Search

Background: Human adipose-derived stem cells (hASCs) play an important role in regenerative medicine. Objective: Exploring the mechanism of Rg1 in the promotion of the proliferation and adipogenic differentiation of hASCs is important in regenerative medicine research. Methods: To observe ginsenoside Rg1 in promoting the proliferation and adipogenic differentiation of hASCs, Rg1 medium at different concentrations was established and tested using the cell counting kit-8 (CCK-8) assay, oil red O staining, alizarin red, and alcian blue. Compared to the control, differentially expressed genes (DEGs) were screened via DEG analysis, which was carried out in the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. To explore the relationship among mRNA, long non-coding RNA (lncRNA) and microRNA (miRNA), we constructed a competing endogenous RNA (ceRNA) network. Results: In this study, Rg1 was observed to promote the proliferation and adipogenic differentiation of hASCs. Additionally, enriched BPs and KEGG pathways may be involved in the promotion process, where FXR1 and Lnc-GAS5-AS1 were found to be regulatory factors. The regulatory network suggested that Rg1 could regulate the adipocytokine signaling pathway and IL−17 signaling pathway via FXR1 and Lnc-GAS5-AS1, which served as the mechanism encompassing the promotion of Rg1 on the proliferation and adipogenic differentiation of hASCs. Conclusion: A comprehensive transcriptional regulatory network related to the promotion ability of Rg1 was constructed, revealing mechanisms regarding Rg1’s promotion of the proliferation and adipogenic differentiation of hASCs. The present study provides a theoretical basis for optimizing the function of hASCs.

Background: This study intended to investigate the mechanisms underlying the epidermal growth factor receptor (EGFR) mutations in nonsmall cell lung cancer (NSCLC). Materials and Methods: Lung cancer tissue samples were collected from 20 patients with NSCLC (6 EGFR mutation types assigned into 2 categories and 14 EGFR wild types assigned to 4 categories). The samples were subjected to transcriptome sequencing, followed by identification of the differentially expressed mRNAs (DEMs), differentially expressed lncRNAs (DELs), and differentially expressed circRNAs (DECs) between the mutation and nonmutation groups. Function analysis and microRNA (miRNA) prediction for DEMs were performed. The correlations between long noncoding RNA (lncRNA)/circular RNA (circRNA) and messenger RNA (mRNA) were analyzed. In addition, the targeting lncRNA and circRNA of miRNA were predicted. Finally, competing endogenous RNA (ceRNA) network was constructed, and survival analysis for the mRNAs involved in the network was performed. Results: In total, 323 DEMs, 284 DELs, and 224 DECs were identified between EGFR mutation and nonmutation groups. The DEMs were significantly involved in gene ontology functions related to cilium morphogenesis and assembly. ceRNA networks were constructed based on the DEMs, DELs, DECs, and predicted miRNAs. Survival analysis showed that four genes in the ceRNA network, including ABCA3, ATL2, VAMP1, and APLN, were significantly associated with prognosis. The four genes were involved in several ceRNA pathways, including RP1-191J18/circ_000373/miR-520a-5p/ABCA3, RP5-1014D13/let-7i-5p/ATL2, circ_000373/miR-1293/VAMP1, and RP1-191J18/circ_000373/miR-378a-5p/APLN. Conclusion: EGFR mutations in NSCLC may be associated with cilium dysfunction and complex ceRNA regulatory mechanisms. The key RNAs in the ceRNA network may be used as promising biomarkers for predicting EGFR mutations in NSCLC.

Sepsis is a severe medical condition distinguished by immune systematic dysfunction and multiple organic injury, or even failure, resulting from an acute systemic inflammatory response. Acute liver injury (ALI) could be considered as a notable inflammatory outcome of sepsis. Studies have demonstrated the essential roles played by long non-coding RNAs (lncRNAs) in mediating the processes of various diseases, including their ability to engage in interactions with microRNAs (miRNAs) as complexes of competing endogenous RNA (ceRNA) to modulate signaling pathways. In this study, a newly discovered lncRNA, named 220, was identified to function in regulating autophagy and apoptosis in Kupffer cells treated with lipopolysaccharide (LPS). This was achieved through sponging miR-5101 as a ceRNA complex, as identified via high-throughput sequencing. The expression of 220 was found to be significantly different in the hepatic tissues of endotoxemic mice that were treated with LPS for 8 h, ultimately modulating the ALI process. Our studies have collectively demonstrated that 220 is a novel regulator that acts on LPS-induced autophagy and apoptosis in Kupffer cells, thereby mediating the ALI process induced by LPS. Furthermore, the validation of our findings using clinical databases suggests that 220 could potentially serve as a molecular target of clinical, diagnostic, and therapeutic significance in septic liver injury.

Valgus-valgus deformity (VVD) is a common leg deformity in broilers with inward or outward deviation of the tibiotarsus and tarsometatarsus. The competing endogenous RNA (ceRNA) network plays an essential role in the study of leg disease. However, its role in the etiology and pathogenesis of VVD remains unclear. Here, based on case (VVD) and control (normal) group design, we performed analyses of differentially expressed circRNAs (DEcircRNAs), differentially expressed miRNAs (DEmiRNAs) and differentially expressed mRNAs (DEmRNAs). Transcriptome data derived 86 DEcircRNAs, 13 DEmiRNAs and 410 DEmRNAs. Functional analysis showed that DEmRNAs were significantly enriched in cell cycle, apoptosis, ECM-receptor interaction, FoxO signaling pathway and protein processing synthesis. DEcirc/miRNA-associated DEmRNAs were associated with skeletal and muscle growth and development pathways, including mTOR, Wnt, and VEGF signaling pathways. Subsequently, a circRNA–miRNA–mRNA regulatory network was constructed based on the ceRNA hypothesis, including 8 circRNAs, 6 miRNAs, and 31 mRNAs, which were significantly enriched in the skeletal developmental pathway. Finally, two key mRNAs (CDC20 and CTNNB1) and their regulatory axes were screened by the PPI network and cytohubba. The expression levels of CDC20 and CTNNB1 in cartilage and seven other tissues were also quantified by qPCR. In conclusion, we analyzed the functions of DEmRNA, DEcircRNA and DEmiRNA and constructed the hub ceRNA regulatory axis, and obtained two hub genes, CDC20 and CTNNB1. The study more deeply explored the etiology and pathogenesis of VVD and lays the foundation for further study of the role of the ceRNA network on skeletal development.

BACKGROUND: Colorectal cancer (CRC), one of the most common human malignancies, is a leading cause of the cancer-related mortality. 5-FU is a first-line chemotherapeutic agent against CRC. Although CRC patients responded to 5-FU therapy initially, a part of patients succumbed to CRC due to the acquired drug resistance. Thus, investigating molecular mechanisms underlying chemoresistance will contribute to developing novel strategies against colorectal cancer. OBJECTIVE: Accumulation evidence revealed pivotal roles of long non-coding RNAs (lncRNAs) in tumorigenesis and chemoresistance of CRC. However, the precise roles and molecular mechanisms of lncRNA-HCG11 in CRC remain unclear. This study aimed to investigate the biological roles and underlying mechanisms of HCG11 as well as its molecular targets in regulating the cellular metabolism processes, which facilitate the chemoresistance of CRC. METHODS AND RESULTS: This study uncovers that HCG11 was significantly upregulated in CRC tumors tissues and cell lines. Moreover, HCG11 was elevated in 5-FU resistant CRC tumors. Silencing HCG11 inhibited colon cancer cell proliferation, migration, invasion and glucose metabolism and sensitized CRC cells to 5-FU. In addition, we detected increased HCG11 expression level and glucose metabolism in the established 5-FU resistant CRC cell line (DLD-1 5-FU Res). Furthermore, microRNA-microArray, RNA pull-down and luciferase assays demonstrated that HCG11 inhibited miR-144-3p which displays suppressive roles in colon cancer via sponging it to form a ceRNA network. We identified pyruvate dehydrogenase kinase 4 (PDK4), which is a glucose metabolism key enzyme, was directly targeted by miR-144-3p in CRC cells. Rescue studies validated that the miR-144-3p-inhibited glucose metabolism and 5-FU sensitization were through targeting PDK4. Finally, restoration of miR-144-3p in HCG11-overexpressing DLD-1 5-FU resistant cells successfully overcame the HCG11-faciliated 5-FU resistance via targeting PDK4. CONCLUSION: In summary, this study reveals critical roles and molecular mechanisms of the HCG11-mediated 5-FU resistance through modulating the miR-144-3p-PDK4-glucose metabolism pathway in CRC.

BACKGROUND: The disorder of LINC01207 has a significant regulatory effect on cancers, nevertheless its role in non-small cell lung cancer (NSCLC) have not been illustrated. This study investigated the regulatory effect of LINC01207 on NSCLC and clarify its molecular mechanism. METHODS: Bioinformatics analysis was used to find the target lncRNA, miRNA and mRNA. LncBase and TargetScan databases predicted the relationship between LINC01207, miR-525-5p and ARHGAP11A. Dual-luciferase reporter gene assay and RNA binding protein immunoprecipitation assay were used to verify the binding relationship between genes. Fluorescence in situ hybridization assay was used to localize the expression of LINC01207 in NSCLC tissue. qRT-PCR and Western blot assays were used to measure the expression of LINC01207, miR-525-5p and ARHGAP11A. CCK-8 assay, Transwell assay and flow cytometry assay were used to detect NSCLC cell abilities. Mouse xenograft models further determined the effect of LINC01207 on the growth of NSCLC in vivo. RESULTS: LINC01207 was up-regulated in NSCLC tissue and cells, which was mainly localized in the cytoplasm. LINC01207 knockdown could inhibit the proliferation, migration and invasion of cancer cells and induce cell apoptosis. In addition, silencing LINC01207 could suppress tumor growth in vivo. LINC01207 could sponge and inhibit the expression of miR-525-5p in NSCLC cells, and inhibiting LINC01207 and miR-525-5p simultaneously could reverse the effect of miR-525-5p on the progression of NSCLC cells. Further study on downstream target genes showed that miR-525-5p could restrain the expression of ARHGAP11A, and then affect the progression of NSCLC. LINC01207 acting as a competing endogenous RNA (ceRNA) could regulate the expression of ARHGAP11A by competitively binding with miR-525-5p. CONCLUSION: LINC01207 regulates the progression of NSCLC by regulating the miR-525-5p/ARHGAP11A axis as a ceRNA and plays a carcinogenic role. In conclusion, our study elucidates the mechanism of LINC01207 regulating the progression of NSCLC, and provides a new idea for the diagnosis and treatment of NSCLC guided by lncRNA.

Tea leaf spot, caused by Didymella segeticola (Q. Chen) Q. Chen, Crous & L. Cai, is an important disease, which negatively affects the productivity and the quality of tea leaves. During infection by the pathogen, competing endogenous RNAs (ceRNAs) from tea leaves could contribute to achieving pathogenicity. In this study, circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs), constituting ceRNAs, which share binding sites on microRNAs (miRNAs), and messenger RNAs (mRNAs), from infected and uninfected leaves of tea (Camellia sinensis cv. Fuding-dabaicha) were sequenced and analyzed, and the identity and expression levels of the target genes of miRNA-mRNA and miRNA-lncRNA/circRNA were predicted. Analysis indicated that ten mRNAs were bound by 18 miRNAs, 66 lncRNAs were bound by 40 miRNAs, and 29 circRNAs were bound by 17 miRNAs, respectively. For the regulation modes of ceRNAs, five ceRNA pairs were identified by the correlation analysis of lncRNA-miRNA-mRNA. For instance, expression of the xyloglucan endotransglycosylase (XET) gene in infected leaves was down-regulated at the level of mRNA through miRNA PC-5p-3511474_3 binding with lncRNA TEA024202.1:MSTRG.37074.1. Gene annotation indicated that expression of this gene was significantly enriched in cell wall biogenesis and in the pathway of plant hormone signal transduction. The functional analysis of ceRNAs isolated from infected tea leaves will provide a valuable resource for future research on D. segeticola pathogenicity.

Background: Cognitive impairment is a common neurocognitive disorder that affects millions of worldwide people’s health,related tofolate deficiency. Objective: The present study aimed to investigate the lncRNA-mRNA functional networks associated with cognitive impairment in folate-deficient mice and elucidate their possible molecular mechanisms. Methods: We downloaded the gene expression profile (GSE148126) of lncRNAs and mRNAs from NCBI Gene Expression Omnibus (GEO) database. Four groups of mouse hippocampi were analyzed, including 4 months (4mo) and 18 months (18mo) of folic acid (FA) deficiency/supplementation. The differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) were identified using gplots and heatmap packages. The functions of the DEmRNAs were evaluated using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The hub genes wereidentified by CytoHubba plugins of Cytoscape, and protein-protein interaction (PPI) network of deregulated mRNAs was performed using STRING database. Finally, lncRNA-mRNA co-expression and competitive endogenous RNA (ceRNA) network analyses were constructed. Results: In total, we screened 67 lncRNAs with 211 mRNAs, and 89 lncRNAs with 229 mRNAs were differentially expressed in 4mo_FAand 18mo_FA deficient mice, respectively. GO analyses indicated that DEmRNAs were highly related to terms involved in binding and biological regulation. KEGG pathway analyses demonstrated that these genes were significantly enriched for Renin secretion, Pancreatic secretion and AMPK signaling pathways in 18mo_FA deficiency group. Subsequently, the top 5 hub genes werescreened from the PPI network, which may be key genes with the progression of folate deficiency. Upon the lncRNA-mRNA co-expression network analysis, we identified the top 10 lncRNAs having the maximum number of connections with related mRNAs. Finally, a ceRNA network was constructed for DE lncRNAs and DEmRNAs, and several pivotal miRNAs were predicted. Conclusions: This study identified the lncRNA-mRNA expression profiles and functional networks associated with cognitive impairment in folate-deficient mice, which provided support for the possible mechanisms and therapy for this disease.

Colorectal cancer (CRC) is the third main cause of cancer-relevant deaths worldwide, and its incidence has increased in recent decades. Previous studies have indicated that certain long noncoding RNAs (lncRNAs) have regulatory roles in tumor occurrence and progression. Often, lncRNAs are competitive endogenous RNAs that sponge microRNAs to up-regulate mRNAs. Here, we examined the role of a novel lncRNA gamma-butyrobetaine hydroxylase 1 antisense RNA 1 (BBOX1-AS1) in CRC. We observed that BBOX1-AS1 is overexpressed in CRC cell lines, and BBOX1-AS1 knockdown enhances cell proliferation, migration and invasion while reducing cell apoptosis. miR-361-3p is present at a low level in CRC and is negatively modified by BBOX1-AS1. Moreover, miR-361-3p was validated to be targeted by BBOX1-AS1. Src homology 2 B adaptor protein 1 (SH2B1) was notably upregulated in CRC cell lines and was identified as a downstream gene of miR-361-3p. In addition, we found that miR-361-3p amplification can suppress the expression of SH2B1. Finally, data from rescue assays suggested that overexpression of SH2B1 counteracted BBOX1-AS1 silencing-mediated inhibition of CRC progression. In conclusion, BBOX1-AS1 promotes CRC progression by sponging hsa-miR-361-3p and up-regulating SH2B1.

Cardiac hypertrophy is a common cardiovascular disease that is found worldwide and is characterized by heart enlargement, eventually resulting in heart failure. Exploring the regulatory mechanism of cardiac hypertrophy is beneficial for understanding its pathogenesis and treatment. In our study, we have showed TINCR was downregulated and miR-211-3p was upregulated in TAC- or Ang II-induced models of cardiac hypertrophy. Dual luciferase and RIP assays revealed that TINCR served as a competitive endogenous RNA (ceRNA) for miR-211-3p. Then, we observed that knockdown of miR-211-3p alleviated TAC- or Ang II-induced cardiac hypertrophy both in vivo and in vitro. Mechanistically, we demonstrated that miR-211-3p directly targeted VEGFB and thus regulated the expression of SDF-1α and CXCR4. Rescue assays further confirmed that TINCR suppressed the progression of cardiac hypertrophy by competitively binding to miR-211-3p, thereby enhancing the expression of VEGFB and activating the VEGFB-SDF-1α- CXCR4 signal. Furthermore, overexpression of TINCR suppressed TAC-induced cardiac hypertrophy in vivo by targeting miR-211-3p-VEGFB-SDF-1α- CXCR4 signalling. In conclusion, our research suggests that LncRNA TINCR improves cardiac hypertrophy by targeting miR-211-3p, thus relieving its suppressive effects on the VEGFB-SDF-1α-CXCR4 signalling axis. TINCR and miR-211-3p might act as therapeutic targets for the treatment of cardiac hypertrophy.

The prognosis for cervical cancer (CC) patients with lymph node metastasis (LNM) is extremely poor. Lipid droplets (LDs) have a pivotal role in promoting tumor metastasis. The crosstalk mechanism between LDs and LNM modulated in CC remains largely unknown.This study aimed to construct a miRNA-dependent progonostic model for CC patients and investigate whether miR-532-5p has a biological impact on LNM by regualting LDs accumulation.LASSO-Cox regression was applied to establish a prognostic prediction model. miR-532-5p had the lowest P-value in RNA expression (P 0.001) and prognostic prediction (P 0.0001) and was selected for further study. The functional role of the prognostic miR-532-5p-correlated competing endogenous RNA (ceRNA) network was investigated to clarify the crosstalk between LDs and LNM. The underlying mechanism was determined using site-directed mutagenesis, dual luciferase reporter assays, RNA immunoprecipitation assays, and rescue experiments. A xenograft LNM model was established to evaluate the effect of miR-532-5p and orlistat combination therapy on tumor growth and LNM.A novel 5-miRNAs prognostic signature was constructed to better predict the prognosis of CC patient. Further study demonstrated that miR-532-5p inhibited epithelial-mesenchymal transition and lymphangiogenesis by regulating LDs accumulation. Interestingly, we also found that LDs accumulation promoted cell metastasis in vitro. Mechanistically, we demonstrated a miR-532-5p-correlated ceRNA network in which LINC01410 was bound directly to miR-532-5p and effectively functioned as miR-532-5p sponge to disinhibit its target gene-fatty acid synthase (Our findings highlight a LD accumulation-dependent mechanism of miR-532-5p-modulated LNM and support treatment with miR-532-5p/orlistat as novel strategy for treating patients with LNM in CC.

Colorectal cancer (CRC) is the third leading cause of cancer-related death worldwide. Dysregulation of circular RNAs (circRNAs) appears to be a critical factor in CRC progression. However, mechanistic studies delineating the role of circRNAs in CRC remain limited. In this study, qRT-PCR and western blot assays were used to measure the expression of genes and proteins. Migration, invasion, proliferation, and apoptosis were examined by wound-healing, transwell, CCK-8, colony formation, and flow cytometry assays, respectively. Molecular interactions were validated by a dual-luciferase report system. A xenograft animal model was established to examine in vivo tumor growth and lung metastasis. Our data indicated that circN4BP2L2 expression was increased in CRC tissues and cell lines. Notably, inhibition of circN4BP2L2 effectively inhibited proliferation, migration, and invasion of LoVo cells, and inhibited tumor growth and metastasis in vivo, whereas the forced expression of circN4BP2L2 facilitated the proliferation, migration, and invasion of HT-29 cells. Mechanistic studies revealed that circN4BP2L2 acted as a molecular sponge of miR-340-5p to competitively promote CXCR4 expression. Furthermore, inhibition of miR-340-5p reversed the anti-cancer effects of circN4BP2L2 or CXCR4 silencing. Our data indicated an oncogenic role of circN4BP2L2 in CRC via regulation of the miR-340-5p/CXCR4 axis, which may be a promising biomarker and target for CRC treatment. This study determined that circN4BP2L2 acts as an oncogene that promotes tumor growth and metastasis of colorectal cancer (CRC) by regulating the miR-340-5p/CXCR4 axis. The authors reveal a novel mechanism for the ceRNA regulatory network in CRC progression and identify a potential therapeutic target for CRC treatment.

Circular RNAs (circRNAs) are noncoding RNAs that form covalently closed loop structures. CircRNAs are dysregulated in cancer and play key roles in tumorigenesis, diagnosis, and tumor therapy. CircRNAs function as competing endogenous RNAs or microRNA sponges that regulate transcription and splicing, binding to proteins, and translation. CircRNAs may serve as novel biomarkers for cancer diagnosis, and they show potential as therapeutic targets in cancers including breast cancer (BC). In women, BC is the most common malignant tumor worldwide and the second leading cause of cancer death. Although evidence indicates that circRNAs play a critical role in BC, the mechanisms regulating the function of circRNAs in BC remain poorly understood. Here, we provide literature review aiming to clarify the role of circRNAs in BC and summarize the latest research. We provide a systematic overview of the biogenesis and biological functions of circRNAs, elaborate on the functional roles of circRNAs in BC, and highlight the value of circRNAs as diagnostic and therapeutic targets in BC.

Intracerebral hemorrhage (ICH) is a leading cause of death and disability worldwide. This study aimed to examine the involvement of long non-coding RNAs (lncRNAs), a group of non-coding transcripts, in ICH as potential biomarkers. An expression profile of patients with ICH using four contralateral grey matter controls (GM) and four contralateral white matter controls (WM) was downloaded from the Gene Expression Omnibus (GEO) database. Co-expressed lncRNAs and mRNAs were selected to create competing endogenous RNA (ceRNA) networks. Key lncRNAs were identified in ceRNA networks, which were validated through Real-time qPCR (RT-qPCR) with peripheral blood samples from patients with ICH. A total of 49 differentially expressed lncRNAs were discovered in different brain regions. The ceRNA network in GM included 9 lncRNAs, 40 mRNAs, and 20 microRNAs (miRNAs), while the one in WM covered 6 lncRNAs, 25 mRNAs, and 14 miRNAs. Six hub lncRNAs were observed and RT-qPCR results showed that LY86-AS1, DLX6-AS1, RRN3P2, and CRNDE were down-regulated, while HCP5 and MIAT were up-regulated in patients with ICH. Receiver Operating Characteristic (ROC) assessments demonstrated the diagnostic value of these lncRNAs. Our findings highlight the potential roles of lncRNA in ICH pathogenesis. Moreover, the hub lncRNAs discovered here might become novel biomarkers and promising targets for ICH drug development.

background: Glioblastoma Multiform (GBM) is the primary malignancy with the highest incidence and worst prognosis in the adult CNS. Circular RNAs (circRNAs) are a novel and widely diverse class of endogenous non-coding RNAs that can promote or inhibit gliomagenesis. Our study aimed to explore the role of circASPM in GBM and its molecular mechanism.Methods: Levels of circASPM, miR-130b-3p and E2F1 were determined by quantitative real-time PCR (qRT-PCR) or western blotting assay. MTS, Edu, neurospheres formation and extreme limiting dilution assays were used to detect the tumorigenesis and proliferation of GSCs in vitro. The interactions between miR-130b-3p and circASPM or E2F1 was demonstrated via qPCR, western blotting, dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Xenograft experiments was used to analyze tumor growth in vivo.Results: CircASPM was overexpressed in GBM and could promote the tumorigenesis and proliferation of GSCs both in vitro and in vivo. Mechanistically, circASPM up-regulated the expression of E2F1 in GSCs via miR-130b-3p sponging. We furtherly demonstrated that circAPSM could promote the GSCs proliferation via E2F1 up-regulating. Therefore, our study identified a novel circRNA and its possible mechanism in the development and tumorigenesis of GBM.Conclusions: CircASPM can promote GBM progression via regulating miR-130b-3p/E2F1 axis, suggesting that circAPSM could provide an effective biomarker for GBM diagnosis and prognostic evaluation and possibly being used for molecular targeted therapy.

Long noncoding RNAs (lncRNAs) have been shown to be closely related to cancer progression and therapy. However, the clinical significance of lncRNAs and the mechanisms by which they function in glioma are largely unknown. In this study, using online data sets combined with collected clinical glioma tissues, we determined that the lncRNA KB-1460A1.5 is downregulated and positively correlated with prognosis in glioma. Functional experiments showed that overexpression of KB-1460A1.5 inhibits glioma cell proliferation, migration and invasion in vitro and in vivo, while downregulation of KB-1460A1.5 has the opposite effects. Mechanistically, tandem mass tag (TMT)-based quantitative proteomic analysis revealed that KB-1460A1.5 preferentially affects the Akt/TSC1/mTOR pathway. KB-1460A1.5 was found to function as a competing endogenous RNA (ceRNA) to regulate the expression of TSC1, a key regulatory component of the mTOR pathway, by sponging miR-130a-3p in glioma cells. Furthermore, our data demonstrate that the mTOR pathway regulates the expression of the transcription factor Yin Yang 1 (YY1), which in turn binds directly to the KB-1460A1.5 promoter and affects the expression of KB-1460A1.5. Untargeted metabolomics and quantitative real-time PCR (qRT-PCR) analysis further confirmed the effects of KB-1460A1.5 on amino acid metabolism. In conclusion, this study revealed that lncRNA KB-1460A1.5 inhibits glioma tumorigenesis via miR-130a-3p/TSC1/mTOR/YY1 feedback loop.

LncRNAs are widely involved in various biological processes of plants. Recent evidences indicated that lncRNAs could act as competing endogenous RNAs (ceRNAs) to adsorb complementary miRNAs in a type of target mimicry, thereby indirectly regulating the target genes of miRNAs. In this study, a lncRNA, lncRNA08489 was identified to be the ceRNA of miR482e-3p in tomato plants. The expression patterns of lncRNA08489 and miR482e-3p showed opposite trends after tomato plants infected with Phytophthora infestans. In tomato leaves overexpressing lncRNA08489 (OE08489), the expression level of miR482e-3p decreased and its target gene, NBS-LRR increased. After infection with P. infestans, the resistance of OE08489 plants was stronger than that of the wild type, and the reactive oxygen species (ROS) scavenging ability of OE08489 plants was significantly improved. Taken together, these results indicated that lncRNA08489 acted as a ceRNA to decoy miR482e-3p and regulate the expression of NBS-LRR to enhance tomato resistance through ROS-scavenging system.

Long intergenic nonprotein-coding RNA 1703 (LINC01703) has diagnostic significance in lung adenocarcinoma. However, its specific roles in non-small cell lung cancer (NSCLC) and downstream mechanisms have not been investigated. In the current study, we characterized the role of LINC01703 in NSCLC malignancy and elucidated its detailed mechanism of action. LINC01703 expression was measured by qRT-PCR. The regulatory effects of LINC01703 on the malignancy of NSCLC cells were assessed by multiple functional experiments. The targeted interaction was confirmed by RNA immunoprecipitation and luciferase reporter assays. Herein, overexpression of LINC01703 in NSCLC was indicated in the TCGA database and further proven in our cohort. Functional studies revealed that knocking down LINC01703 repressed cell proliferation, colony formation, migration, and invasion in vitro, which was accompanied by the induction of apoptosis. The tumor growth of LINC01703-silenced cells was also inhibited in vivo. Mechanistic analyses revealed that LINC01703 functioned as a competing endogenous RNA for microRNA-605-3p (miR-605-3p) in NSCLC cells, which thereby upregulated the miR-605-3p target metastasis associated with colon cancer 1 (MACC1). Rescue experiments highlighted that the regulatory actions of LINC01703 ablation on NSCLC cells were abolished in response to miR-605-3p downregulation or MACC1 overexpression. In conclusion, LINC01703 enhanced the aggressiveness of NSCLC cells by altering miR-605-3p/MACC1. Our work suggests the therapeutic potential of LINC01703/miR-605-3p/MACC1 in NSCLC.

Clear cell renal cell carcinoma (ccRCC) is a fatal cancer of the urinary system. Long non-coding RNAs (lncRNAs) act as competitive endogenous RNAs (ceRNAs) involving the ccRCC progression. However, the relationship between the ceRNA network and immune signature is largely unknown. In this study, the ccRCC-related gene expression profiles retrieved from the TCGA database were used first to identify the differentially expressed genes through differential gene expression analysis and weighted gene co-expression network analysis. The interaction among differentially expressed lncRNAs, miRNAs, and mRNAs were matched using public databases. As a result, a ceRNA network was developed that contained 144 lncRNAs, 23 miRNAs, as well as 62 mRNAs. Four of 144 lncRNAs including LINC00943, SRD5A3-AS1, LINC02345, and U62317.3 were identified through LASSO regression and Cox regression analyses, and were used to create a prognostic risk model. Then, the ccRCC samples were divided into the high- and low-risk groups depending on their risk scores. ROC curves, Kaplan-Meier survival analysis, and the survival risk plots indicated that the predictive performance of our developed risk model was accurate. Moreover, the CIBERSORT algorithm was used to measure the infiltration levels of immune cells in the ccRCC samples. The further genomic analysis illustrated a positive correlation between most immune checkpoint blockade-related genes and the risk score. In conclusion, the present findings effectually contribute to the comprehensive understanding of the ccRCC pathogenesis, and may offer a reference for developing novel therapeutic and prognostic biomarkers.

Spinal cord injury (SCI) is a traumatic disease resulting in neuronal injury. circRNAs are closely associated with human diseases. Nevertheless, the potential mechanism by which circRNAs impact SCI remains to be elucidated. The aim of this study was to investigate the regulatory roles of Circular RNAs (circRNAs) in SCI. The SCI mouse model and integrated bioinformatics analysis were used to identify the differentially expressed genes (DEGs). Functional enrichment analysis was conducted to study the related pathways. The circRNA-mediated ceRNA network and subnetwork was constructed based on circMir, TargetScan and miRanda. qRT–PCR, ELISA, flow cytometry, and luciferase reporter assays were carried out to validate the role of circ_0014637 (circ-Usp10) and microRNA(miR)-152-5p /CD84 in microglia. In all, 23 DE-circRNAs, 127 DE-miRNAs and 1327 DE-mRNAs were identified. We integrated these DEGs to construct a circRNA-miRNA-mRNA network. The circ-Usp10/miR-152-5p/CD84 axis was found to function in microglial activation. We also found that circ-Usp10 inhibited the secretion of proinflammatory factors in microglial BV2 cells. In addition, silencing circ-Usp10 significantly reduced the death of the neuronal cell line HT22. Taken together, we concluded that circ-Usp10 may function as a competing endogenous RNA (ceRNA) to promote microglial activation and induce neuronal death by targeting miR-152-5p/CD84. The circ-Usp10 may be a diagnostic biomarker and potential target for SCI therapy.

Breast cancer (BC) is the most common cancer among women. LINC00675 and miR-513b-5p has been reported to be abnormally expressed in multiple types of cancers and modulate malignant phenotypes of cancer cells. However, to date, the functional role and underlying regulatory mechanism of LINC00675 and miR-513b-5p in BC remains largely unknown. Here, we found that LINC00675 was significantly downregulated in BC tissues and cell lines. Decrease of LINC00675 expression associated with higher tumor grade, lymphovascular invasion and shorter survival in BC patients. Functional experiments demonstrated that overexpression of LINC00675 suppressed BC cell proliferation, migration and invasion, whereas depletion of LINC00675 exerted opposite effects. Mechanistically, LINC00675 functioned as a competing endogenous RNA (ceRNA) to interact with miR-513b-5p and suppress its expression. Moreover, METTL3 increased the m6A methylation of LINC00675, which enhanced the association between LINC00675 and miR-513b-5p. Collectively, the central findings of our study suggest that LINC00675 represses BC progression through the inhibition of miR-513b-5p in a m6A-dependent manner.

Unexplained recurrent spontaneous abortion (URSA) is one of the most intractable clinical challenges in reproduction. As a specific type of endogenous non-coding RNA, circular RNAs (circRNAs) have great pre-clinical diagnostic and therapeutic values in diseases. Recently, thousands of circRNAs were detected in human pre-implantation embryos, indicating that circRNAs potentially have important regulatory functions. However, the roles of circRNAs in URSA remain largely unknown. In this study, we elucidated deregulated circRNA expression and distinct competing endogenous RNA (ceRNA) networks by comparing URSA placental villus with that of patients with normal pregnancy using microarrays. We characterized a distinct circRNA, circRNA-0050703, which is downregulated in URSA placental villus (thus we named it circRNA-DURSA). Silencing of circRNA-DURSA results in trophoblast cell apoptosis in vitro. Furthermore, mechanistic dissection revealed that circRNA-DURSA exerts its effects by competitively binding to miR-760, which post-transcriptionally targets HIST1H2BE. Additionally, after circRNA-DURSA silencing in vivo, the numbers of implanted embryos decreased significantly. These results reveal the regulatory roles of circRNA-DURSA in trophoblasts and identified a distinct circRNA-DURSA/miR-760/HIST1H2BE axis as potentially important diagnostic and therapeutic targets for URSA treatment., Graphical abstract, circRNAs have been found to have great pre-clinical diagnostic and therapeutic values in various diseases. In this study, we characterized a novel circRNA, circRNA-DURSA, which is downregulated in URSA placental villus and exerts regulatory roles through the circRNA-DURSA/miR-760/HIST1H2BE axis in trophoblasts. These findings may provide novel mechanistic and clinical insights for future management of URSA.

The competing endogenous RNA (ceRNA) activity of circular RNAs (circRNAs) has been implicated in the development of gastric cancer. Here, we sought to explore the ceRNA function of circRNA Jupiter microtubule associated homolog 1 (circ_HN1) in gastric tumorigenesis. Circ_HN1, microRNA (miR)-628-5p, and NT5E expression levels were quantified by qRT-PCR and western blot. Dual-luciferase reporter assays were used to assess the direct relationship between miR-628-5p and circ_HN1 or NT5E. Our data showed that circ_HN1 expression was enhanced in human gastric cancer. Depletion of circ_HN1 impeded cell proliferation, spheroid formation, invasion, and migration and promoted apoptosis in vitro, as well as diminished tumor growth in vivo. NT5E was a downstream effector of circ_HN1 function. NT5E was targeted and inhibited by miR-628-5p through the perfect complementary site in NT5E 3ʹUTR, and circ_HN1 affected NT5E expression through miR-628-5p competition. Moreover, depletion of miR-628-5p reversed the effects of circ_HN1 silencing on regulating cell functional behaviors. Our findings identify a novel ceRNA network, the circ_HN1/miR-628-5p/NT5E axis, for the oncogenic activity of circ_HN1 in gastric cancer, highlighting circ_HN1 inhibition as a promising targeted treatment against gastric cancer.

Aluminum is a known neurotoxin that can induce Aβ deposition and abnormal phosphorylation of tau protein, leading to Alzheimer disease (AD)-like damages such as neuronal damage and decreased learning and memory functions. In this study, we constructed a rat model of subchronic aluminum maltol exposure, and the whole-transcriptome sequencing was performed on the hippocampus of the control group and the middle-dose group. A total of 167 miRNAs, 37 lncRNAs, 256 mRNAs, and 64 circRNAs expression changed. The Kyoto Encyclopedia of Genes and Genomes showed that PI3K/AKT pathway was the most enriched pathway of DEGs, and IRS1 was the core molecule in the PPI network. circRNA/lncRNA-miRNA-mRNA networks of all DEGs, DEGs in the PI3K/AKT pathway, and IRS1 were constructed by Cytoscape. Molecular experiment results showed that aluminum inhibited the IRS1/PI3K/AKT pathway and increased the content of Aβ and tau. In addition, we also constructed an AAV intervention rat model, proving that inhibition of miR-96-5p expression might resist aluminum-induced injury by upregulating expression of IRS1. In general, these results suggest that the ceRNA networks are involved in the neurotoxic process of aluminum, providing a new strategy for studying the toxicity mechanism of aluminum and finding biological targets for the prevention and treatment of AD., Graphical Abstract, He et al. performed whole-transcriptome sequencing and verification on the hippocampus of aluminum-exposed rats, suggesting that the ceRNA network is involved in the neurotoxic process of aluminum, providing a new strategy for studying the neurotoxicity of aluminum and finding biological targets for the prevention and treatment of AD.

The circRNAs, a new subclass of non-coding RNAs that are catalyzed by RNA-binding proteins (RBPs), have been reported to be associated with the progression of multiple types of cancer. We previously discovered that heterogeneous nuclear ribonucleoprotein L (HnRNP-L), a multi-functional RBP, is associated with pro-proliferation and anti-apoptosis activities in prostate tumor cells. In this study, we aim to establish the biological relevance of circCSPP1 (a newly discovered signature circRNA in prostate cancer [PCa]) and HnRNP-L to prostate cancer progression. First, we demonstrated that circCSPP1 expression was higher in prostate cancer tissues than in benign tissues and higher in prostate cancer cells than in benign cells. Then, the in vitro gain- and loss-of-function experiments showed that the circCSPP1 expression in prostate cancer cells was regulated by HnRNP-L, and the increased circCSPP1 significantly induced autophagy, which led to an enhanced potential in proliferation, migration, and invasion of prostate cancer cells. These results were consistent with the in vivo experiment where increased or decreased circCSPP1 was associated with higher or slower growth rate in grafted tumors. Finally, we demonstrated the potential competing endogenous RNA network, involving circCSPP1, miR-520h, and early growth response factor 1 (EGR1), in prostate cancer cells, which may play an important role in prostate cancer progression. Our study indicated that the increase in circCSPP1 in prostate cancer, which may be catalyzed by HnRNP-L, can induce cellular autophagy through the circCSPP1-miR-520h-EGR1 axis, leading to the progression of prostate tumor. This newly discovered circRNA biomarker may be used for clinical prognosis of prostate cancer as well as for development of novel therapy plans.

Background Right-sided colorectal cancer (RCRC) and left-sided colorectal cancer (LCRC) harbor different genetic alterations associated with immune response. Objective This study aimed to analyze the differences in T cell immune-related RNA expression patterns between RCRC and LCRC. Methods The differentially expressed genes (DEGs) and lncRNAs (DElncRNAs) between LCRC and RCRC were screened from the Cancer Genome Atlas (TCGA) database. A correlation analysis between DEGs or DElncRNAs and differential T cells was also performed to obtain T cell-related genes, followed by miRNA prediction. The mRNA-lncRNA network and the competitive endogenous RNA (ceRNA) network were subsequently constructed, and the expression level of mRNA in the ceRNA network was verified using GSE104645. Results RCRC patients had a poorer prognosis and were older than LCRC patients. In total, 923 DEGs and 328 DElncRNAs were screened between LCRC and RCRC patients. Compared to RCRC patients, LCRC patients showed a decrease in CD8+ T cells. In addition, 26 miRNAs, 8 mRNAs, and 10 lncRNAs were included in the ceRNA network. Finally, the validation analysis revealed that CDHR1 and PRLR were significantly downregulated, while TRIB2 was upregulated in RCRC patients compared to LCRC patients. Conclusion The analysis of T cell immune-related RNA expression might provide new insights into the underlying molecular mechanisms of the differences between LCRC and RCRC.

Papillary thyroid carcinoma (PTC) is the most frequent histological type of differentiated thyroid carcinoma. Long noncoding RNAs (lncRNAs) have been widely reported to play a key role in human malignancies, and PTC is included. This study aimed to find out the functions and mechanism of lncRNA LINC00475 in PTC. LINC00475 was upregulated in PTC cells and was mainly located in the cytoplasm according to reverse-transcription polymerase chain reaction analyses and subcellular fractionation assays. As shown by cell counting kit-8 assays, ethynyl deoxyuridine incorporation assays, wound healing assays, and transwell assays, LINC00475 knockdown suppressed cell viability, proliferation, migration, and invasion. Mechanistically, LINC00475 upregulated the expression of messenger RNA zinc finger CCHC-type containing 12 (ZCCHC12) by binding to miR-376c-3p. ZCCHC12 was a direct target gene of miR-376c-3p in PTC cells. The relationship between miR-376c-3p and LINC00475 (or ZCCHC12) in PTC cells was probed by luciferase reporter assays, RNA pulldown assays, and RNA immunoprecipitation assays. In addition, both mRNA and protein levels of ZCCHC12 were downregulated due to miR-376c-3p overexpression or LINC00475 silencing. ZCCHC12 overexpression partially reversed the suppressive effect of LINC00475 knockdown on malignant behaviors of PTC cells. In conclusion, LINC00475 promotes PTC cell proliferation, migration, and invasion by upregulating ZCCHC12 via the interaction with miR-376c-3p.

Background Parkinson’s disease (PD) is a common neurodegenerative disease in the elderly population. However, there are no reliable diagnostic biomarkers for PD, and the pathogenesis of PD still needs further study. The aim of the current study was to identify potential biomarkers and explore the pathogenesis of PD. Methods We conducted an integrative analysis of messenger RNA (mRNA), microRNA (miRNA), and long noncoding RNA (lncRNA) expression profiles of PD using data from the Gene Expression Omnibus (GEO). The GSE110720, GSE110719 and GSE133347 data sets were selected and analysed. Gene ontology (GO) enrichment and gene set variation analysis (GSVA) were performed for annotation, visualization, and integrated discovery. Protein–protein interaction (PPI) and competing endogenous RNA (ceRNA) networks were constructed, and hub genes were identified. Meanwhile, the immune infiltration analysis of hub genes was analysed. Moreover, receiver operating characteristic (ROC) curves were generated to verify the diagnostic value of the differentially expressed genes (DEGs). Finally, the genes with high area under the curve (AUC) values were verified by human samples. Results We identified 464 DEGs closely related to PD, including 154 mRNAs, 134 miRNAs, and 176 lncRNAs. The GO analyses indicated that changes in PD were mainly enriched in receptor ligand activity and cytokine receptor binding. The KEGG enrichment analysis showed that these DEGs were significantly involved in cytokine-cytokine receptor interactions, signalling pathways regulating the pluripotency of stem cells and Th17 cell differentiation. GSVA suggested that growth factor binding, IL2-stat5 signalling, and IL6-jak-stat3 signalling were crucial in the development of PD. A total of five hub genes (NPBWR2, CXCL10, CXCL5, S1PR5, and GALR1) were selected via the PPI network. A ceRNA network of the CXCL5, CXCL10 and S1PR5 genes was constructed, and target genes of the three genes were screened. The immune infiltration analysis showed that there were significant differences in a variety of immune cells between the hub genes. The expression of DEGs was validated in clinical human samples by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The expression levels of hsa-miR6895–5p, hsa-miR6791–5p, hsa-miR518f-5p, hsa-miR455–3p and TEKT4P2 were decreased, while the levels of TPTE2P6 were increased in human samples. These findings are consistent with the bioinformatics analysis results. Conclusion We found that the immune inflammatory response and immune cell regulation were involved in the pathogenesis of PD. Five hub genes involved in the immune infiltration biological processes of PD based on bioinformatics. We verified the DEGs with significant differences by qRT-PCR. These findings might provide new insight into the pathogenesis of PD and the development of diagnostic and therapeutic strategies for PD.

Circular RNAs (circRNAs) are covalently closed RNA molecules that play important regulatory roles in various tumors. Prostate cancer (PCa) is one of the most common malignant tumors in the world, with high morbidity and mortality. In recent years, more and more circRNAs have been found to be abnormally expressed and involved in the occurrence and development of PCa, including cell proliferation, apoptosis, invasion, migration, metastasis, chemotherapy resistance, and radiotherapy resistance. Most of the circRNAs regulate biological behaviors of cancer through a competitive endogenous RNA (ceRNA) regulatory mechanism, and some can exert their functions by binding to proteins. circRNAs are also associated with many clinicopathological features of PCa, including tumor grade, lymph node metastasis, and distant metastasis. In addition, circRNAs are potential diagnostic and prognostic biomarkers for PCa. Considering their critical regulatory roles in the progression of PCa, circRNAs would be the potential therapeutic targets. In this paper, the current research status of circRNAs in PCa is briefly reviewed., Graphical abstract, This paper reviews the role and clinical significance of circRNA in the occurrence and development of prostate cancer, so as to provide a comprehensive understanding of the relationship between circRNA and prostate cancer.

Long non-coding RNAs (lncRNAs) are critical regulators of hepatocellular carcinoma (HCC) carcinogenesis and development. We aimed to identify the function of the lncRNA ASMTL-AS1 during HCC malignancy. The expression of ASMTL-AS1, miR-1343-3p, and LAMC1 (laminin subunit gamma 1) was assessed in HCC tissues and cells. Cell Counting Kit-8 (CCK8) and Transwell migration assays were performed to determine the effect of ASMTL-AS1 on HCC cell proliferation and migration. Cell apoptosis was identified by detecting Bax and Bcl-2 protein expression using Western blotting, and a xenograft assay was performed to investigate tumor growth in vivo. The interplay between miR-1343-3p and ASMTL-AS1 or LAMC1 was verified through luciferase reporter and RNA immunoprecipitation assays. ASMTL-AS1 and LAMC1 were highly expressed in HCC tissues and cells, whereas miR-1343-3p showed low expression. Clinically, miR-1343-3p expression in HCC tissues showed a negative correlation with ASMTL-AS1 or LAMC1 expression. Functional assays demonstrated that ASMTL-AS1 silencing suppressed HCC cell proliferation and migration and increased cell apoptosis. More interestingly, ASMTL-AS1 sponged miR-1343-3p and miR-1343-3p to target the 3ʹ-UTR of LAMC1, thereby interfering with the malignant behavior of HCC cells. In conclusion, ASMTL-AS1 acts as a carcinogen in HCC through competing endogenous RNA (ceRNA) activity in the miR-1343-3p/LAMC1 axis. Our findings demonstrate that regulating ASMTL-AS1/miR-1343-3p/LAMC1-mediated HCC cell malignancy might be an effective method to interfere with HCC progression.

Long noncoding RNAs (lncRNAs) are emerging as critical regulators of gene expression and play fundamental roles in immune regulation. Growing evidence suggests that immune-related genes and lncRNAs can serve as markers to predict the prognosis of patients with cancers, including hepatocellular carcinoma (HCC). This study aimed to contract an immune-related lncRNA (IR-lncRNA) signature for prospective assessment to predict early recurrence of HCC. A total of 319 HCC samples under radical resection were randomly divided into a training cohort (161 samples) and a testing cohort (158 samples). In the training dataset, univariate, lasso, and multivariate Cox regression analyses identified a 9-IR-lncRNA signature closely related to disease-free survival. Kaplan-Meier analysis, principal component analysis, gene set enrichment analysis, and nomogram were used to evaluate the risk model. The results were further confirmed in the testing cohort. Furthermore, we constructed a competitive endogenous RNA regulatory network. The results of the present study indicated that this 9-IR-lncRNA signature has important clinical implications for improving predictive outcomes and guiding individualized treatment in HCC patients. These IR-lncRNAs and regulated genes may be potential biomarkers associated with the prognosis of HCC., Graphical abstract, In this paper, we applied multiple bioinformatics methods and constructed a 9-immune-related long noncoding RNA (IR-lncRNA) signature closely related to HCC recurrence. We further constructed an IR-lncRNA-associated competitive endogenous RNA (ceRNA) network based on multiple microRNA (miRNA) target databases. The hub genes in the ceRNA network may act as potential biomarkers and novel therapeutic targets for HCC.

Chenglin Ye,1 Sizhe Zhu,2 Jingping Yuan1 1Department of Pathology, Renmin Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China; 2Department of Clinical Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, Hubei, People’s Republic of ChinaCorrespondence: Jingping Yuan; Sizhe Zhu Email yuanjingping@whu.edu.cn; zhusizhe@hust.edu.cnPurpose: We aimed to construct a competing endogenous RNA (ceRNA) network and explore the potential biomarkers in Crohn’s disease (CD) via bioinformatics analysis. Validation of candidate biomarkers in a 2,4,6-trinitrobenzene sulfonic acid (TNBS) induced experimental colitis model and ceRNA network in an HCT116 cell line was also an aim, along with purposing to reveal the pathogenesis of CD.Methods: GSE102134 and GSE67106 datasets were obtained and used to screen the differentially expressed genes. WCGNA was applied to identify the relative model to construct the ceRNA network. Furthermore, the relationship between candidate gene and immune infiltration was investigated. Then, the expression of potential biomarkers was validated via qRT-PCR in a TNBS induced experimental colitis model. Finally, the ceRNA network was confirmed by RNAi experiments in an HCT116 cell line.Results: The ceRNA network, consisting of four lncRNAs, four miRNAs, and eight mRNAs, was constructed and the ROC analysis showed four mRNAs (PTGS2, LPL, STAT1, and TRIB2) had high diagnostic accuracy (AUC> 0.9). In addition, upregulated PTGS2 was positively correlated with immune cell infiltration, including Natural killer cells, exhausted T-cells, monocytes, and Dendritic cells. The outcome of this TNBS induced experimental colitis model verified that the expression of PTGS2 and mir-429 was consistent with results of previous bioinformatics analysis. Furthermore, the predicted ceRNA network MIR3142HG/mir-429/PTGS2 were validated via RNA interference. Knockout of MIR3142HG decreased the mRNA level of PTGS2, whereas inhibition of mir-429 increased the mRNA level of PTGS2 in the HCT116 cell line.Conclusion: The exploration of the ceRNA network in this work might contribute to understanding the pathogenesis of CD. The constructed MIR3142HG/mir-429/PTGS2 ceRNA network may play a role in CD, and PTGS2 can be a potential immune-related biomarker in CD.Keywords: Crohn’s disease, ceRNA network, bioinformatics analysis, WCGNA, validation, experimental colitis mice model

Nasopharyngeal carcinoma (NPC) is a common tumor in the head and neck and is prevalent in China, especially in the southern regions. Molecular mechanisms have attracted much attention in NPC research. FOXD1 has been reported to be a tumor promoter in various cancers. The present study was designed to explore the function of FOXD1 in NPC cells. Functional analyses, including the trypan blue staining assay, EdU and JC-1 assay, and flow cytometry analysis, revealed that FOXD1 facilitated NPC cell proliferation and inhibited NPC cell apoptosis. Next, by means of “starBase” database and mechanism analyses, such as RIP assay, RNA pull-down assay and luciferase reporter assay, miR-378a-3p was found to target FOXD1 and negatively regulate FOXD1 expression in NPC cells. Moreover, miR-378a-3p plays a suppressive role in NPC cells. LINC00641 was identified as a sponge of miR-378a-3p and positively modulated FOXD1 expression in NPC cells. Finally, a series of rescue assays indicated that LINC00641 accelerated NPC cell proliferation and hindered NPC cell apoptosis through FOXD1 upregulation. In conclusion, the present study demonstrated an innovative ceRNA mechanism of LINC00641/miR-378a-3p/FOXD1 in NPC cells, which might provide new insights into NPC treatment.

Transcriptome expression profiles of laryngeal squamous cell carcinoma (LSCC) are altered, and we aimed to investigate expression and role of hsa_circ_0005033 (circ_0005033), microRNA (miR)-107 and insulin-like growth factor 1 receptor (IGF1R) in LSCC. Real-time PCR, western blotting and immunohistochemistry detected RNA and protein expression levels. Functional assays were performed using MTT assay, EdU assay, apoptosis assay, flow cytometry, Transwell assay, and xenograft tumor model. Direct interaction was predicted by Starbase algorithm and validated by dual-luciferase reporter assay and RNA immunoprecipitation. Expression of circ_0005033 was substantially upregulated in LSCC tissues and cells, and allied with miR-107 downregulation and IGF1R upregulation. Circ_0005033 showed a closed-loop structure and long half-life. Essentially, circ_0005033 and IGF1R were competing endogenous RNAs for miR-107 via target binding. Silencing circ_0005033 facilitated apoptosis rate and lowered cell viability, proliferation, migration and invasion of LSCC cells, as well as delayed xenograft tumor growth. Allied with that, cleaved-caspase 3/8/9 expression was elevated via death receptor-mediated and mitochondrial pathways, and expression of matrix metalloproteinase-2 (MMP2), MMP9, cyclin D1 and proliferating cell nuclear antigen was decreased. Moreover, Cisplatin-induced inhibition of cell viability was exacerbated by inhibiting circ_0005033. These functional effects of circ_0005033 depression were consistent with those of miR-107 overexpression. Furthermore, depleting miR-107 and restoring IGF1R abated the effects of circ_0005033 knockdown and miR-107 overexpression, respectively. Circ_0005033 was oncogenic in LSCC by regulating cell progression and Cisplatin sensitivity at least via miR-107/IGF1R axis.

Long non‐coding RNAs (LncRNAs), which are more than 200 nucleotides in length and with limited protein‐coding potential, play vital roles in the pathogenesis, tumorigenesis, and angiogenesis of cancers. Aberrant expression of lncRNAs has been detected in various carcinomas and may be correlated with oncogenesis by affecting related genes expression. Recently, an increasing number of studies have reported on long intergenic non‐protein coding RNA 460 (LINC00460) in human tumor fields. LINC00460 is upregulated in diverse cancer tissues and cells. The upregulated expression level of LINC00460 is correlated with larger tumor size, tumor node metastasis (TNM) stage, lymph node metastasis, and shorter overall survival. The regulatory mechanism of LINC00460 was complex and diverse. LINC00460 could act as a competitive endogenous RNA (ceRNA), directly bind with proteins or regulate multiple pathways, which affected tumor progression. Moreover, LINC00460 was also identified to increase drug resistance, and therefore, weaken the effectiveness of tumor treatment. It has become increasingly important to investigate the roles of LINC00460 in various cancers by different mechanisms. Therefore, a more comprehensive understanding of LINC00460 is crucial to expound on the cellular function and molecular mechanism of human cancers. In this review, we refer to studies concerning LINC00460 and provide the basis for the evaluation of LINC00460 as a predicted biomarker or potential therapeutic target in malignancies, and also provide ideas for the future research of lncRNAs similar to LINC00460., In recent years, the regulatory role of long noncoding RNAs (lncRNAs) in human tumors has been gradually recognized. In this review, we respectively showed how lncRNA LINC00460 affected progression of human tumors in different types by multiple mechanisms. A large number of previous researches have demonstrated that LINC00460 as an oncogene plays important roles in tumor growth, development, and metastasis. In view of the important role of LINC00460 in tumorigenesis and development as well as its significance as a biomarker, we summarized the specific role and molecular mechanism of LINC00460 in various tumors, convenient for readers integrally learning about the effect of LINC00460 on diverse cancers. We believe this review is valuable for all the researchers who are interested in human cancers and noncoding RNAs.

Bladder cancer (BC) is one of the most common malignant tumors in the urinary system. Our research aimed to explore the function and underlying mechanisms of long noncoding RNA (lncRNA) PSMA3-AS1 in BC. RT-qPCR was utilized to detect the levels of PSMA3-AS1, miR-214-5p, and PD-L1. ChIP assay was employed to confirm the transcription factor of PSMA3-AS1. Luciferase reporter assay was carried out to demonstrate the relationships between miR-214-5p and PSMA3-AS1 or PD-L1. The diagnostic value of PSMA3-AS1 was evaluated by the ROC curve. CCK-8, wound healing, transwell, and flow cytometry assays were applied to analyze cell viability, migration, invasion, and apoptosis. Western blotting was used to confirm the expression of cleaved caspase-3. The present study revealed that BC tissues and cells exhibited an increased expression in PSMA3-AS1. High expression of PSMA3-AS1 was related to poor prognosis in BC patients. Then, the area under the ROC curve for PSMA3-AS1 was up to 0.8954. Moreover, ChIP assay elaborated that YY1 could bind to the PSMA3-AS1 promoter region. Furthermore, it was found that that PSMA3-AS1 knockdown repressed BC cell viability and metastasis, and promoted apoptosis. In addition, miR-214-5p was inversely correlated with PSMA3-AS1 or PD-L1 levels. MiR-214-5p deletion reversed the impacts of PSMA3-AS1 deletion on BC progression, and PD-L1 inhibition also abrogated the influence of miR-214-5p deletion in BC development. In conclusion, YY1-induced PSMA3-AS1 exerted an oncogenic function in BC cells via targeting miR-214-5p and enhancing PD-L1, providing potential biomarkers for BC therapy.

Purpose Dysregulation of long non-coding RNAs (lncRNAs) is being found to have relevance to human cancers, including breast cancer (BC). The aim of this study was to further explore the functional role and molecular mechanisms of small nucleolar RNA host gene 14 (SNHG14) on BC progression. Methods The expression levels of SNHG14, miR-543, and kruppel-like factor 7 (KLF7) mRNA were determined by quantitative real-time PCR. Western blot analysis was used to evaluate KLF7 protein level. Cell proliferation, apoptosis, and migration and invasion abilities were detected by Cell Counting kit-8 assay, flow cytometry, and transwell assay, respectively. The direct interactions between miR-543 and SNHG14 or KLF7 were confirmed using dual-luciferase reporter assays. Results Our data indicated that SNHG14 expression was increased in BC tissues and cells, and SNHG14 knockdown mitigated the proliferation, migration, and invasion and facilitated apoptosis of BC cells. SNHG14 directly interacted with miR-543. MiR-543 mediated the regulatory effects of SNHG14 silencing on BC cell behaviors. Moreover, KLF7 was a direct target of miR-543. Overexpressed miR-543-mediated anti-proliferation, anti-migration, anti-invasion, and pro-apoptosis effects were mediated by KLF7. Furthermore, SNHG14 modulated KFL7 expression through acting as a competing endogenous RNA (ceRNA) of miR-543 in BC cells. Conclusion Our study suggested that SNHG14 knockdown hindered BC progression in vitro at least partly through acting as a ceRNA of miR-543 and modulating KLF7 expression, providing evidence for SNHG14 as a potential target for BC therapy.

BACKGROUND AND PURPOSE This study was undertaken to screen the circular RNAs (circRNAs) influencing matrix metalloproteinase 9 (MMP9) through the competing endogenous RNA (ceRNA) network and evaluate the prognostic value of these circRNAs for acute ischemic stroke. METHODS A total of 220 ischemic stroke patients and 62 healthy subjects were included in this study. RNA was isolated from blood collected in PAXgene tubes. Illumina sequencing, quantitative real-time polymerase chain reaction (qRT-PCR) validation, and luciferase reporter assay were explored to construct and verify the existence of a circRNA-microRNA (miRNA)-matrix metalloproteinase-9 (MMP9) network. The 215 ischemic stroke patients were recruited in a prognostic cohort. They were prospectively followed up for 3 months after stroke onset, and a poor functional outcome was defined as a major disability or death. RESULTS After Illumina sequencing, six circRNAs were predicted to bind miRNAs and then regulate MMP9 messenger RNA (mRNA). qRT-PCR showed that only circSKA3 was significantly increased in ischemic stroke patients compared to healthy controls and positively associated with MMP9 mRNA expression. Luciferase reporter assay further verified a direct interaction between circSKA3, MMP9, and hsa-miR-6796-5p. Patients in the top tertile of circSKA3 had a 2.672-fold (p

Background. Abdominal aortic aneurysm (AAA) is a progressive cardiovascular disease, which is a permanent and localized dilatation of the abdominal aorta with potentially fatal consequence of aortic rupture. Dysregulation of circRNAs is correlated with the development of various pathological events in cardiovascular diseases. However, the function of circRNAs in abdominal aortic aneurysm (AAA) is unknown and remains to be explored. This study is aimed at determining the regulatory mechanisms of circRNAs in AAAs. This study was aimed at exploring the underlying molecular mechanisms of abdominal aortic aneurysms based on the competing endogenous RNA (ceRNA) regulatory hypothesis of circRNA, miRNA, and mRNA. Methods. The expression profiles of circRNAs (GSE144431), miRNAs (GSE62179), and mRNAs (GSE7084, GSE57691, and GSE47472) in human tissue sample from the aneurysm group and normal group were obtained from the Gene Expression Omnibus database, respectively. The circRNA-miRNA-mRNA network was constructed by using Cytoscape 3.7.2 software; then, the protein-protein interaction (PPI) network was constructed by using the STRING database, and the hub genes were identified by using the cytoHubba plug-in. The circRNA-miRNA-hub gene regulatory subnetwork was formed to understand the regulatory axis of hub genes in AAAs. Results. The present study identified 40 differentially expressed circRNAs (DECs) in the GSE144431, 90 differentially expressed miRNAs (DEmiRs) in the GSE62179, and 168 differentially expressed mRNAs (DEGs) with the same direction regulation (130 downregulated and 38 upregulated) in the GSE7084, GSE57691, and GSE47472 datasets identified regarding AAAs. The miRNA response elements (MREs) of three DECs were then predicted. Four overlapping miRNAs were obtained by intersecting the predicted miRNA and DEmiRs. Then, 17 overlapping mRNAs were obtained by intersecting the predicted target mRNAs of 4 miRNAs with 168 DEGs. Furthermore, the circRNA-miRNA-mRNA network was constructed through 3 circRNAs, 4 miRNAs, and 17 mRNAs, and three hub genes (SOD2, CCR7, and PGRMC1) were identified. Simultaneously, functional enrichment and pathway analysis were performed within genes in the circRNA-miRNA-mRNA network. Three of them (SOD2, CCR7, and PGRMC1) were suggested to be crucial based on functional enrichment, protein-protein interaction, and ceRNA network analysis. Furthermore, the expression of SOD2 and CCR7 may be regulated by hsa_circ_0011449/hsa_circ_0081968/hsa-let-7f-5p; the expression of PGRMC1 may be regulated by hsa_circ_0011449/hsa_circ_0081968-hsa-let-7f-5p/hsa-let-7e-5p. Conclusion. In conclusion, the ceRNA interaction axis we identified may be an important target for the treatment of abdominal aortic aneurysms. This study provided further understanding of the potential pathogenesis from the perspective of the circRNA-related competitive endogenous RNA network in AAAs.

Background Recurrent spontaneous abortion (RSA) is one of the common complication of pregnancy, bringing heavy burden to the patients and their families. The study aimed to explore the lncRNA-miRNA-mRNA network associated with recurrent spontaneous abortion. Methods By transcriptome sequencing, we detected differences in lncRNA, miRNA and mRNA expression in villus tissue samples collected from 3 patients with RSA and 3 normal abortion patients. Differentially expressed lncRNAs, miRNAs and genes (DELs, DEMs and DEGs, respectively) were identified, and Geno Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to determine the functions of DELs and DEGs, which were analysed by Fisher’s test. We also observed the regulatory relationships between miRNA-mRNA and lncRNA-miRNA by Cytoscape 3.6.1. Results The results showed that 1008 DELs (523 upregulated and 485 downregulated), 475 DEGs (201 upregulated and 274 downregulated) and 37 DEMs (15 upregulated and 22 downregulated) were identified. And we also constructed a novel lncRNA-related ceRNA network containing 31 lncRNAs, 1 miRNA (hsa-miR-210-5p) and 3 genes (NTNG2, GRIA1 and AQP1). Conclusions lncRNA-related ceRNA network containing 31 lncRNAs, 1 miRNA (hsa-miR-210-5p) and 3 mRNAs (NTNG2, GRIA1 and AQP1) was constructed. The results may provide a basic theory for elucidating the mechanism underlying RSA.

Most patients with hepatocellular carcinoma (HCC) are in the middle or advanced stage at the time of diagnosis, and the therapeutic effect is limited. Therefore, this study aimed to verify whether deoxythymidylate kinase (DTYMK) increased in HCC and was an effective therapeutic target in HCC. The findings revealed that the DTYMK level significantly increased and correlated with poor prognosis in HCC. However, nothing else is known, except that DTYMK could catalyze the phosphorylation of deoxythymidine monophosphate (dTMP) to form deoxythymidine diphosphate (dTDP). A number of experiments were performed to study the function of DTYMK in vitro and in vivo to resolve this knowledge gap. The knockdown of DTYMK was found to significantly inhibit the growth of HCC and increase the sensitivity to oxaliplatin, which is commonly used in HCC treatment. Moreover, DTYMK was found to competitively combine with miR-378a-3p to maintain the expression of MAPK activated protein kinase 2 (MAPKAPK2) and thus activate the phospho-heat shock protein 27 (phospho-HSP27)/nuclear factor NF-kappaB (NF-κB) axis, which mediated the drug resistance, proliferation of tumor cells, and infiltration of tumor-associated macrophages by inducing the expression of C-C motif chemokine ligand 5 (CCL5). Thus, this study demonstrated a new mechanism and provided a new insight into the role of mRNA in not only encoding proteins to regulate the process of life but also regulating the expression of other genes and tumor microenvironment through the competing endogenous RNA (ceRNA) mechanism.

Mengxiong Li,1,* Zhi Zeng,2,* Aiqing Zhang,3 Qingjian Ye,4 Shujun Su,4 Tingting Xia5 1Department of Obstetrics and Gynecology, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, 518107, People’s Republic of China; 2The Department of Reproductive Medicine Center, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510000, People’s Republic of China; 3Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, 510630, People’s Republic of China; 4Department of Gynecology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, 510630, People’s Republic of China; 5Center for Reproductive Medicine, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, 510630, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tingting Xia Tel +86-020-85256032Email xiatting@mail.sysu.edu.cnObjective: Dysfunction of cumulus granulosa cells has been suggested as a contributor to abnormal folliculogenesis and the development of polycystic ovary syndrome (PCOS), but the underlying molecular mechanisms remain unclear. Recent studies indicate that circular RNAs (circRNAs) exert important roles for diseases. We aimed to screen crucial circRNAs of PCOS patients and predict their functions.Methods: The high-throughput datasets of circRNAs (GSE145296), microRNAs (miRNAs; GSE72274) and messenger RNAs (mRNAs; GSE155489) in cumulus cells of PCOS patients and controls were collected from the Gene Expression Omnibus database. Differentially expressed circRNAs (DECs), miRNAs (DEMs) and protein-coding genes (DEGs) were identified by the limma method. The weighted correlation network analysis (WGCNA) was conducted using the DECs to mine PCOS-associated modules. Hub DECs in modules were defined as both of |gene significance| and |module membership| > 0.8. The downstream effectors of hub DECs were predicted by constructing DEC-DEM-DEG ceRNA and DEC-RNA binding protein (RBP) networks. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to explore the functions of circRNAs.Results: A total of 3614 DECs, 3544 DEGs and 1469 DEMs were identified between PCOS and controls. WGCNA analysis yielded five PCOS-related modules, of which 190 DECs were hub circRNAs. Seventeen hub DECs, nine DEMs, and 315 DEGs were identified to construct the ceRNA network, while 56 hub DECs and two DEGs (MBNL2, RBPMS) constituted the circRNA-RBP network. Five hub DECs (hsa_circ_0063309, hsa_circ_0054275, hsa_circ_0056196, hsa_circ_0018108 and hsa_circ_0070987) were overlapped between ceRNA and DEC-MBNL2 regulatory networks and thus they may be pivotal for PCOS. Furthermore, hsa_circ_0099109 could interact with the RBP gene RBPMS. Function analyses showed these circRNAs were inflammation-, apoptosis- or steroidogenesis-related.Conclusion: Aberrant expression of six circRNAs that function as RBP regulators or miRNA sponges may be possible mechanisms underlying the pathogenesis of PCOS by affecting apoptosis and steroidogenesis in cumulus cells.Keywords: circular RNAs, competitive endogenous RNAs, polycystic ovary syndrome, RNA-binding proteins, weighted gene co-expression network analysis

Leydig cells (LCs) apoptosis is responsible for the deficiency of serum testosterone in Late-onset hypogonadism (LOH), while its specific mechanism is still unknown. This study focuses on the role of long noncoding RNA (lncRNA) MIR22HG in LC apoptosis and aims to elaborate its regulatory mechanism. MIR22HG was up-regulated in the testicular tissues of mice with LOH and H2O2-treated TM3 cells (mouse Leydig cell line). Interference of MIR22HG ameliorated cell apoptosis and upregulated miR-125a-5p expression in H2O2-treated TM3 cells. Then, the interaction between MIR22HG and miR-125a-5p was confirmed with RIP and RNA pull-down assay. Further study showed that miR-125a-5p downregulated N-Myc downstream-regulated gene 2 (NDRG2) expression by targeting its 3'-UTR of mRNA. What's more, MIR22HG overexpression aggravated cell apoptosis and reduced testosterone production in TM3 cells via miR-125a-5p/NDRG2 pathway. MIR22HG knockdown elevated testosterone levels in LOH mice. In conclusion, MIR22HG up-regulated NDRG2 expression through targeting miR-125a-5p, thus promoting LC apoptosis in LOH.

Background We aim to discover some prognostic factors, provide a basis for discovering molecular markers, and provide a basis for molecular features of early lung adenocarcinoma (LUAD) to predict patient prognosis. Methods Sequence data of LUAD were downloaded from The Cancer Genome Atlas (TCGA) database to screen out differentially expressed lncRNAs, miRNAs, and mRNAs (DERs). DERs were identified using R software’s limma package. The competitive endogenous RNA (ceRNA) network was constructed based on these RNAs. Univariate and multivariate Cox regression analysis on the RNAs in the ceRNA screened out independent prognostic-related RNAs to construct a prognostic risk score (PS) model. Combined with clinical data, we can calculate the survival rate of patients with early LUAD. Results There were 2,701 differentially expressed mRNAs (DEmRNAs), 47 differentially expressed lncRNAs (DElncRNAs), and 161 differentially expressed miRNAs (DEmiRNAs) identified in early LUAD. Based on these RNAs, 32 lncRNAs, 87 miRNAs, and 174 mRNAs participated in the ceRNA network. Twelve independently prognostic-related RNAs form an optimized combination. We developed a PS model based on these RNAs. Age, tumor recurrence and PS model status were independent survival prognostic clinical factors. Nomogram was established to predict the 3-year and 5-year survival rates. Conclusions We successfully constructed a ceRNA regulatory network based on the DERs in early LUAD. It can help us clarify the molecular mechanism of early LUAD. Simultaneously, the prognostic-related RNAs in early LUAD were also screened out. This network could provide new bases for diagnoses and prognoses of patients with LUAD.

While long noncoding RNAs (lncRNAs) have been reported to play an important role in human cancer types, they remain poorly understood in papillary thyroid carcinoma (PTC). The aim of this study was to use genome-wide expression profiling to identify lncRNAs acting as competing endogenous RNAs (ceRNAs) in PTC. We constructed a ceRNA network based on our lncRNA microarray data and validated the correlation between myocardial infarction-associated transcript lncRNA (MIAT), miRNA-150-5p, and EZH2 in vitro and in vivo. We found 15 lncRNAs, 28 miRNAs, and hundreds of mRNAs involved in this ceRNA network. Splendid positive correlations were found between the MIAT and EZH2 expression in types of cancer in TCGA data. Besides, significant differences in MIAT/EZH2 expression were found among various clinicopathological features. Gain- and loss-of-function experiments revealed that MIAT inhibited cell proliferation and migration in vitro. Moreover, EZH2 was identified as a direct downstream target of miR-150-5p in PTC cells. Restoration of EZH2 expression partially abolished the biological effects of miR-150-5p. Furthermore, overexpression of MIAT was inversely correlated with miR-150-5p expression. Knockdown of MIAT produced significant behavioral alter maybe partly due to the function of the MIAT-150-5p-EZH2 network. Our findings suggest MIAT may inhibit EZH2 expression and promote PTC cell invasion via the miR-150/EZH2 pathway. Therefore, MIAT may serve as a valuable prognostic biomarker and therapeutic target for PTC.

Emerging evidence has demonstrated that circular RNAs (circRNAs) take part in the initiation and development of pancreatic ductal adenocarcinoma (PDA), a deadly neoplasm with an extremely low 5-year survival rate. Reprogrammed glucose metabolism is a key feature of tumour development, including PDA. In this research, we evaluated the role of circRNAs in reprogrammed glucose metabolism in PDA. RNA sequencing under various glucose incubation circumstances was performed. A new circMYOF was identified. Sanger sequencing and RNase R treatment confirmed its circular RNA characteristics. Real-time PCR indicated that it was highly expressed in PDA clinical specimens and cell lines. Gain-of- and loss-of-function assays showed that circMYOF induced progression in PDA. Mechanistically, RNA pull-down and luciferase reporter experiments elucidated that circMYOF, as a competing endogenous RNA for miR-4739, facilitated glycolysis via the VEGFA/PI3K/AKT pathway. Taken together, our findings indicate that circMYOF may work as a desirable biomarker and therapeutic target for PDA patients.

Background: Evidence from previous investigations points to a rising trend in the incidence of colorectal cancer (CRC) worldwide. The mortality resulting from this cancer is high. Unlike nonsmall cell lung cancer for which LINC01123 has been investigated, there are few reports on how this long noncoding RNA (lncRNA) regulates CRC. Materials and Methods: The authors evaluated the expression of LINC01123 in CRC tissues by quantitative real-time polymerase chain reaction. Its impact on cancer cell behavior was analyzed with cell counting kit-8 (CCK-8), colony formation, and Transwell invasion assays. To establish the mechanisms of LINC01123 in CRC they carried out RIP and luciferase reporter assays. Results: The results show that LINC01123 expression is abnormally elevated in CRC tissues and cell lines. High LINC01123 expression closely correlates with poor prognosis, advanced TNM stage, and lymph-node metastasis. The authors also show that knockdown of LINC01123 inhibits proliferation and invasion in CRC cells. In mechanism, it is revealed that LINC01123 may function as competitive endogenous RNA (ceRNA) against miR-625-5p to promote LIM and SH3 protein 1 (LASP1) expression. Conclusions: The data indicate that high LINC01123 exerts its oncogenic roles by regulating the miR-625-5p/LASP1 axis in CRC progression.

Xing Liu,1 Guoqiang Zhong,2 Wenbin Li,1 Yiqian Zeng,3 Mingxing Wu1 1Department of Cardiology, Xiangtan Central Hospital, Xiangtan, Hunan, People’s Republic of China; 2Department of Cardiology, Guangxi Cardiovascular Institute, The First Affiliated Hospital of Guangxi Medical University, Guangxi, People’s Republic of China; 3Department of Critical Care Medicine, Zhuzhou Central Hospital, Zhuzhou, Hunan, People’s Republic of ChinaCorrespondence: Yiqian ZengDepartment of Critical Care Medicine, Zhuzhou Central Hospital, Zhuzhou, Hunan, People’s Republic of ChinaEmail zengyiqian@stu.gxmu.edu.cnMingxing WuDepartment of Cardiology, Xiangtan Central Hospital, Xiangtan, Hunan, People’s Republic of China Email wmx917121@126.comBackground: At present, the mechanisms behind atrial fibrillation (AF) pathogenesis are still unclear. We construct a ceRNA immunoregulatory network to further understand the mechanism of AF.Methods: Four AF mRNA datasets from the Gene Expression Omnibus (GEO) database were integrated by SVA method. AF-related immune genes (AF-IRGs) were selected via combining ImmPort database with the genes in the module most associated with AF obtained by a weighted gene coexpression network analysis (WGCNA). Then, circRNA and miRNA expressions from the GEO database were extracted and mapped with related databases. Next, an immune-related circRNA-miRNA-mRNA ceRNA network was constructed and hub genes were filtered from a protein–protein interaction (PPI) network, and the differentially expressed (DE) hub genes in AF were further screened. Additionally, immune infiltration was investigated in AF by using CIBERSORT. Subsequently, the relationships between DE hub genes and AF-related infiltrating immune cells were performed by using Pearson correlation coefficients. Ulteriorly, the immune-cells-related ceRNA subnetwork in AF was built.Results: A total of 95 AF-IRGs were detected, and an immune-related ceRNA network in AF was constructed with 12 circRNAs, 7 miRNAs and 50 mRNAs. The immune infiltration analysis indicated that a higher level of neutrophils, as well as a lower level of T cells regulatory (Tregs) and NK cells activated in AF. Four DE hub genes (CXCL12, IL7R, TNFSF13B, CD8A) were associated with Tregs or NK cells activated immune cells (P < 0.05). Tregs or NK cells activated immune cells-related ceRNA subnetwork including 5 circRNAs (has_circ_0001190, has_circ_0006725, has_circ_0079284, has_circ_0005299, and has_circ_0002103), 4 miRNAs (has-miR-198, has-miR-623, has-miR-1246, and has-miR-339-3p) and 4 DE hub genes was eventually constructed in AF.Conclusion: Our results provide new insights into the molecular mechanisms governing AF progression from the perspective of immune-related ceRNA network.Keywords: atrial fibrillation, competitive endogenous RNA, immune infiltration

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide due to its high degree of malignancy, high incidence, and low survival rate. However, the underlying mechanisms of hepatocarcinogenesis remain unclear. Long non coding RNA (lncRNA) has been shown as a novel type of RNA. lncRNA by acting as ceRNA can participate in various biological processes of HCC cells, such as tumor cell proliferation, migration, invasion, apoptosis and drug resistance by regulating downstream target gene expression and cancer-related signaling pathways. Meanwhile, lncRNA can predict the efficacy of treatment strategies for HCC and serve as a potential target for the diagnosis and treatment of HCC. Therefore, lncRNA serving as ceRNA may become a vital candidate biomarker for clinical diagnosis and treatment. In this review, the epidemiology of HCC, including morbidity, mortality, regional distribution, risk factors, and current treatment advances, was briefly discussed, and some biological functions of lncRNA in HCC were summarized with emphasis on the molecular mechanism and clinical application of lncRNA-mediated ceRNA regulatory network in HCC. This paper can contribute to the better understanding of the mechanism of the influence of lncRNA-mediated ceRNA networks (ceRNETs) on HCC and provide directions and strategies for future studies.

Long noncoding RNAs (lncRNAs) have emerged as important regulators of osteoarthritis (OA), but the biological roles and clinical significance of most lncRNAs in OA are not fully understood. Microarray analysis was performed to identify differentially expressed lncRNAs, mRNAs, and miRNAs between normal and osteoarthritic cartilage. We found that AC008440.5 (abbreviated AC008), as well as AQP1 and ANKH, were highly expressed in osteoarthritic cartilage, whereas miR-328-3p was expressed at a low level in osteoarthritic cartilage. Functional assays showed that ectopic expression of AC008, AQP1, and ANKH significantly decreased chondrocyte viability and promoted chondrocyte apoptosis and extracellular matrix (ECM) degradation, whereas knockdown of AC008, AQP1, and ANKH resulted in the opposite effects. Moreover, miR-328-3p overexpression increased chondrocyte viability and attenuated chondrocyte apoptosis and ECM degradation, whereas inhibition of miR-328-3p resulted in the opposite effects. Bioinformatics analysis, RNA immunoprecipitation (RIP), and luciferase assays revealed that AC008 functioned as a competing endogenous RNA (ceRNA) to regulate miR-328-3p, which specifically targeted the AQP1 and ANKH genes. In addition, miR-328-3p significantly ameliorated MIA-induced OA, whereas AC008 accelerated OA progression in vivo. Furthermore, fat mass and obesity-associated (FTO)-mediated N6-methyladenosine demethylation downregulated AC008 transcription, while lower FTO expression led to upregulation of AC008 transcription in OA. In conclusion, our data reveal that AC008 plays a critical role in OA pathogenesis via the miR-328-3p‒AQP1/ANKH pathway, suggesting that AC008 may be a potential therapeutic target for OA.