LincRNA-EPS Promotes Proliferation of Aged Dermal Fibroblast by Inducing CCND1.

The aging process is linked to numerous cellular changes, among which are modifications in the functionality of dermal fibroblasts. These fibroblasts play a crucial role in sustaining the healing of skin wounds. Reduced cell proliferation is a hallmark feature of aged dermal fibroblasts. Long intergenic non-coding RNA (lincRNAs), such as LincRNA-EPS (Erythroid ProSurvival), has been implicated in various cellular processes. However, its role in aged dermal fibroblasts and its impact on the cell cycle and its regulator, Cyclin D1 (CCND1), remains unclear. Primary dermal fibroblasts were isolated from the skin of 17-week-old (young) and 88-week-old (aged) mice. Overexpression of LincRNA-EPS was achieved through plasmid transfection. Cell proliferation was detected using the MTT assay. Real-time PCR was used to quantify relative gene expressions. Our findings indicate a noteworthy decline in the expression of LincRNA-EPS in aged dermal fibroblasts, accompanied by reduced levels of CCND1 and diminished cell proliferation in these aging cells. Significantly, the overexpression of LincRNA-EPS in aged dermal fibroblasts resulted in an upregulation of CCND1 expression and a substantial increase in cell proliferation. Mechanistically, LincRNA-EPS induces CCND1 expression by sequestering miR-34a, which was dysregulated in aged dermal fibroblasts, and directly targeting CCND1. These outcomes underscore the crucial role of LincRNA-EPS in regulating CCND1 and promoting cell proliferation in aged dermal fibroblasts. Our study provides novel insights into the molecular mechanisms underlying age-related changes in dermal fibroblasts and their implications for skin wound healing. The significant reduction in LincRNA-EPS expression in aged dermal fibroblasts and its ability to induce CCND1 expression and enhance cell proliferation highlight its potential as a therapeutic target for addressing age-related skin wound healing.

Keratinocyte-derived small extracellular vesicles delay diabetic wound healing by triggering fibroblasts autophagy.

Keratinocyte and fibroblast dysfunctions contribute to delayed healing of diabetic wounds. Small extracellular vesicles (sEV) are key mediators of intercellular communication and are involved in the pathogenesis of several diseases. Recent findings suggest that sEV derived from high-glucose-treated keratinocyte (HaCaT-HG-sEV) can transport LINC01435 to inhibit tube formation and migration of HUVECs, thereby delaying wound healing. This study aimed to elucidate sEV-related communication mechanisms between keratinocytes and fibroblasts during diabetic wound healing. HaCaT-HG-sEV treatment and LINC01435 overexpression significantly decreased fibroblast collagen level and migration ability but significantly increased fibroblast autophagy. However, treatment with an autophagy inhibitor suppressed LINC01435 overexpression-induced decrease in collagen levels in fibroblasts. In diabetic mice, HaCaT-HG-sEV treatment decreased collagen levels and increased the expression of the autophagy-related proteins Beclin-1 and LC3 at the wound site, thereby delaying wound healing. Conclusively, LINC01435 in keratinocyte-derived sEV activates fibroblast autophagy and reduces fibroblast collagen synthesis, leading to impaired diabetic wound healing.

Diabetic foot ulcers are a serious complication of diabetes and can lead to amputation and death. Therefore, it is crucial to comprehensively elucidate the mechanisms of delayed diabetic wound healing, with emphasis on the role of keratinocyte-derived small extracellular vesicles. In vivo and in vitro experiments showed that keratinocyte-derived small extracellular vesicles suppressed diabetic wound healing, which is partly attributed to the effects of their content (LINC01435) in fibroblasts. This study suggests that LINC01435 could be targeted to regulate diabetic wound healing.

Generation of New ß-Conglycinin-Deficient Soybean Lines by Editing the lincRNA lincCG1 Using the CRISPR/Cas9 System.

Soybean ß-conglycinin is a major allergen that adversely affects the nutritional properties of soybean. Soybean deficient in ß-conglycinin is associated with low allergenicity and high nutritional value. Long intergenic noncoding RNAs (lincRNAs) regulate gene expression and are considered important regulators of essential biological processes. Despite increasing knowledge of the functions of lincRNAs, relatively little is known about the effects of lincRNAs on the accumulation of soybean ß-conglycinin. The current study presents the identification of a lincRNA lincCG1 that was mapped to the intergenic noncoding region of the ß-conglycinin α-subunit locus. The full-length lincCG1 sequence was cloned and found to regulate the expression of soybean seed storage protein (SSP) genes via both cis- and trans-acting regulatory mechanisms. Loss-of-function lincCG1 mutations generated using the clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) system led to the deficiency of the allergenic α'-, α-, and ß-subunits of soybean ß-conglycinin as well as higher content of proteins, sulfur-containing amino acids, and free arginine. The dominant null allele LincCG1, and consequently, the ß-conglycinin-deficient phenotype associated with the lincCG1-gene-edited line was stably inherited by the progenies in a Mendelian fashion. The dominant null allele LincCG1 may therefore be exploited for engineering/developing novel hypoallergenic soybean varieties. Furthermore, Cas9-free and ß-conglycinin-deficient homozygous mutant lines were obtained in the T1 generation. This study is the first to employ the CRISPR/Cas9 technology for editing a lincRNA gene associated with the soybean allergenic protein ß-conglycinin. Moreover, this study reveals that lincCG1 plays a crucial role in regulating the expression of the ß-conglycinin subunit gene cluster, besides highlighting the efficiency of employing the CRISPR/Cas9 system for modulating lincRNAs, and thereby regulating soybean seed components.

The oxidative stress-associated long non-coding RNAs in pancreatic cancer.

PURPOSE: A lot of people are dying from pancreatic cancer (PC) annually. The early detection of this cancer is particularly challenging due to the fact that symptoms tend to appear in advanced stages. It has been suggested that oxidative stress may play a role in the development of PC. Several genes regulate this process, including long noncoding RNAs (lncRNAs). There is no comprehensive study on the expression pattern of lncRNAs related to oxidative stress in PC patients. In the present case-control study, we quantified levels of oxidative stress-associated lncRNAs in PC patients versus healthy controls. PATIENTS AND METHODS: In the present study, we investigated the expression levels of lincRNA-p21, LUCAT, RMST, FOXD3-AS1, and MT1DP lncRNAs in the peripheral blood mononuclear cells (PBMCs) of 53 â€‹PC patients and 50 healthy controls. The association between lncRNA expression and clinical and pathological characteristics was also evaluated. RESULTS: The expression of lincRNA-P21 and rhabdomyosarcoma 2-associated transcript (RMST) lncRNAs in PC patients has significantly decreased. Expression of lncRNA RMST was significantly higher in TNM stage III-IV patients in comparison to TNM stage I-II patients. In addition, a significant positive association was recognized between candidate lncRNA expression, and finally, the AUC values of the expression levels of lincRNA-p21 and RMST were 0.60 and 0.61, respectively. CONCLUSIONS: Altogether, our study suggests a possible role of lincRNA-p21 and RMST lncRNAs in the etiology of PC pathobiology, and their biomarker role may be understood in future studies.

lincRNA00907 promotes NASH progression by targeting miRNA-942-5p/TAOK1.

OBJECTIVE: The study aims to examine the involvement of lincRNA00907 in the advancement of non-alcoholic steatohepatitis (NASH). METHODS: The examination was conducted to assess the expression of linc00907 in liver tissues from NASH patients and healthy individuals. High-fat diets induced NASH in mouse models, while palmitic acid/oleic acid treatment was used to create in vitro cell models. Various techniques, such as qRT-PCR, Oil Red O staining and gene knockdown/overexpression, were used to assess the impact of linc00907 on genes related to lipid metabolism and immunity, as well as intracellular lipid accumulation. Furthermore, dual-luciferase reporter assays were carried out to confirm the connection between miRNA-942-5p and linc00907 or TAOK1 mRNA. RESULTS: Linc00907 was found to be significantly upregulated in both NASH patients and NASH mouse models. Overexpression of linc00907 led to an increase in intracellular lipid accumulation, while knockdown of linc00907 resulted in decreased lipid content. It was found that miRNA-942-5p binds with linc00907, and their interaction was confirmed in dual-luciferase reporter assays. Additionally, TAOK1 was predicted to be a downstream target of miRNA-942-5p, and the upregulation of TAOK1 due to linc00907 was reversed by miRNA-942-5p overexpression. linc00907 overexpression reduces apoptosis but can be reversed by TAOK1 knockdown. The reduction of TAOK1 counteracted the impact of linc00907 on gene expression associated with lipid metabolism and immunity, as well as on the accumulation of intracellular lipids. CONCLUSIONS: Our research suggests that linc00907 functions as a competitive endogenous RNA (ceRNA) by sequestering miRNA-942-5p, thus increasing the expression of TAOK1 and encouraging lipid accumulation in hepatocytes, leading to the aggravation of NASH development. Targeting the linc00907/miRNA-942-5p/TAOK1 axis may hold therapeutic potential for the treatment of NASH.

Long Noncoding RNA VLDLR-AS1 Levels in Serum Correlate with Combat-Related Chronic Mild Traumatic Brain Injury and Depression Symptoms in US Veterans.

More than 75% of traumatic brain injuries (TBIs) are mild (mTBI) and military service members often experience repeated combat-related mTBI. The chronic comorbidities concomitant with repetitive mTBI (rmTBI) include depression, post-traumatic stress disorder or neurological dysfunction. This study sought to determine a long noncoding RNA (lncRNA) expression signature in serum samples that correlated with rmTBI years after the incidences. Serum samples were obtained from Long-Term Impact of Military-Relevant Brain-Injury Consortium Chronic Effects of Neurotrauma Consortium (LIMBIC CENC) repository, from participants unexposed to TBI or who had rmTBI. Four lncRNAs were identified as consistently present in all samples, as detected via droplet digital PCR and packaged in exosomes enriched for CNS origin. The results, using qPCR, demonstrated that the lncRNA VLDLR-AS1 levels were significantly lower among individuals with rmTBI compared to those with no lifetime TBI. ROC analysis determined an AUC of 0.74 (95% CI: 0.6124 to 0.8741; p = 0.0012). The optimal cutoff for VLDLR-AS1 was ≤153.8 ng. A secondary analysis of clinical data from LIMBIC CENC was conducted to evaluate the psychological symptom burden, and the results show that lncRNAs VLDLR-AS1 and MALAT1 are correlated with symptoms of depression. In conclusion, lncRNA VLDLR-AS1 may serve as a blood biomarker for identifying chronic rmTBI and depression in patients.

Key Non-coding Variants in Three Neuroapoptosis and Neuroinflammation-Related LncRNAs Are Protectively Associated with Susceptibility to Parkinson's Disease and Some of Its Clinical Features.

Research findings show that genetic susceptibility to sporadic Parkinson's disease (PD), a common neurodegenerative disorder, is determined through gene variation of loci involved in its development and pathogenesis. A growing body of strong evidence has revealed that dysfunction of long non-coding RNAs (lncRNAs) plays key roles in the pathogenesis and progression of PD through impairing neuronal signaling pathways, but little is known about the relationship between their variants and PD susceptibility. In this research, we intended to study the relationship between functional SNPs rs12826786C>T, rs3200401C>T, and rs6931097G>A in the key lncRNAs stimulating neuroapoptosis and neuroinflammation in PD, including HOTAIR, MALAT1, and lincRNA-P21, respectively, with susceptibility to PD as well as its clinical symptoms.The population of this study consisted of 240 individuals, including 120 controls and 120 cases, and the sample taken from them was peripheral blood. Genotyping of the target SNPs was done using PCR-RFLP. We found that the healthy individuals carry more T allele of MALAT1-rs3200401C>T compared to the patients (P= 0.019). Furthermore, it was observed that in the dominant genetic model, subjects with genotypes carrying the T allele have a lower risk of PD (OR= 0.530; CI= 0.296-0.950; P= 0.033). Regarding the lincRNA-P21-rs6931097G>A, we observed a significant protective relationship between its GA (OR= 0.144; CI= 0.030-0.680; P= 0.014) and AA (OR= 0.195; CI= 00.047-0.799; P= 0.023) genotypes with the manifestation of tremor and bradykinesia symptoms, respectively. Furthermore, the findings indicated that the minor TT genotype of HOTAIR-rs12826786C>T was significantly associated with a reduced risk of bradykinesia symptoms (OR= 0.147; CI= 0.039-0.555; P= 0.005). Collectively, these findings suggest that MALAT1-rs3200401C>T may be an important lncRNA SNP against the development of PD, while the other two SNPs show protective effects on the clinical manifestations of PD in a way that lincRNA-P21-rs6931097G>A has a protective effect against the occurrence of tremor and bradykinesia symptoms in PD patients, and HOTAIR -rs12826786C>T indicates a protective effect against the display of bradykinesia feature. Therefore, they can have valuable potential as biomarkers for clinical evaluations of this disease.

LINC01579-204 involved in the development of Hirschsprung's disease maybe by regulating the expression of miR-203a-3p and NEFL.

BACKGROUND: Hirschsprung's disease (HD) is a rare congenital digestive tract malformation in children. Roles of long non-coding RNAs (lncRNAs) are highlighted in various human diseases. However, knowledge on lncRNAs in HD is still limited. METHODS: The profile of lncRNAs in 8 pairs of normal and stenosed intestinal tissue of HD patients were obtained using microarray analysis. Base on bioinformatics analysis, the level of selected LINC01579-204, NEFL and miR-203a-3p was detected by qRT-PCR in 36 pairs of normal and stenosed intestinal tissue of HD patients. Then the predictive accuracy of LINC01579-204, miR-203a-3p and NEFL level to evaluate the progression of HD patients was analyzed with receiver operating characteristic curve (ROC). RESULTS: A total of 90 differentially expressed lncRNAs were detected in normal and stenosed intestinal tissue of HD patients (|fold change| ≥ 1.5, p < 0.05). The level of LINC01579-204 and NEFL decreased and miR-203a-3p increased significantly in 36 pairs of stenosed intestinal tissue of HD patients compared to the control. A notable positive correlation was identified between LINC01579-204 and NEFL (r = 0.9681, p < 0.0001). Areas under the ROC curve of the LINC01579-204, miR-203a-3p and NEFL signature were 0.715, 0.777 and 0.829, respectively. CONCLUSIONS: LINC01579-204, miR-203a-3p, and NEFL are predicted to play important roles in the progression of HD. LINC01579-204, miR-203a-3p and NEFL had a significant overall predictive ability to identify progression of HD patients. The novel experimental and bioinformatic results achieved in this study may provide new insights into the molecular of HD.

The Intergenic Type LncRNA (LINC RNA) Faces in Cancer with In Silico Scope and a Directed Lens to LINC00511: A Step toward ncRNA Precision.

BACKGROUND: Long intergenic non-coding RNA, is one type of lncRNA, exerting various cellular activities, as does ncRNA, including the regulation of gene expression and chromatin remodeling. The abnormal expression of lincRNAs can induce or suppress carcinogenesis. MAIN BODY: LincRNAs can regulate cancer progression through different mechanisms and are considered as potential drug targets. Genetic variations such as single nucleotide polymorphisms (SNPs) in lincRNAs may affect gene expression and messenger ribonucleic acid (mRNA) stability. SNPs in lincRNAs have been found to be associated with different types of cancer, as well. Specifically, LINC00511 has been known to promote the progression of multiple malignancies such as breast cancer, colorectal cancer, lung cancer, hepatocellular carcinoma, and others, making it a promising cancer prognostic molecular marker. CONCLUSION: LincRNAs have been proved to be associated with different cancer types through various pathways. Herein, we performed a comprehensive literature and in silico databases search listing lncRNAs, lincRNAs including LINC00511, lncRNAs' SNPs, as well as LINC00511 SNPs in different cancer types, focusing on their role in various cancer types and mechanism(s) of action.

LincRNA-P21 knockdown facilitates esophageal squamous cell carcinoma cell progression by upregulating cadherin 5 via YTH domain containing 1.

LincRNA-P21 is a tumor suppressor in esophageal squamous cell carcinoma (ESCC). Cell adhesion modules play vital roles in cell-cell and cell-extracellular matrix (ECM) interactions and malignant cancer progression. In this study, we investigate whether lincRNA-P21 exerts its functions by regulating the cell adhesion molecule cadherin 5 (CDH5) in ESCC. Moreover, the RNA binding protein (RBP) mediators of lincRNA-P21 and CDH5 are further examined. Cell viability, growth and migratory ability are assessed by calcein-AM/PI double staining, CCK-8, EdU, Transwell, and wound healing assays. The expression of collagen I and fibronectin is examined by immunofluorescence (IF). LincRNA-P21 and CDH5 are quantified by RT-qPCR and western blot analysis. Potential lincRNA-P21 targets are identified by RNA sequencing. RBPs that can interact with lincRNA-P21 and CDH5 are identified by RNA immunoprecipitation (RIP) assay. LincRNA-P21 knockdown increases cell viability, growth, cell migration, and collagen I and fibronectin expression in ESCC cells. LincRNA-P21 depletion induces the dysregulation of 316 genes, including CDH5, in TE-1 cells. CDH5 is identified as a downstream molecule of lincRNA-P21 given its close correlation with cell adhesion, ECM reconstruction, and cancer progression. LincRNA-P21 exerts its functions by negatively regulating CDH5 expression. YTH domain containing 1 (YTHDC1) mediates the regulatory effect of lincRNA-P21 on CDH5. LincRNA-P21 knockdown elevates cell viability and growth, promotes cell migration, and induces ECM reorganization by upregulating CDH5 via RBP YTHDC1 in ESCC.

Actinidia eriantha polysaccharide exerts adjuvant activity by targeting linc-AAM.

Actinidia eriantha polysaccharide (AEPS) is a potent adjuvant with dual Th1 and Th2 potentiating activity. linc-AAM has been previously proved to facilitate the expression of immune response genes (IRGs) in AEPS-activated RAW264.7 macrophages. However, its role in mediating adjuvant activity of AEPS remains to be elucidated. In this study, bone marrow-derived macrophages (BMDMs) from wide-type (WT) and linc-AAM knockout C57BL/6J mice treated with AEPS were subjected to transcriptome sequencing and bioinformatic analysis. linc-AAM deficiency inhibited M1 and M2 immune responses in BMDMs induced by AEPS. In mechanisms, AEPS facilitated the expression of IRGs and activated BMDMs through NF-κB-linc-AAM-JAK/STAT axis. Furthermore, linc-AAM knockout inhibited cytokine and chemokine production, immune cell recruitment as well as immune cell migration to draining lymph nodes at peritoneal cavity in mice induced by AEPS. More importantly, linc-AAM deletion reduced the adjuvant activity of APES on antigen-specific cellular and humoral immune responses to ovalbumin in mice. This study has for the first time demonstrated the role of lncRNAs in regulating the adjuvant activity of polysaccharides and its mechanisms. These findings expanded current knowledge on the mechanism of action of adjuvant and provide a new target for the design and development of vaccine adjuvants.

Identification of a novel immune-related long noncoding RNA in carp primary macrophages associated with bisphenol A' s immunoregulatory effects.

Increasing evidence suggests that long non-coding RNAs (lncRNAs) play pivotal roles in various biological processes. However, current studies on lncRNAs mostly focus on mammalian species, with little research on the functional roles of lncRNAs in teleost fish. Here, we identified a novel intergenic lncRNA (linc-93.2) in the head kidney primary macrophages of common carp (Cyprinus carpio) after exposure to a typical environmental endocrine disrupting chemical, bisphenol A (BPA). As a result, linc-93.2 was more than 3,619 bp in length and predominantly localized to the nucleus of primary macrophages other than cytoplasm, with the highest expression level in spleen followed by head kidney among different organs. Bioinformatic analysis predicted a cis-target gene, dennd1b, and 20 trans-target genes including hsp70, gna13 and rasgap, were potentially regulated by linc-93.2; NFκB and estrogen receptor (ERα) binding sites were located in the promoter region upstream of its transcription start site, which together suggested the involvement of linc-93.2 in immune and neurological functions in fish. Based on that, the expression level of linc-93.2 was determined in macrophages following acute lipopolysaccharide (LPS) and BPA treatments, both of which significantly induced linc-93.2 and IL-1ß expression in cells. Moreover, a NF-κB inhibitor PDTC significantly reduced linc-93.2 expression in macrophages, but co-exposure of macrophages to PDTC with BPA or LPS could significantly rescue linc-93.2 expression, consistent with the observation on that LPS or BPA alone significantly induced both linc-93.2 and its target gene expression. Interestingly, linc-93.2 and its target gene expression was significantly suppressed by an ER antagonist ICI 182,780, however, the co-exposure of macrophages to ICI 182,780 with BPA failed to attenuate their declined expression. Overall, the current study demonstrated that linc-93.2, a novel immune-related lncRNA, may participate in the immune processes of common carp macrophages via the NF-κB and ER pathway. The results presented in this study enhance our understanding of the immunotoxin mechanisms of BPA in teleost fish.

lincRNA RP24-315D19.10 promotes endometrial decidualization via upregulation of hnRNPA2B1.

Decidualization is a critical process for successful pregnancy. Disorders in this process are tightly associated with adverse pregnancy outcomes including spontaneous abortion. However, the potential molecular mechanisms of lncRNAs underlying this process are yet to be fully elucidated. In this study, we utilized RNA sequencing (RNA-seq) to identify differentially expressed lncRNAs during endometrial decidualization with a pregnant mouse model. Based on RNA-seq analysis, weighted gene co-expression network analysis (WGCNA) was performed to construct the lncRNA-mRNA co-expression network and to identify decidualization-associated hub lncRNAs. Through comprehensive screening and validation, we identified a novel lncRNA, RP24-315D19.10 and studied its function in primary mouse endometrial stromal cells (mESCs). lncRNA RP24-315D19.10 was highly expressed during decidualization. Knockdown of RP24-315D19.10 significantly inhibited mESCs decidualization in vitro. Mechanistically, RNA pull-down and RNA immunoprecipitation assays indicated that cytoplasmic RP24-315D19.10 could bind to hnRNPA2B1, thereby upregulating hnRNPA2B1 expression. Site-directed mutagenesis followed by biolayer interferometry analysis additionally illustrated that hnRNPA2B1 protein specifically bound to the ~-142ccccc~-167 region of the RP24-315D19.10 sequence. hnRPA2B1 deficiency impairs mESCs decidualization in vitro and we found that the inhibition in decidualization caused by RP24-315D19.10 knockdown was rescued by hnRNPA2B1 overexpression. Moreover, the expression of hnRNPA2B1 in spontaneous abortion women with deficient decidualization was significantly lower than that in healthy individuals, suggesting that hnRNPA2B1 may be involved in the development and progression of spontaneous abortion caused by decidualization failure. Collectively, our study indicates RP24-315D19.10 is a critical regulator for endometrial decidualization and RP24-315D19.10-regulated hnRNPA2B1 might be a new mark of decidualization-related spontaneous abortion.

LincRNA PRNCR1 activates the Wnt/ß-catenin pathway to drive the deterioration of hepatocellular carcinoma via regulating miR-411-3p/ZEB1 axis.

Hepatocellular carcinoma (HCC) is an intractable malignant disease with high incidence rate annually. LincRNA PRNCR1 has been confirmed as a tumor supporter, while its functions in HCC remain unclear. This study aims to explore the mechanism of LincRNA PRNCR1 in hepatocellular carcinoma. The qRT-PCR was applied to the quantification of non-coding RNAs. Cell counting Kit-8 (CCK-8), Transwell assay and flow cytometry assay were applied to reflect the change in the phenotype of HCC cells. Moreover, the databases including Targetscan and Starbase and dual-luciferase reporter assay were applied to investigate the interaction of the genes. The western blot was applied to detect the abundance of proteins and the activity of the related pathways. Elevated LincRNA PRNCR1 was dramatically upregulated in HCC pathological samples and cell lines. MiR-411-3p served as a target of LincRNA PRNCR1, and decreased miR-411-3p was found in the clinical samples and cell lines. LincRNA PRNCR1 downregulation could induce the expression of miR-411-3p, and LincRNA PRNCR1 silence could impede the malignant behaviors via increasing the abundance of miR-411-3p. Zinc finger E-box binding homeobox 1 (ZEB1) was confirmed as a target of miR-411-3p, which remarkably upregulated in HCC cells, and ZEB1 upregulation could significantly rescue the effect of miR-411-3p on malignant behaviors of HCC cells. Moreover, LincRNA PRNCR1 was confirmed to involve the Wnt/ß-catenin pathway via regulating miR-411-3p/ZEB1 axis. This study suggested that LincRNA PRNCR1 could drive the malignant progression of HCC via regulating miR-411-3p/ZEB1 axis.

Altered Lnc-EGFR, SNHG1, and LincRNA-Cox2 Profiles in Patients with Relapsing-Remitting Multiple Sclerosis: Impact on Disease Activity and Progression.

Relapsing-remitting multiple sclerosis (RRMS) is the most prevalent MS subtype. Ample evidence has indicated that long noncoding RNAs (lncRNAs) are crucial players in autoimmune and inflammatory disorders. This study investigated the expression of lnc-EGFR, SNHG1, and lincRNA-Cox2 in RRMS patients during active relapses and in remission. Additionally, the expression of FOXP3, a master transcription factor for regulatory T cells, and NLRP3-inflammasome-related genes were determined. Relationships between these parameters and MS activity and annualized relapse rate (ARR) were also evaluated. The study included 100 Egyptian participants: 70 RRMS patients (35 during relapse and 35 in remission) and 30 healthy controls. RRMS patients showed significant downregulation of lnc-EGFR and FOXP3 and dramatic upregulation of SNHG1, lincRNA-Cox2, NLRP3, ASC, and caspase-1 compared to controls. Lower serum TGF-ß1 and elevated IL-1ß levels were observed in RRMS patients. Notably, patients during relapses displayed more significant alterations than those in remission. Lnc-EGFR was positively correlated with FOXP3 and TGF-ß1 and negatively correlated with ARR, SNHG1, lincRNA-Cox2, and NLRP3 inflammasome components. Meanwhile, SNHG1 and lincRNA-Cox2 were positively correlated with ARR, NLRP3, ASC, caspase-1, and IL-1ß. Excellent diagnostic performance for lnc-EGFR, FOXP3, and TGF-ß1 was demonstrated, while all biomarkers exhibited strong prognostic potential for predicting relapses. Finally, the differential expression of lnc-EGFR, SNHG1, and lincRNA-Cox2 in RRMS patients, especially during relapses, suggests their involvement in RRMS pathogenesis and activity. Correlation between their expression and ARR implies relationships to disease progression. Our findings also highlight their promising roles as biomarkers for RRMS.

Inhibition of lincRNA-Cox2 alleviates apoptosis and inflammatory injury of lipopolysaccharide-stimulated human bronchial epithelial cells via the Nrf2/HO-1 axis.

This study mainly explored the role and mechanism of lincRNA-Cox2 in inflammatory injury of human bronchial epithelial cells. BEAS-2B cells were stimulated with lipopolysaccharide to establish an in vitro inflammatory injury model. Real-time polymerase chain reaction was used to detect lincRNA-Cox2 expression in LPS-stimulated BEAS-2B. Cell viability and apoptosis of cells were assessed using CCK-8 and Annexin V-PI double staining. The contents of inflammatory factors were determined by enzyme-linked immunosorbent assay kits. The protein levels of nuclear factor erythrocyte 2-related factor 2 and haem oxygenase 1 protein levels were measured by Western blot. The results showed that lincRNA-Cox2 was upregulated in LPS-stimulated BEAS-2B cells. lincRNA-Cox2 knockdown inhibited apoptosis and the release of tumour necrosis factor alpha, interleukin 1beta (IL-1ß), IL-4, IL-5, and IL-13 in BEAS-2B cells. lincRNA-Cox2 overexpression had the opposite effect. lincRNA-Cox2 knockdown also inhibited LPS-induced oxidative damage in BEAS-2B cells. Further mechanistic studies showed that inhibition of lincRNA-Cox2 upregulated the levels of Nrf2 and HO-1, and si-Nrf2 reversed the effects of si-lincRNA-Cox2. In conclusion, lincRNA-Cox2 knockdown inhibited BEAS-2B apoptosis and the level of inflammatory factors by activating the Nrf2/HO-1 pathway.

Non-coding RNA in the wiring and remodeling of neural circuits.

The brain constantly adapts to changes in the environment, a capability that underlies memory and behavior. Long-term adaptations require the remodeling of neural circuits that are mediated by activity-dependent alterations in gene expression. Over the last two decades, it has been shown that the expression of protein-coding genes is significantly regulated by a complex layer of non-coding RNA (ncRNA) interactions. The aim of this review is to summarize recent discoveries regarding the functional involvement of ncRNAs during different stages of neural circuit development, activity-dependent circuit remodeling, and circuit maladapations underlying neurological and neuropsychiatric disorders. In addition to the intensively studied microRNA (miRNA) family, we focus on more recently added ncRNA classes, such as long ncRNAs (lncRNAs) and circular RNAs (circRNAs), and discuss the complex regulatory interactions between these different RNAs. We conclude by discussing the potential relevance of ncRNAs for cell-type and -state-specific regulation in the context of memory formation, the evolution of human cognitive abilities, and the development of new diagnostic and therapeutic tools in brain disorders.

The Role of LincRNA-EPS/Sirt1/Autophagy Pathway in the Neuroprotection Process by Hydrogen against OGD/R-Induced Hippocampal HT22 Cells Injury.

Cerebral ischemia/reperfusion (CI/R) injury causes high disability and mortality. Hydrogen (H2) enhances tolerance to an announced ischemic event; however, the therapeutic targets for the effective treatment of CI/R injury remain uncertain. Long non-coding RNA lincRNA-erythroid prosurvival (EPS) (lincRNA-EPS) regulate various biological processes, but their involvement in the effects of H2 and their associated underlying mechanisms still needs clarification. Herein, we examine the function of the lincRNA-EPS/Sirt1/autophagy pathway in the neuroprotection of H2 against CI/R injury. HT22 cells and an oxygen-glucose deprivation/reoxygenation (OGD/R) model were used to mimic CI/R injury in vitro. H2, 3-MA (an autophagy inhibitor), and RAPA (an autophagy agonist) were then administered, respectively. Autophagy, neuro-proinflammation, and apoptosis were evaluated by Western blot, enzyme-linked immunosorbent assay, immunofluorescence staining, real-time PCR, and flow cytometry. The results demonstrated that H2 attenuated HT22 cell injury, which would be confirmed by the improved cell survival rate and decreased levels of lactate dehydrogenase. Furthermore, H2 remarkably improved cell injury after OGD/R insult via decreasing pro-inflammatory factors, as well as suppressing apoptosis. Intriguingly, the protection of H2 against neuronal OGD/R injury was abolished by rapamycin. Importantly, the ability of H2 to promote lincRNA-EPS and Sirt1 expression and inhibit autophagy were abrogated by the siRNA-lincRNA-EPS. Taken together, the findings proved that neuronal cell injury caused by OGD/R is efficiently prevented by H2 via modulating lincRNA-EPS/Sirt1/autophagy-dependent pathway. It was hinted that lincRNA-EPS might be a potential target for the H2 treatment of CI/R injury.

Male-specific roles of lincRNA in C. elegans fertility.

The testis is the mammalian tissue with the highest expression levels of long intergenic non-coding RNAs (lincRNAs). However, most in vivo models have not found significant reductions in male fertility when highly expressed lincRNA genes were removed. This suggests that certain lincRNAs may act redundantly or lack functional roles. In the genome of the nematode Caenorhabditis elegans, there is an order of magnitude fewer lincRNA genes than in mammals. This characteristic lowers the potential for redundancy, making it an ideal model to test these possibilities. We identified five highly and dynamically expressed lincRNAs in male C. elegans gonads and quantified the fertility of worm strains in which these genes were removed. In contrast to the hermaphrodites of deletion strains, which exhibited no significant reductions in broods, smaller brood sizes were observed in the progeny of males of three of the lincRNA deleted strains. This demonstrates reduced male fertility in worms with those genes removed. Interestingly, reduced brood size was statistically significant only in the last days of egg laying in two of these strains. This suggests the effect is due to early deterioration and aging of the transferred sperm. We detected a mild increase in embryonic lethality in only one of the strains, supporting the possibility that these lincRNAs do not affect fertility through critical roles in essential meiotic processes. Together our results indicate a sexually dimorphic outcome on fertility when lincRNA are removed and show that, unlike mammals, individual lincRNAs in C. elegans do play significant roles in male fertility.

Tongmai Zhuke decoction restrains the inflammatory reaction of macrophages for carotid artery atherosclerosis by up-regulating lincRNA-Cox2.

To explore the mechanism of Tongmai Zhuke decoction for promoting blood circulation by taking carotid artery atherosclerosis (CAA) as an example, two sets of in-depth transcriptomic data as well as two sets of single-cell RNA sequencing data related to the macrophages in CAA were included. STAR and DCC software were used to process in-depth transcriptomic data in order to measure the expression level of LncRNAs as well as mRNA according to FPKM analysis. Single-cell RNA sequencing data from Illumina NovaSeq 6000 were further analyzed by CellRanger channel, CellRanger count, Seurat R package, DoubletFinder package, CCA algorithm, LogNormalize, principal-component analysis, t-SNE and ToppGene online tools. Based On unsupervised clustering, a total of four diverse cell populations with distinct transcriptional features were found in human carotid atherosclerotic plaques. The macrophages were further annotated as the "effector cell" in the pathologic process of CAA, based on the expression of CD68+/CD440-. A total of 84 up-regulated genes and 58 down-regulated linc-RNAs were identified in samples with carotid atherosclerotic plaques. Thereinto, lincRNA-Cox2 is the most down-regulated LincRNA. For the macrophages in carotid atherosclerotic plaques, expression level of Il6, Ccl3, Ccl4 Il10 and Tnfa were significantly up-regulated, while Timp1 significantly down-regulated comparing with healthy carotid sample. The expression level of lincRNA-Cox2 was significantly increased in macrophages after treated by Tongmai Zhuke decoction, while Cxcl10, Ccl3, Ccl4, Cxcl2, Ccl5, and Ccl19 were significantly decreased. Collectively, Tongmai Zhuke decoction could restrain the inflammatory reaction of macrophages for carotid artery atherosclerosis by up-regulating lincRNA-Cox2.