LncRNA ZFHX4-AS1 as a novel biomarker in adrenocortical carcinoma.

Background: Adrenocortical carcinoma (ACC) is a rare and highly aggressive malignant tumor. Currently, there is a lack of reliable prognostic markers in clinical practice. Extensive research has shown that long non-coding RNA (lncRNA) are critical factors in the initiation and progression of cancer, closely associated with early diagnosis and prognosis. Previous studies have identified that ZFHX4 antisense RNA 1 (ZFHX4-AS1) is aberrantly expressed in various cancers and is associated with poor outcomes. This study investigates whether ZFHX4-AS1 affects the prognosis of ACC patients and, if so, the potential mechanisms involved. Methods: In this study, utilizing four multi-center cohorts from The Cancer Genome Atlas (TCGA) program and Gene Expression Omnibus (GEO), we validated the prognostic capability of ZFHX4-AS1 in ACC patients through Kaplan-Meier survival analysis, cox regression models, and nomograms. Then, we explored the biological functions of ZFHX4-AS1 using gene set enrichment analysis (GSEA), competing endogenous RNA (ceRNA) networks, and analyses of somatic mutations and copy number variation (CNV). Finally, in vitro experiments were conducted to further validate the impact of ZFHX4-AS1 on proliferation and migration capabilities of ACC cell lines. Results: Survival analysis indicated that patients in the high ZFHX4-AS1 expression group of ACC had worse prognosis. Cox regression analyses suggested that ZFHX4-AS1 levels were independent risk factors for prognosis. Subsequently, we constructed nomograms based on clinical features and ZFHX4-AS1 levels, demonstrating good predictive performance under the time-dependent receiver operating characteristic (ROC) curve. Analysis based on somatic mutations and CNV revealed that CTNNB1 and 9p21.3-Del drove the expression of ZFHX4-AS1. Cell Counting Kit-8 (CCK-8), colony formation, and Transwell assays confirmed that knockdown of ZFHX4-AS1 inhibited proliferation and migration of ACC cells. Conclusions: This study demonstrates that ZFHX4-AS1 has a reliable predictive value for the prognosis of ACC patients and is a promising biomarker.

In-depth transcriptome profiling of Cherry Valley duck lungs exposed to chronic heat stress.

Amidst rising global temperatures, chronic heat stress (CHS) is increasingly problematic for the poultry industry. While mammalian CHS responses are well-studied, avian-specific research is lacking. This study uses in-depth transcriptome sequencing to evaluate the pulmonary response of Cherry Valley ducks to CHS at ambient temperatures of 20°C and a heat-stressed 29°C. We detailed the CHS-induced gene expression changes, encompassing mRNAs, lncRNAs, and miRNAs. Through protein-protein interaction network analysis, we identified central genes involved in the heat stress response-TLR7, IGF1, MAP3K1, CIITA, LCP2, PRKCB, and PLCB2. Subsequent functional enrichment analysis of the differentially expressed genes and RNA targets revealed significant engagement in immune responses and regulatory processes. KEGG pathway analysis underscored crucial immune pathways, specifically those related to intestinal IgA production and Toll-like receptor signaling, as well as Salmonella infection and calcium signaling pathways. Importantly, we determined six miRNAs-miR-146, miR-217, miR-29a-3p, miR-10926, miR-146b-5p, and miR-17-1-3p-as potential key regulators within the ceRNA network. These findings enhance our comprehension of the physiological adaptation of ducks to CHS and may provide a foundation for developing strategies to improve duck production under thermal stress.

miR-2467-3p/ABLIM1 Axis Mediates the Formation and Progression of Deep Vein Thrombosis by Regulating Inflammation and Oxidative Stress.

Deep vein thrombosis (DVT) is a common postoperative complication of orthopaedic surgery with a complex pathogenesis mechanism. The effect of the miR-2467-3p/acting-binding LIM protein 1 (ABLIM1) axis on thrombus formation and human vascular endothelial cells (HUVECs) progression was evaluated aiming to identify a novel potential biomarker of DVT. DVT rat models were established by inferior vena cava stenosis. The expression of the miR-2467-3p/ABLIM1 axis was analyzed by PCR. HUVECs were induced with oxidative low-density lipoprotein (ox-LDL). Cell growth and motility were assessed by cell counting kit 8 (CCK8) and Transwell assay. The inflammation and oxidative stress were estimated by proinflammatory cytokines and generation of MDA and reactive oxygen species (ROS). ABLIM1 was downregulated in DVT rats. Overexpressing ABLIM1 could suppress the formation of thrombosis and alleviate inflammation and oxidative stress. In HUVECs, ox-LDL induced significantly increased miR-2467-3p and decreased ABLIM1, and miR-2467-3p could negatively regulate ABLIM1. The knockdown of miR-2467-3p could alleviate the inhibited cell growth and motility by ox-LDL, and the inflammation and oxidative stress were also attenuated. While silencing could reverse the effect of miR-2467-3p on ox-LDL-induced HUVECs. The miR-2467-3p/ABLIM1 axis regulates the occurrence and development of DVT through modulating HUVECs inflammation and oxidative stress.

The role of lncRNAs related ceRNA regulatory network in multiple hippocampal pathological processes during the development of perioperative neurocognitive disorders.

Background: Perioperative neurocognitive disorders (PND) refer to neurocognitive abnormalities during perioperative period, which are a great challenge for elderly patients and associated with increased morbidity and mortality. Our studies showed that long non-coding RNAs (lncRNAs) regulate mitochondrial function and aging-related pathologies in the aged hippocampus after anesthesia, and lncRNAs are associated with multiple neurodegenerations. However, the regulatory role of lncRNAs in PND-related pathological processes remains unclear. Methods: A total of 18-month mice were assigned to control and surgery (PND) groups, mice in PND group received sevoflurane anesthesia and laparotomy. Cognitive function was assessed with fear conditioning test. Hippocampal RNAs were isolated for sequencing, lncRNA and microRNA libraries were constructed, mRNAs were identified, Gene Ontology (GO) analysis were performed, and lncRNA-microRNA-mRNA networks were established. qPCR was performed for gene expression verification. Results: A total of 312 differentially expressed (DE) lncRNAs, 340 DE-Transcripts of Uncertain Coding Potential (TUCPs), and 2,003 DEmRNAs were identified in the hippocampus between groups. The lncRNA-microRNA-mRNA competing endogenous RNA (ceRNA) network was constructed with 29 DElncRNAs, 90 microRNAs, 493 DEmRNAs, 148 lncRNA-microRNA interaction pairs, 794 microRNA-mRNA interaction pairs, and 110 lncRNA-mRNA co-expression pairs. 795 GO terms were obtained. Based on the frequencies of involved pathological processes, BP terms were divided into eight categories: neurological system alternation, neuronal development, metabolism alternation, immunity and neuroinflammation, apoptosis and autophagy, cellular communication, molecular modification, and behavior changes. LncRNA-microRNA-mRNA ceRNA networks in these pathological categories were constructed, and involved pathways and targeted genes were revealed. The top relevant lncRNAs in these ceRNA networks included RP23-65G6.4, RP24-396L14.1, RP23-251I16.2, XLOC_113622, RP24-496E14.1, etc., and the top relevant mRNAs in these ceRNA networks included Dlg4 (synaptic function), Avp (lipophagy), Islr2 (synaptic function), Hcrt (regulation of awake behavior), Tnc (neurotransmitter uptake). Conclusion: In summary, we have constructed the lncRNA-associated ceRNA network during PND development in mice, explored the role of lncRNAs in multiple pathological processes in the mouse hippocampus, and provided insights into the potential mechanisms and therapeutic gene targets for PND.

Identification and Characterization of miRNAs and lncRNAs Associated with Salinity Stress in Rice Panicles.

Salinity is a common abiotic stress that limits crop productivity. Although there is a wealth of evidence suggesting that miRNA and lncRNA play important roles in the response to salinity in rice seedlings and reproductive stages, the mechanism by which competing endogenous RNAs (ceRNAs) influence salt tolerance and yield in rice has been rarely reported. In this study, we conducted full whole-transcriptome sequencing of rice panicles during the reproductive period to clarify the role of ceRNAs in the salt stress response and yield. A total of 214 lncRNAs, 79 miRNAs, and 584 mRNAs were identified as differentially expressed RNAs under salt stress. Functional analysis indicates that they play important roles in GO terms such as response to stress, biosynthesis processes, abiotic stimuli, endogenous stimulus, and response to stimulus, as well as in KEGG pathways such as secondary metabolite biosynthesis, carotenoid biosynthesis, metabolic pathways, and phenylpropanoid biosynthesis. A ceRNA network comprising 95 lncRNA-miRNA-mRNA triplets was constructed. Two lncRNAs, MSTRG.51634.2 and MSTRG.48576.1, were predicted to bind to osa-miR172d-5p to regulate the expression of OsMYB2 and OsMADS63, which have been reported to affect salt tolerance and yield, respectively. Three lncRNAs, MSTRG.30876.1, MSTRG.44567.1, and MSTRG.49308.1, may bind to osa-miR5487 to further regulate the expression of a stress protein (LOC_Os07g48460) and an aquaporin protein (LOC_Os02g51110) to regulate the salt stress response. This study is helpful for understanding the underlying molecular mechanisms of ceRNA that drive the response of rice to salt stress and provide new genetic resources for salt-resistant rice breeding.

hsa_circ_0088196 Predicts Adverse Pregnancy Outcomes in Preeclampsia Patients and Contributes to Endothelial Cell Injury Via Modulating the miR-145-5p/FLT1 Axis.

Preeclampsia (PE) is a specific hypertension-related disease in pregnancies, causing adverse pregnancy outcomes. Endothelial cell dysfunction is a major etiology of PE, of which the regulation could affect disease progression. This study focused on hsa_circ_0088196, evaluating its clinical significance in PE and its effect on endothelial cell injury, aiming to identify a novel biomarker for PE and complete its regulating mechanism in disease development. The study enrolled 165 normal pregnancies and 165 pregnancies with gestational hypertension. The significance of hsa_circ_0088196 in discriminating gestational hypertension, predicting PE, and predicting adverse pregnancy outcomes was evaluated based on its serum expression. The effect and mechanism of hsa_circ_0088196 in HUVEC injury were assessed by CCK8, Transwell, ELISA, and western blotting. Significant downregulation of hsa_circ_0088196 could distinguish gestational hypertension pregnancies and predict the risk of PE. Gestational hypertension pregnancies developed PE showed a lower serum hsa_circ_0088196 level, which also discriminated PE patients, predicted severe conditions and adverse pregnancy outcomes. Overexpressing hsa_circ_0088196 alleviated the enhanced proliferation, migration, inflammation, and angiogenesis by hypoxia/reoxygenation (H/R), which was reversed by miR-145-5p. Silencing miR-145-5p showed similar effects on H/R-induced endothelial cell injury, which was reversed by FLT1. Moreover, FLT1 was positively regulated by hsa_circ_0088196, indicating its involvement in the regulation of HUVEC injury by hsa_circ_0088196. Reduced serum hsa_circ_0088196 served as a biomarker for the diagnosis of gestational hypertension, risk evaluation of PE, and the prediction of adverse pregnancy outcomes. hsa_circ_0088196 suppressed endothelial cell injury induced by H/R through modulating the miR-145-5p/FLT1 axis.

microRNA-125b-5p alleviated CCI-induced neuropathic pain and modulated neuroinflammation via targeting SOX11.

BACKGROUND: Increasing evidence demonstrated the involvement of microRNAs (miRNAs) in the onset and development of neuropathic pain (NP). Exploring the molecular mechanism underlying NP and identifying key molecules could provide potential targets for the therapy of NP. The function and mechanism of miR-125b-5p in regulating NP have been studied, aiming to find a potential therapeutic target for NP. METHODS: NP rat models were established by the chronic constriction injury (CCI) method. The paw withdrawal threshold and paw withdrawal latency were assessed to evaluate the establishment and recovery of rats. Highly aggressive proliferating immortalized (HAPI) micoglia cell, a rat microglia cell line, was treated with lipopolysaccharide (LPS). The M1/M2 polarization and inflammation were evaluated by enzyme-linked immunosorbent assay and western blotting. RESULTS: Decreasing miR-125b-5p and increasing SOX11 were observed in CCI rats and LPS-induced HAPI cells. Overexpressing miR-125b-5p alleviated mechanical allodynia and thermal hyperalgesia and suppressed inflammation in CCI rats. LPS induced M1 polarization and inflammation of HAPI cells, which was attenuated by miR-125b-5p overexpression. miR-125-5p negatively regulated the expression of SOX11 in CCI rats and LPS-induced HAPI cells. Overexpressing SOX11 reversed the protective effects of miR-125b-5p on mechanical pain in CCI rats and the polarization and inflammation in HAPI cells, which was considered the mechanism underlying miR-125b-5p. CONCLUSION: miR-125b-5p showed a protective effect on NP by regulating inflammation and polarization of microglia via negatively modulating SOX11.

Integrated ceRNAs regulating relationship and bioinformatics analysis to study the molecular mechanisms of the inhibition of puerarin on bladder cancer cell.

Based on previous experiments, we demonstrated puerarin inhibited the proliferation of BC T24 cells. To further explore the molecular mechanisms, whole transcriptome sequencing combined with bioinformatics analysis was performed. The results showed puerarin significantly inhibited T24 proliferation and pathway enrichment analysis of differentially expressed RNAs were mainly enriched in Cell cycle, PI3K/AKT, Ras family chromatin remodeling. lncRNAs and circRNAs may regulate miRNAs, thereby regulating the expression of ITGA1, PAK2 and UTRN. The predicted upstream transcription factor ERG and puerarin were well docked, which may be one of the underlying mechanisms by which puerarin inhibiting BC cells.

Role of the circRNA_34414/miR-6960a-5p/SIRT3 axis in postoperative delirium via CA1 Vglut1+ neurons in older mice.

AIMS: Postoperative delirium (POD) is a common neurological complication in elderly patients after anesthesia/surgery. The main purpose of this study is to explore the effect of circRNA-targeted miRNA regulating SIRT3 on mitochondrial function through ceRNA mechanism under the surgical model of tibial fracture and to further explore the potential mechanism of postoperative delirium mediated by circRNA, so as to provide new ideas for clinical diagnosis and prevention of POD. METHODS: The surgical model of tibial fracture under sevoflurane anesthesia caused acute delirium-like behavior in elderly mice. We observed that the decrease of SIRT3 and mitochondrial dysfunction was related to POD, and miRNA and circRNA (circRNA_34414) related to SIRT3 were further studied. Through luciferase and RAP, we observed that circRNA_34414, as a miRNA sponge, was involved in the regulation of SIRT3 expression. RESULTS: Postoperative delirium in elderly mice showed decreased expression of hippocampal circRNA_34414, increased expression of miR-6960-5p, decreased expression of SIRT3, and impaired mitochondrial membrane potential. Overexpression of circRNA_34414, or knockdown of miR-6960-5p, or overexpression of SIRT3 in hippocampal CA1 glutamatergic neurons significantly upregulated hippocampal SIRT3 expression, increased mitochondrial membrane potential levels, and significantly ameliorated postoperative delirium in aged mice; CircRNA_34414 ameliorates postoperative delirium in mice, possibly by targeting miR-6960-5p to upregulate SIRT3. CONCLUSIONS: CircRNA_34414 is involved in the improvement of postoperative delirium induced by anesthesia/surgery by upregulating SIRT3 via sponging miR-6960-5p.

Identifying autophagy-related mRNAs and potential ceRNA networks in meniscus degeneration based on RNA sequencing and experimental validation.

Purpose: The intimate connection between long noncoding RNA (lncRNA) and autophagy has been established in cartilage degeneration. However, their roles in meniscal degeneration remain ambiguous. This study aimed to identify the key autophagy-related lncRNA and its associated regulatory network in meniscal degeneration in the context of osteoarthritis (OA). Methods: RNA sequencing was performed to identify differentially expressed lncRNAs (DELs) and mRNAs (DEMs), which were then conducted to enrichment analyses using the DAVID database and Metascape. Autophagy-related DEMs were identified by combining DEMs with data from the Human Autophagy Database. Three databases were used to predict miRNA, and the DIANA LncBase Predicted database was utilized to predict miRNA-lncRNA interactions. Based on these predictions, comprehensive competitive endogenous RNA (ceRNA) network were constructed. The expression levels of the classical autophagy markers and autophagy-related ceRNA network were validated. Additionally, Gene Set Enrichment Analysis (GSEA) was performed using autophagy-related DEMs. Results: 310 DELs and 320 DEMs were identified, with five upregulated and one downregulated autophagy-related DEMs. Through reverse prediction of miRNA, paired miRNA-lncRNA interactions, and verification using RT-qPCR, two lncRNAs (PCAT19, CLIP1-AS1), two miRNA (has-miR-3680-3p and has-miR-4795-3p) and two mRNAs (BAG3 and HSP90AB1) were included in the constructed ceRNA regulatory networks. GSEA indicated that the increased expression of autophagy-related mRNAs inhibited glycosaminoglycan biosynthesis in the degenerative meniscus. Conclusion: This study presented the first construction of regulatory ceRNA network involving autophagy-related lncRNA-miRNA-mRNA interactions in OA meniscus. These findings offered valuable insights into the mechanisms underlying meniscal degeneration and provided potential targets for therapeutic intervention.

Whole transcriptome analysis identifies differentially expressed mRNA, miRNA and lncRNA associated with male sterility in the silkworm, Bombyx mori.

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.

A black phosphorus nanosheet-based RNA delivery system for prostate cancer therapy by increasing the expression level of tumor suppressor gene PTEN via CeRNA mechanism.

BACKGROUND: Prostate cancer (PCa) has a high incidence in men worldwide, and almost all PCa patients progress to the androgen-independent stage which lacks effective treatment measures. PTENP1, a long non-coding RNA, has been shown to suppress tumor growth through the rescuing of PTEN expression via a competitive endogenous RNA (ceRNA) mechanism. However, PTENP1 was limited to be applied in the treatment of PCa for the reason of rapid enzymatic degradation, poor intracellular uptake, and excessively long base sequence to be synthesized. Considering the unique advantages of artificial nanomaterials in drug loading and transport, black phosphorus (BP) nanosheet was employed as a gene-drug carrier in this study. RESULTS: The sequence of PTENP1 was adopted as a template which was randomly divided into four segments with a length of about 1000 nucleotide bases to synthesize four different RNA fragments as gene drugs, and loaded onto polyethyleneimine (PEI)-modified BP nanosheets to construct BP-PEI@RNA delivery platforms. The RNAs could be effectively delivered into PC3 cells by BP-PEI nanosheets and elevating PTEN expression by competitive binding microRNAs (miRNAs) which target PTEN mRNA, ultimately exerting anti-tumor effects. CONCLUSIONS: Therefore, this study demonstrated that BP-PEI@RNAs is a promising gene therapeutic platform for PCa treatment.

ETENLNC: An end to end lncRNA identification and analysis framework to facilitate construction of known and novel lncRNA regulatory networks.

Long non-coding RNAs (lncRNAs) play crucial roles in the regulation of gene expression and maintenance of genomic integrity through various interactions with DNA, RNA, and proteins. The availability of large-scale sequence data from various high-throughput platforms has opened possibilities to identify, predict, and functionally annotate lncRNAs. As a result, there is a growing demand for an integrative computational framework capable of identifying known lncRNAs, predicting novel lncRNAs, and inferring the downstream regulatory interactions of lncRNAs at the genome-scale. We present ETENLNC (End-To-End-Novel-Long-NonCoding), a user-friendly, integrative, open-source, scalable, and modular computational framework for identifying and analyzing lncRNAs from raw RNA-Seq data. ETENLNC employs six stringent filtration steps to identify novel lncRNAs, performs differential expression analysis of mRNA and lncRNA transcripts, and predicts regulatory interactions between lncRNAs, mRNAs, miRNAs, and proteins. We benchmarked ETENLNC against six existing tools and optimized it for desktop workstations and high-performance computing environments using data from three different species. ETENLNC is freely available on GitHub: https://github.com/EvolOMICS-TU/ETENLNC.

Identification of necroptosis-related genes in ankylosing spondylitis by bioinformatics and experimental validation.

The pathogenesis of ankylosing spondylitis (AS) remains unclear, and while recent studies have implicated necroptosis in various autoimmune diseases, an investigation of its relationship with AS has not been reported. In this study, we utilized the Gene Expression Omnibus database to compare gene expressions between AS patients and healthy controls, identifying 18 differentially expressed necroptosis-related genes (DENRGs), with 8 upregulated and 10 downregulated. Through the application of three machine learning algorithms-least absolute shrinkage and selection operation, support vector machine-recursive feature elimination and random forest-two hub genes, FASLG and TARDBP, were pinpointed. These genes demonstrated high specificity and sensitivity for AS diagnosis, as evidenced by receiver operating characteristic curve analysis. These findings were further supported by external datasets and cellular experiments, which confirmed the downregulation of FASLG and upregulation of TARDBP in AS patients. Immune cell infiltration analysis suggested that CD4+ T cells, CD8+ T cells, NK cells and neutrophils may be associated with the development of AS. Notably, in the group with high FASLG expression, there was a significant infiltration of CD8+ T cells, memory-activated CD4+ T cells and resting NK cells, with relatively less infiltration of memory-resting CD4+ T cells and neutrophils. Conversely, in the group with high TARDBP expression, there was enhanced infiltration of naïve CD4+ T cells and M0 macrophages, with a reduced presence of memory-resting CD4+ T cells. In summary, FASLG and TARDBP may contribute to AS pathogenesis by regulating the immune microenvironment and immune-related signalling pathways. These findings offer new insights into the molecular mechanisms of AS and suggest potential new targets for therapeutic strategies.

Comprehensive analysis of miRNAs-lncRNAs-mRNAs modules and ceRNA network in acute liver failure: Hsa-miR3175 and C-reactive protein determination.

Acute liver failure (ALF), also known as fulminant hepatitis, coagulation disorders, and worsening mental status. It has a poor prognosis and high mortality rate. Among these, the top 10 upregulated genes included GKA-DPA1, IGLL5, PLA2G7, CCL5, IGLJ, GUSBP11, RHOBT1, IGLL3P, CCL18, and ADRBK2. On the other hand, the top 10 downregulated genes were SLC6A1, PID1, AVPR1A, PP1R1A, ST3GAL6, TPST, ERO1LB, SLCO4C1, and KLF15. Furthermore, the DEGs were found to be enriched in processes related to LIAO metastasis and creighton endocrine therapy resistance. To explore the interactions among the DEGs, we constructed a PPI network. This network revealed 16 hub genes that play crucial roles in ALF pathogenesis. Within this network, hsa-mir-375 and hsa-mir-650 were identified as central nodes, indicating their potential importance in ALF. By identifying and analyzing the transcriptional-level ceRNA network, we have provided valuable insights into the etiology of ALF.

CircRNA and lncRNA-associated competing endogenous RNA networks in medulloblastoma: a scoping review.

BACKGROUND: Medulloblastoma is one of the common primary central nervous system (CNS) malignancies in pediatric patients. The main treatment is surgical resection preceded and/or followed by chemoradiotherapy. However, their serious side effects necessitate a better understanding of medulloblastoma biology to develop novel therapeutic options. MAIN BODY: Circular RNA (circRNA) and long non-coding RNA (lncRNA) regulate gene expression via microRNA (miRNA) pathways. Although growing evidence has highlighted the significance of circRNA and lncRNA-associated competing endogenous RNA (ceRNA) networks in cancers, no study has comprehensively investigated them in medulloblastoma. For this aim, the Web of Science, PubMed, Scopus, and Embase were systematically searched to obtain the relevant papers published before 16 September 2023, adhering to the PRISMA-ScR statement. HOTAIR, NEAT1, linc-NeD125, HHIP-AS1, CRNDE, and TP73-AS1 are the oncogenic lncRNAs, and Nkx2-2as is a tumor-suppressive lncRNA that develop lncRNA-associated ceRNA networks in medulloblastoma. CircSKA3 and circRNA_103128 are upregulated oncogenic circRNAs that develop circRNA-associated ceRNA networks in medulloblastoma. CONCLUSION: In summary, this study has provided an overview of the existing evidence on circRNA and lncRNA-associated ceRNA networks and their impact on miRNA and mRNA expression involved in various signaling pathways of medulloblastoma. Suppressing the oncogenic ceRNA networks and augmenting tumor-suppressive ceRNA networks can provide ample opportunities for medulloblastoma treatment.

Effect of ZIC2 on immune infiltration and ceRNA axis regulation in lung adenocarcinoma via bioinformatics and experimental studies.

OBJECTIVE: This study aimed to conclude the effect and mechanism of ZIC2 on immune infiltration in lung adenocarcinoma (LUAD). METHODS: Expression of ZIC2 in several kinds of normal tissues of TCGA data was analyzed and its correlation with the baseline characteristic of LUAD patients were analyzed. The immune infiltration analysis of LUAD patients was performed by CIBERSORT algorithm. The correlation analysis between ZIC2 and immune cell composition was performed. Additionally, the potential upstream regulatory mechanisms of ZIC2 were predicted to identify the possible miRNAs and lncRNAs that regulated ZIC2 in LUAD. In vitro and in vivo experiments were also conducted to confirm the potential effect of ZIC2 on cell proliferation and invasion ability of LUAD cells. RESULTS: ZIC2 expression was decreased in various normal tissues, but increased in multiple tumors, including LUAD, and correlated with the prognosis of LUAD patients. Enrichment by GO and KEGG suggested the possible association of ZIC2 with cell cycle and p53 signal pathway. ZIC2 expression was significantly correlated with T cells CD4 memory resting, Macrophages M1, and plasma cells, indicating that dysregulated ZIC2 expression in LUAD may directly influence immune infiltration. ZIC2 might be regulated by several different lncRNA-mediated ceRNA mechanisms. In vitro experiments validated the promotive effect of ZIC2 on cell viability and invasion ability of LUAD cells. In vivo experiments validated ZIC2 can accelerate tumor growth in nude mouse. CONCLUSION: ZIC2 regulated by different lncRNA-mediated ceRNA mechanisms may play a critical regulatory role in LUAD through mediating the composition of immune cells in tumor microenvironment.

Long non-coding RNA HOTTIP promotes renal cell carcinoma progression through the regulation of the miR-506 pathway.

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.

Integrated Analysis of Transcriptome Profiles and lncRNA-miRNA-mRNA Competing Endogenous RNA Regulatory Network to Identify Biological Functional Effects of Genes and Pathways Associated with Johne's Disease in Dairy Cattle.

Paratuberculosis or Johne's disease (JD), a chronic granulomatous gastroenteritis caused by Mycobacterium avium subsp. paratuberculosis (MAP), causes huge economic losses and reduces animal welfare in dairy cattle herds worldwide. At present, molecular mechanisms and biological functions involved in immune responses to MAP infection of dairy cattle are not clearly understood. Our purpose was to integrate transcriptomic profiles and competing endogenous RNA (ceRNA) network analyses to identify key messenger RNAs (mRNAs) and regulatory RNAs involved in molecular regulation of peripheral blood mononuclear cells (PBMCs) for MAP infection in dairy cattle. In total, 28 lncRNAs, 42 miRNAs, and 370 mRNAs were identified by integrating gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. In this regard, we identified 21 hub genes (CCL20, CCL5, CD40, CSF2, CXCL8, EIF2AK2, FOS, IL10, IL17A, IL1A, IL1B, IRF1, MX2, NFKB1, NFKBIA, PTGS2, SOCS3, TLR4, TNF, TNFAIP3, and VCAM1) involved in MAP infection. Furthermore, eight candidate subnets with eight lncRNAs, 29 miRNAs, and 237 mRNAs were detected through clustering analyses, whereas GO enrichment analysis of identified RNAs revealed 510, 22, and 11 significantly enriched GO terms related to MAP infection in biological process, molecular function, and cellular component categories, respectively. The main metabolic-signaling pathways related to MAP infection that were enriched included the immune system process, defense response, response to cytokine, leukocyte migration, regulation of T cell activation, defense response to bacterium, NOD-like receptor, B cell receptor, TNF, NF-kappa B, IL-17, and T cell receptor signaling pathways. Contributions of transcriptome profiles from MAP-positive and MAP-negative sample groups plus a ceRNA regulatory network underlying phenotypic differences in the intensity of pathogenicity of JD provided novel insights into molecular mechanisms associated with immune system responses to MAP infection in dairy cattle.

Identification of potential therapeutic target SPP1 and related RNA regulatory pathway in keloid based on bioinformatics analysis.

OBJECTIVE: To explore the complex mechanisms of keloid, new approaches have been developed by different strategies. However, conventional treatment did not significantly reduce the recurrence rate. This study aimed to identify new biomarkers and mechanisms for keloid progression through bioinformatics analyses. METHODS: In our study, microarray datasets for keloid were downloaded from the GEO database. Differentially expressed genes (DEGs) were identified by R software. Multiple bioinformatics tools were used to identify hub genes, and reverse predict upstream miRNAs and lncRNA molecules of target hub genes. Finally, the total RNA-sequencing technique and miRNA microarray were combined to validate the identified genes. RESULTS: Thirty-one DEGs were screened out and the upregulated hub gene SPP1 was finally identified, which was consistent with our RNA-sequencing analysis results and validation dataset. In addition, a ceRNA network of mRNA (SPP1)-miRNA (miR-181a-5p)-lncRNA (NEAT1, MALAT1, LINC00667, NORAD, XIST and MIR4458HG) was identified by the bioinformatics databases. The results of our miRNA microarray showed that miR-181a-5p was upregulated in keloid, also we found that the lncRNA NEAT1 could affect keloid progression by retrieving the relevant literature. CONCLUSIONS: We speculate that SPP1 is a potential candidate biomarker and therapeutic target for patients with keloid, and NEAT1/miR-181a-5p/SPP1 might be the RNA regulatory pathway that regulates keloid formation.

Identify new biomarkers in keloid, potentially improve disease diagnosis and treatment.Through a variety of bioinformatics analysis tools, we found that the miRNA pathway NEAT1/miR-181a-5p/SPP1 may participant in controlling disease progression in the keloid.Providing insight into the mechanisms of disease development in the keloid at the transcriptome level.