogenous RNA (ceRNA) network, enriched and analyzed it, screened long noncoding (lnc)RNAs and circular (circ)RNAs that may participate in the competitive endogenous mechanism in NAION, and inferred its function. Four milliliters of peripheral blood from NAION patients and the control group was extracted from clinical samples, transcriptome high-throughput sequencing was performed, and the sequencing data were visualized. Based on the principle of the ceRNA network, the lncRNA-micro (mi)RNA-messenger (m)RNA interaction axis and circRNA-miRNA‒mRNA interaction axes were constructed. The differentially expressed genes (DEGs) in the interaction axis were enriched and analyzed by Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG), and the functions and signalling pathways of lncRNAs and circRNAs in the interaction network were speculated. Fifty-one circRNAs were differentially expressed in the sequencing data: 25 were upregulated, and 26 were downregulated. For 996 differentially expressed lncRNAs, 317 were upregulated and 679 were downregulated, and for 1161 differentially expressed mRNAs, 698 were upregulated and 463 were downregulated. Thirty-three differentially expressed miRNAs, upregulated miRNA 18 and downregulated miRNA 15 were identified. After screening, 13 coexpressed mRNAs, 15 lncRNAs, and 3 miRNAs were finally constructed in the lncRNA-miRNA-mRNA network, and the circRNA-miRNA-mRNA network was constructed by 159 mRNAs, 26 miRNAs, and 34 circRNAs. In the lncRNA network, GO enrichment analysis obtained 182 biological processes, 12 cell components and 38 molecular functions, which are related mainly to the regulation of the activity of proteins and enzymes such as cyclic nucleotide-dependent protein kinase activity and magnesium ion-dependent protein serine/threonine phosphatase activity. KEGG analysis involved mainly the forkhead box O (FoxO) signalling pathway, apelin signalling pathway, etc. In the circRNA enrichment results, 353 biological processes, 52 cell components, and 45 molecular functions were obtained, involving mainly calcium channel regulation, neutrophil activation, mRNA transport, and metabolism. KEGG mainly involved the Wnt signalling pathway, apelin signalling pathway, Hippo signalling pathway, oxytocin signalling pathway, etc. This paper provides a new idea for lncRNAs and circRNAs to mediate the occurrence and development of NAION through the ceRNA mechanism. This study lays a foundation for the in-depth study of the pathogenesis of NAION.

Zhang M ，Wang X 《-》

Identification of a Plasma Exosomal lncRNA- and circRNA-Based ceRNA Regulatory Network in Patients With Lung Adenocarcinoma.

Exosomes have been established to be enriched with various long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) that exert various biological effects. However, the lncRNA- and circRNA-mediated coexpression competing endogenous RNA (ceRNA) regulatory network in exosomes derived from the plasma of patients with lung adenocarcinoma (LUAD) remains elusive. This study enrolled nine patients with lung adenocarcinoma and three healthy individuals, and the differential expression of messenger RNAs (mRNAs), lncRNAs, and circRNAs was detected using microarray analysis, while microRNAs (miRNAs) were detected through RNA sequencing. Additionally, bioinformatics algorithms were applied to evaluate the lncRNA-miRNA-mRNAs/circRNA-miRNA-mRNA network. Differentially expressed cicRNAs were identified via quantitative reverse transcription polymerase chain reaction (RT-qPCR). A total of 1016 lncRNAs, 1396 circRNAs, 45 miRNAs, and 699 mRNAs were differentially expressed in the plasma exosomes of patients with LUAD compared with healthy controls. Among them, 881 lncRNAs were upregulated and 135 were downregulated, 916 circRNAs were upregulated while 480 were downregulated, 45 miRNAs were upregulated while none were downregulated, and 591 mRNAs were upregulated while 108 were downregulated (p ≤ 0.05, and fold change ≥ 2). Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed the biological functions of differentially expressed RNAs. Meanwhile, the RNA networks displayed the regulatory relationship between dysregulated RNAs. Finally, RT-qPCR validated that the expression of circ-0033861, circ-0043273, and circ-0011959 was upregulated in the plasma exosome of patients with LUAD compared to healthy controls (p = 0.0327, p = 0.0002, p = 0.0437, respectively). This study proposed a newly discovered ncRNA-miRNA-mRNA/circRNA-miRNA-mRNA ceRNA network and identified that the expression of circulating circ-0033861, circ-0043273, and circ-0011959 was up-regulated in the plasma exosomes of patients with LUAD, offering valuable insights for exploring the potential function of exosomal noncoding RNA and identifying potential biomarkers for LUAD.

Zhu W ，Zhang H ，Tang L ，Fang K ，Lin N ，Huang Y ，Zhang Y ，Le H ... -  《-》

Comprehensive analysis of the coding and non-coding RNA transcriptome expression profiles of hippocampus tissue in tx-J animal model of Wilson's disease.

Wilson's disease (WD) is an autosomal recessive disorder with a genetic basis. The predominant non-motor symptom of WD is cognitive dysfunction, although the specific genetic regulatory mechanism remains unclear. Tx-J mice, with an 82% sequence homology of the ATP7B gene to the human gene, are considered the most suitable model for WD. This study employs deep sequencing to investigate the differences in RNA transcript profiles, both coding and non-coding, as well as the functional characteristics of the regulatory network involved in WD cognitive impairment. The cognitive function of tx-J mice was evaluated using the Water Maze Test (WMT). Long non-coding RNA (lncRNA), circular RNA (circRNA), and messenger RNA (mRNA) profiles were analyzed in the hippocampal tissue of tx-J mice to identify differentially expressed RNAs (DE-RNAs). Subsequently, the DE-RNAs were used to construct protein-protein interaction (PPI) networks, as well as DE-circRNAs and lncRNAs-associated competing endogenous RNA (ceRNA) expression networks, and coding-noncoding co-expression (CNC) networks. To elucidate their biological functions and pathways, the PPI and ceRNA networks were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. A total of 361 differentially expressed mRNAs (DE-mRNAs), comprising 193 up-regulated and 168 down-regulated mRNAs, 2627 differentially expressed long non-coding RNAs (DE-lncRNAs), consisting of 1270 up-regulated and 1357 down-regulated lncRNAs, and 99 differentially expressed circular RNAs (DE-circRNAs), consisting of 68 up-regulated and 31 down-regulated circRNAs, were observed in the tx-J mice group when compared to the control mice group. Gene Ontology (GO) and pathway analyses revealed that DE-mRNAs were enriched in cellular processes, calcium signaling pathways, and mRNA surveillance pathways. In contrast, the DE-circRNAs-associated competing endogenous RNA (ceRNA) network was enriched for covalent chromatin modification, histone modification, and axon guidance, whereas the DE-lncRNAs-associated ceRNA network was enriched for dendritic spine, regulation of cell morphogenesis involved in differentiation, and mRNA surveillance pathway. The study presented the expression profiles of lncRNA, circRNA, and mRNA in the hippocampal tissue of tx-J mice. Furthermore, the study constructed PPI, ceRNA, and CNC expression networks. The findings are significant in comprehending the function of regulatory genes in WD associated with cognitive impairment. These results also offer valuable information for the diagnosis and treatment of WD.

Wang D ，Xie D ，Zhang J ，Cai B ，Yang B ，Zhou L ，Huang X ... -  《Scientific Reports》