HOXA transcript at the distal tip (HOTTIP), a lncRNA, induces cell proliferation and cancer progression. However, the expression and function of HOTTIP in renal cell carcinoma (RCC) were rarely reported. The role of the HOTTIP in RCC was explored in this study. HOTTIP expresses higher in RCC tissues than in normal tissues and indicates poor prognosis based on the TCGA database. The over- and low-expression HOTTIP cell line was established in this research to assess the oncogenic function of HOTTIP in RCC progression. Mechanistic analyses revealed that HOTTIP functioned as a competing endogenous RNA (ceRNA) for miR-506. RIP experiment and luciferase assay were performed to explore the mechanisms of the sponge between HOTTIP and miR-506. HOTTIP down-regulation attenuated cell proliferation, migration, and invasion, which could be rescued by miR-506 down-regulation. On the whole, this study revealed that the HOTTIP/miR-506 axis has a dominant impact on RCC progression and potentially provides a novel strategy for RCC diagnosis and therapy.

Insect sterility technology is gradually being applied to the control of lepidoptera pests, and the target gene for male sterility is the core of this technology. JMS is a mutant silkworm that exhibits male sterility, and to elucidate its formation mechanism, this study conducted a full transcriptome analysis of the testes of JMS and its wild-type silkworms 48 h after pupation, identifying 205 DElncRNAs, 913 mRNAs, and 92 DEmiRNAs. The KEGG pathway enrichment analysis of the DEmRNAs revealed that they were involved in the biosynthesis of amino acids and ECM-receptor interactions. Combined with ceRNA regulatory network KEGG analysis suggests that pathways from amino acid biosynthesis to hydrolytic processes of protein synthesis may play a crucial role in the formation of JMS mutant variants. Our study deepens our understanding of the regulatory network of male sterility genes in silkworms; it also provides a new perspective for insect sterility technology.

UNASSIGNED: Circular RNAs (circRNAs) have been shown to play critical roles in the initiation and progression of chronic glomerulonephritis (CGN), while their role from mesangial cells in contributing to the pathogenesis of CGN is rarely understood. Our study aims to explore the potential functions of mesangial cell-derived circRNAs using RNA sequencing (RNA-seq) and bioinformatics analysis.
UNASSIGNED: Mouse mesangial cells (MMCs) were stimulated by lipopolysaccharide (LPS) to establish an in vitro model of CGN. Pro-inflammatory cytokines and cell cycle stages were detected by Enzyme-linked immunosorbent assay (ELISA) and Flow Cytometry experiment, respectively. Subsequently, differentially expressed circRNAs (DE-circRNAs) were identified by RNA-seq. GEO microarrays were used to identify differentially expressed mRNAs (DE-mRNAs) between CGN and healthy populations. Weighted co-expression network analysis (WGCNA) was utilized to explore clinically significant modules of CGN. CircRNA-associated CeRNA networks were constructed by bioinformatics analysis. The hub mRNAs from CeRNA network were identified using LASSO algorithms. Furthermore, utilizing protein-protein interaction (PPI), gene ontology (GO), pathway enrichment (KEGG), and GSEA analyses to explore the potential biological function of target genes from CeRNA network. In addition, we investigated the relationships between immune cells and hub mRNAs from CeRNA network using CIBERSORT.
UNASSIGNED: The expression of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α was drastically increased in LPS-induced MMCs. The number of cells decreased significantly in the G1 phase but increased significantly in the S/G2 phase. A total of 6 DE-mRNAs were determined by RNA-seq, including 4 up-regulated circRNAs and 2 down-regulated circRNAs. WGCNA analysis identified 1747 DE-mRNAs of the turquoise module from CGN people in the GEO database. Then, the CeRNA networks, including 6 circRNAs, 38 miRNAs, and 80 mRNAs, were successfully constructed. The results of GO and KEGG analyses revealed that the target mRNAs were mainly enriched in immune, infection, and inflammation-related pathways. Furthermore, three hub mRNAs (BOC, MLST8, and HMGCS2) from the CeRNA network were screened using LASSO algorithms. GSEA analysis revealed that hub mRNAs were implicated in a great deal of immune system responses and inflammatory pathways, including IL-5 production, MAPK signaling pathway, and JAK-STAT signaling pathway. Moreover, according to an evaluation of immune infiltration, hub mRNAs have statistical correlations with neutrophils, plasma cells, monocytes, and follicular helper T cells.
UNASSIGNED: Our findings provide fundamental and novel insights for further investigations into the role of mesangial cell-derived circRNAs in CGN pathogenesis.

The incidence of tumors in the human digestive system is relatively high, including esophageal cancer, liver cancer, pancreatic cancer, gastric cancer and colorectal cancer. These malignancies arise from a complex interplay of environmental and genetic factors. Among them, long non‑coding RNAs (lncRNAs), which cannot be translated into proteins, serve an important role in the development, progression, migration and prognosis of tumors. Small nucleolar RNA host gene 16 (SNHG16) is a typical lncRNA, and its relationship with digestive system tumors has been widely explored. The prevailing hypothesis suggests that the principal molecular mechanism of SNHG16 in digestive system tumors involves it functioning as a competitive endogenous RNA that interacts with other proteins, regulates various genes and influences a downstream target molecule. The present review summarizes recent research on the relationship between SNHG16 and numerous types of digestive system cancer, encompassing its biological functions, underlying mechanisms and potential clinical implications. Furthermore, it outlines the association between SNHG16 expression and pertinent risk factors, such as smoking, infection and diet. The present review indicated the promise of SNHG16 as a potential biomarker and therapeutic target in human digestive system cancer.

BACKGROUND: Peripheral artery disease (PAD) is an ischemic disease with a rising incidence worldwide. The lncRNA H19 (H19) is enriched in endothelial progenitor cells (EPCs), and transplantation of pyroptosis-resistant H19-overexpressed EPCs (oe-H19-EPCs) may promote vasculogenesis and blood flow recovery in PAD, especially with critical limb ischemia (CLI).
METHODS: EPCs isolated from human peripheral blood was characterized using immunofluorescence and flow cytometry. Cell proliferation was determined with CCK8 and EdU assays. Cell migration was assessed by Transwell and wound healing assays. The angiogenic potential was evaluated using tube formation assay. The pyroptosis pathway-related protein in EPCs was detected by western blot. The binding sites of H19 and FADD on miR-107 were analyzed using Luciferase assays. In vivo, oe-H19-EPCs were transplanted into a mouse ischemic limb model, and blood flow was detected by laser Doppler imaging. The transcriptional landscape behind the therapeutic effects of oe-H19-EPCs on ischemic limbs were examined with whole transcriptome sequencing.
RESULTS: Overexpression of H19 in EPCs led to an increase in proliferation, migration, and tube formation abilities. These effects were mediated through pyroptosis pathway, which is regulated by the H19/miR-107/FADD axis. Transplantation of oe-H19-EPCs in a mouse ischemic limb model promoted vasculogenesis and blood flow recovery. Whole transcriptome sequencing indicated significant activation of vasculogenesis pathway in the ischemic limbs following treatment with oe-H19-EPCs.
CONCLUSIONS: Overexpression of H19 increases FADD level by competitively binding to miR-107, leading to enhanced proliferation, migration, vasculogenesis, and inhibition of pyroptosis in EPCs. These effects ultimately promote the recovery of blood flow in CLI.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) can lead to sudden cardiac death and life-threatening heart failure. Due to its high fatality rate and limited therapies, the pathogenesis and diagnosis biomarker of ARVC needs to be explored urgently. This study aimed to explore the lncRNA-miRNA-mRNA competitive endogenous RNA (ceRNA) network in ARVC. The mRNA and lncRNA expression datasets obtained from the Gene Expression Omnibus (GEO) database were used to analyze differentially expressed mRNA (DEM) and lncRNA (DElnc) between ARVC and non-failing controls. Differentially expressed miRNAs (DEmiRs) were obtained from the previous profiling work. Using starBase to predict targets of DEmiRs and intersecting with DEM and DElnc, a ceRNA network of lncRNA-miRNA-mRNA was constructed. The DEM and DElnc were validated by real-time quantitative PCR in human heart tissue. Protein-protein interaction network and weighted gene co-expression network analyses were used to identify hub genes. A logistic regression model for ARVC diagnostic prediction was established with the hub genes and their ceRNA pairs in the network. A total of 448 DEMs (282 upregulated and 166 downregulated) were identified, mainly enriched in extracellular matrix and fibrosis-related GO terms and KEGG pathways, such as extracellular matrix organization and collagen fibril organization. Four mRNAs and two lncRNAs, including COL1A1, COL5A1, FBN1, BGN, XIST, and LINC00173 identified through the ceRNA network, were validated by real-time quantitative PCR in human heart tissue and used to construct a logistic regression model. Good ARVC diagnostic prediction performance for the model was shown in both the training set and the validation set. The potential lncRNA-miRNA-mRNA regulatory network and logistic regression model established in our study may provide promising diagnostic methods for ARVC.

Epigenetic alterations of non-coding RNA (ncRNA) are pivotal in the continuous activation and differentiation of fibroblasts in keloid. However, the epigenetic mechanism of circRNA in keloid is still not clear yet. In this study, we aimed to investigate the interplay among differentially expressed circRNAs, miRNAs, and mRNAs during wound healing in keloid-prone individuals, construct a competing endogenous RNA (ceRNA) network, and gain an in-depth insight into the pathophysiological mechanisms underlying keloid development. Utilizing bioinformatic methods, we analyzed the expression profiles from the GSE113621 database. We identified 29 differentially expressed circRNAs (DEcircRNAs) in keloid-prone individuals during wound healing, from which we constructed 14 ceRNA networks. Subsequently, we validated the expression of predicted DEcircRNAs in keloid tissues and elucidated the ceRNA network involving circ_064002 and fibronectin-1 (FN1) through competing miR-30a/b-5p. Knocking down circ_064002 led to down-regulation of FN1 expression and various cellular functions in keloid-derived fibroblasts (KFs), including cell viability, migration, invasion, and repair capacity. Our study introduces a novel approach to explore the presence of DEcircRNAs and the ceRNA regulatory network during wound healing in keloid-prone individuals through in-depth mining of GEO data and also proves the epigenetic regulatory mechanism of circ_064002 in KFs. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive form of pulmonary fibrosis of unknown etiology. Despite ongoing research, there is currently no cure for this disease. Recent studies have highlighted the significance of competitive endogenous RNA (ceRNA) regulatory networks in IPF development. Therefore, this study investigated the ceRNA network associated with IPF pathogenesis. We obtained gene expression datasets (GSE32538, GSE32537, GSE47460, and GSE24206) from the Gene Expression Omnibus (GEO) database and analyzed them using bioinformatics tools to identify differentially expressed messenger RNAs (DEmRNAs), microRNAs (DEmiRNAs), and long non-coding RNAs (DElncRNA). For DEmRNAs, we conducted an enrichment analysis, constructed protein-protein interaction networks, and identified hub genes. Additionally, we predicted the target genes of differentially expressed mRNAs and their interacting long non-coding RNAs using various databases. Subsequently, we screened RNA molecules with ceRNA regulatory relations in the lncACTdb database based on the screening results. Furthermore, we performed disease and functional enrichment analyses and pathway prediction for miRNAs in the ceRNA network. We also validated the expression levels of candidate DEmRNAs through quantitative real-time reverse transcriptase polymerase chain reaction and analyzed the correlation between the expression of these candidate DEmRNAs and the percent predicted pre-bronchodilator forced vital capacity [%predicted FVC (pre-bd)]. We found that three ceRNA regulatory axes, specifically KCNQ1OT1/XIST/NEAT1-miR-20a-5p-ITGB8, XIST-miR-146b-5p/miR-31-5p- MMP16, and NEAT1-miR-31-5p-MMP16, have the potential to significantly affect IPF progression. Further examination of the underlying regulatory mechanisms within this network enhances our understanding of IPF pathogenesis and may aid in the identification of diagnostic biomarkers and therapeutic targets.

Aflatoxin B1 (AFB1) is an unavoidable environmental toxin. The accumulation of AFB1 and its metabolites in the liver poses a threat to both human and animal health. Curcumin exhibits anti-oxidative, anti-tumor, and anti-inflammatory properties. There is no report on the mechanism regarding how curcumin relived liver necroptosis in chickens induced by AFB1 based on the regulatory network of ceRNA. To explore this, we performed transmission electron microscopy and sequenced lncRNA and mRNA in chicken livers treated with AFB1 and/or curcumin for 28 d in vivo. We observed substantial alterations in the lncRNA and mRNA expression profiles within the chicken liver, indicating that curcumin can mitigate AFB1-induced necroptosis both in vivo and in vitro. Further analysis, including the establishment of an lncRNA-miRNA-mRNA network and the utilization of a dual luciferase reporter assay, revealed that LOC769044 acts as a competing endogenous RNA (ceRNA) for miR-1679. In addition, STAT1 was identified as a direct target of miR-1679. Modulating miR-1679 levels through overexpression, and silencing LOC769044 and STAT1, effectively reversed the necroptotic effects induced by AFB1, a reversal that was also observed with curcumin supplementation. In conclusion, our data demonstrate that curcumin alleviates AFB1-induced liver necroptosis through the LOC769044/miR-1679/STAT1 signaling axis. This study suggests that LOC769044 may serve as a novel therapeutic target for managing AFB1-mediated liver toxicity.

Circular RNAs (circRNAs) are a type of non-coding RNA (ncRNA) that possesses a unique single-stranded circular structure. They are primarily formed through alternative splicing of pre-mRNA (messenger RNA). The primary biological function of circRNAs is to regulate gene expression at both the transcriptional and post-transcriptional levels. Recent studies have increasingly demonstrated a close association between the dysregulation of circRNAs and the progression of diverse cancers, where they can function as either tumor suppressors or oncogenes. circWHSC1 (circNSD2) is a circular ncRNA that originates from the first 2 exons of the Wolf-Hirschhorn syndrome candidate gene (WHSC1). As Chen 2019 discovery that circWHSC1 (circNSD2) functions as a sponge for miRNAs and promotes cancer, this circRNA has garnered significant interest among researchers. circWHSC1 (circNSD2) has been found to be up-regulated in various malignant tumors, including nasopharyngeal carcinoma, lung cancer, breast cancer, liver cancer, colorectal cancer, ovarian cancer, cervical cancer, and endometrial cancer. It exerts its effects on cancer by either inhibiting or promoting the expression of related genes through direct or indirect pathways, ultimately affecting cancer proliferation, invasion, and prognosis. This article provides a comprehensive review and discussion of the biological roles of circWHSC1 (circNSD2) and its target genes in various cancers, as well as the latest research progress on related molecular biological regulatory mechanisms. Furthermore, the potential significance of circWHSC1 (circNSD2) in future clinical applications and transformations is thoroughly analyzed and discussed.