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Female common carp grow faster than male individuals, implying that rearing females could be more profitable in aquaculture. Non-coding RNAs (ncRNAs) serve as versatile regulators with multiple functions in diverse biological processes. However, the roles of ncRNAs in the sex differentiation of common carp are less studied. In this study, we investigated the expression profiles of ncRNAs, including miRNAs, lncRNAs, and circRNAs, in the gonads to comprehend the roles of ncRNAs in sex differentiation in common carp. A substantial number of differentially expressed (DE) ncRNAs in ovaries and testes were identified. Some miRNAs, notably miR-205, miR-214, and miR-460-5p, might modulate hormone synthesis and thus maintain sex. A novel miRNA, novel_158, was predicted to suppress the expression of foxl3. DE lncRNAs were associated with oocyte meiosis, GnRH signaling pathways, and steroid biosynthesis, while DE circRNA target genes were enriched in the WNT signaling pathway and MAPK signaling pathway. We also analyzed ncRNA-mRNA interactions to shed light on the crosstalk between competing endogenous RNAs (ceRNAs), which is the critical mechanism by which lncRNAs and circRNAs function. Some lncRNAs and circRNAs may be able to competitively bind novel_313, a new miRNA, and thus regulate hsd17β3. Our research will provide a valuable resource for understanding the genetic basis of gonadal differentiation and development in common carp. [ABSTRACT FROM AUTHOR]

The eye is a superficial organ directly exposed to the surrounding environment. Thus, the toxicity of nanoparticle (NP) pollutants to the eye may be potentially severer relative to inner organs and needs to be monitored. However, the cytotoxic mechanisms of NPs on the eyes remain rarely reported. This study was to screen crucial genes associated with NPs-induced retinal injuries. The gene expression profiles in the retina induced by NPs [GSE49371: Au20, Au100, Si20, Si100; GSE49048: presumptive therapeutic concentration (PTC) TiO 2 , 10PTC TiO 2 ] and commonly used retinal cell injury models (optic nerve injury procedure: GSE55228, GSE120257 and GSE131486; hypoxia exposure: GSE173233, GSE151610, GSE135844; H 2 O 2 exposure: GSE122270) were obtained from the Gene Expression Omnibus database. A total of 381 differentially expressed genes (including 372 mRNAs and 9 lncRNAs) were shared between NP exposure and the optic nerve injury model when they were compared with their corresponding controls. Function enrichment analysis of these overlapped genes showed that Tlr2 , Crhbp , Ccl2 , Cxcl10 , Fas , Irf8 , Socs3 , Stat3 , Gbp6 , Casp1 and Syk were involved in inflammatory- and apoptotic-related processes. Protein-protein interaction network analysis revealed eight of them ( Tlr2 , Ccl2 , Cxcl10 , Irf8 , Socs3 , Stat3 , Casp1 and Syk ) were hub genes. Moreover, Socs3 could interact with upstream Stat3 and downstream Fas / Casp1 / Ccl2 / Cxcl10 ; Irf8 could interact with upstream Tlr2 , Syk and downstream Cxcl10 . Competing endogenous RNAs network analysis identified Socs3 , Irf8 , Gdf6 and Crhbp could be regulated by lncRNAs and miRNAs (9330175E14Rik-mmu-miR-762- Socs3 , 6430562O15Rik-mmu-miR-207- Irf8 , Gm9866-mmu-miR-669b-5p- Gdf6 , 4933406C10Rik-mmu-miR-9-5p- Crhbp ). CMap-CTD database analyses indicated the expression levels of Tlr2 , Ccl2 , Cxcl10 , Fas , Irf8 , Socs3 , Stat3 , Gbp6 , Casp1 and Syk could be reversed by folic acid. Crhbp and Gdf6 were also verified to be downregulated, while Tlr2 , Ccl2 , Irf8 , Socs3 and Stat3 were upregulated in hypoxia/H 2 O 2 -induced retinal injury models. Hereby, our findings suggest that Crhbp , Irf8 , Socs3 and Gdf6 as well as their upstream mRNAs, lncRNAs and miRNAs may be potential monitoring biomarkers and therapeutic targets for NP-induced retinal injuries. Folic acid supplementation may be a preventive and therapeutic approach.

Simple Summary: The follicle development (FD) of a goat is precisely regulated by various noncoding RNAs (ncRNAs), especially by the regulatory mechanism of competing endogenous RNAs (ceRNAs). This study aimed to determine the expression patterns of messenger RNA (mRNA), long noncoding RNA, microRNA, and circular RNA during the FD of Dazhu black goats by whole-transcriptomic sequencing and analyze the regulatory mechanism of the ncRNA and ceRNA regulatory network. The results may lay a foundation for further research on FD and improving the reproductive performance of goats. The follicle development (FD) is an important factor determining litter size in animals. Recent studies have found that noncoding RNAs (ncRNAs) play an important role in FD. In particular, the role of the regulatory mechanism of competing endogenous RNAs (ceRNAs) that drive FD has attracted increasing attention. Therefore, this study explored the genetic basis of goat FD by obtaining the complete follicular transcriptome of Dazu black goats at different developmental stages. Results revealed that 128 messenger RNAs (mRNAs), 4 long noncoding RNAs (lncRNAs), 49 microRNAs (miRNAs), and 290 circular RNAs (circRNAs) were significantly differentially expressed (DE) between large and small follicles. Moreover, DEmRNAs were enriched in many signaling pathways related to FD, as well as GO terms related to molecular binding and enzyme activity. Based on the analysis of the ceRNA network (CRN), 34 nodes (1 DElncRNAs, 10 DEcircRNAs, 14 DEmiRNAs, and 9 DEmRNAs) and 35 interactions (17 DEcircRNAs–DEmRNAs, 2 DElncRNAs–DEmiRNAs, and 16 DEmRNA–DEmiRNAs) implied that the CRN could be involved in the FD of goats. In conclusion, we described gene regulation by DERNAs and lncRNA/circRNA–miRNA–mRNA CRNs in the FD of goats. This study provided insights into the genetic basis of FD in precise transcriptional regulation. [ABSTRACT FROM AUTHOR]

Simple Summary: Here, we present a novel strategy to identify key signatures of clinically-relevant co-expressed circRNA-mRNA networks in pertinent cancer-pathways that modulate the prognosis of HCC patients, by integrating clinicopathological features, circRNA and mRNA expression profiles. Five master circRNAs were identified and experimentally demonstrated to upregulate proliferate and promote transformation. Through further integration with miRNA-expression profiles, clinically-relevant competing-endogenous-RNA (ceRNA) networks of circRNA-miRNA-mRNAs were constructed. The most up-regulated nodal-circRNA, circGPC3 was experimentally demonstrated to up-regulate cell-cycle, migration and invasion. circGPC3 was found to act as a sponge of miR-378a-3p to regulate ASPM expression and modulate cell transformation. These 5 nodal circRNAs has potential to be good prognostic biomarkers with good prognostic performance. circGPC3 has great potential to be a promising non-invasive prognostic biomarker for early HCC. We have thus demonstrated the robustness of bioinformatically-predicted master circRNAs in clinically-relevant, circRNA-mRNA networks, underscoring the important roles that these identified deregulated key/master circRNAs play in HCC. Hepatocellular carcinoma (HCC) is one of the most common and lethal cancers worldwide. Here, we present a novel strategy to identify key circRNA signatures of clinically relevant co-expressed circRNA-mRNA networks in pertinent cancer-pathways that modulate prognosis of HCC patients, by integrating clinic-pathological features, circRNA and mRNA expression profiles. Through further integration with miRNA expression profiles, clinically relevant competing-endogenous-RNA (ceRNA) networks of circRNA-miRNA-mRNAs were constructed. At least five clinically relevant nodal-circRNAs, co-expressed with numerous genes, were identified from the circRNA-mRNA networks. These nodal circRNAs upregulated proliferation (except circRaly) and transformation in cells. The most upregulated nodal-circRNA, circGPC3, associated with higher-grade tumors and co-expressed with 33 genes, competes with 11 mRNAs for two shared miRNAs. circGPC3 was experimentally demonstrated to upregulate cell-cycle and migration/invasion in both transformed and non-transformed liver cell-lines. circGPC3 was further shown to act as a sponge of miR-378a-3p to regulate APSM (Abnormal spindle-like microcephaly associated) expression and modulate cell transformation. This study identifies 5 key nodal master circRNAs in a clinically relevant circRNA-centric network that are significantly associated with poorer prognosis of HCC patients and promotes tumorigenesis in cell-lines. The identification and characterization of these key circRNAs in clinically relevant circRNA-mRNA and ceRNA networks may facilitate the design of novel strategies targeting these important regulators for better HCC prognosis. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs), a class of small non-coding RNA molecules, are responsible for RNA silencing and post-transcriptional regulation of gene expression. They can mediate a fine-tuned crosstalk among coding and non-coding RNA molecules sharing miRNA response elements (MREs). In a suitable environment, both coding and non-coding RNA molecules can be targeted by the same miRNAs and can indirectly regulate each other by competing for them. These RNAs, otherwise known as competing endogenous RNAs (ceRNAs), lead to an additional post-transcriptional regulatory layer, where non-coding RNAs can find new significance. The miRNA-mediated interplay among different types of RNA molecules has been observed in many different contexts. The analyses of ceRNA networks in cancer and other pathologies, as well as in other physiological conditions, provide new opportunities for interpreting omics data for the field of personalized medicine. The development of novel computational tools, providing putative predictions of ceRNA interactions, is a rapidly growing field of interest. In this review, I discuss and present the current knowledge of the ceRNA mechanism and its implications in a broad spectrum of different pathologies, such as cardiovascular or autoimmune diseases, cancers and neurodegenerative disorders. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are small non-coding RNAs with a unique ability to regulate the transcriptomic profile by binding to complementary regulatory RNA sequences. The ability of miRNAs to enhance (proinflammatory miRNAs) or restrict (anti-inflammatory miRNAs) inflammatory signalling within the central nervous system is an area of ongoing research, particularly in the context of disorders that feature neuroinflammation, including neurodegenerative diseases (NDDs). Furthermore, the discovery of competing endogenous RNAs (ceRNAs) has led to an increase in the complexity of miRNA-mediated gene regulation, with a paradigm shift from a unidirectional to a bidirectional regulation, where miRNA acts as both a regulator and is regulated by ceRNAs. Increasing evidence has revealed that ceRNAs, including long non-coding RNAs, circular RNAs, and pseudogenes, can act as miRNA sponges to regulate neuroinflammation in NDDs within complex cross-talk regulatory machinery, which is referred to as ceRNA network (ceRNET). In this review, we discuss the role of miRNAs in neuroinflammatory regulation and the manner in which cellular and vesicular ceRNETs could influence neuroinflammatory dynamics in complex multifactorial diseases, such as NDDs. [ABSTRACT FROM AUTHOR]