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Objective To investigate the impacts of long non-coding RNA-lung adenocarcinoma metastasis- associated transcripton-1 (lncRNA MALAT1) on apoptosis, autophagy and phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt)/mammalian rapasin target protein (mTOR) pathway in granulosa cells of polycystic ovary syndrome (PCOS). Methods The expression levels of lncRNA MALAT1 in PCOS ovarian tissue, normal ovarian tissue, human ovarian granulosa cells (KGN) and normal ovarian epithelial cells IOSE80 were detected by qRT-PCR. KGN cells were cultured in vitro and grouped into the control group, the si-NC group, the si-MALAT1 group, the pc-NC group, the pc-MALAT1 group and the pc-MALAT1+740Y-P (PI3K activator) group. qRT-PCR was applied to detect the expression level of MALAT1 mRNA in cells of each transfection group. CCK-8 was applied to detect cell viability. Flow cytometry was applied to detect cell apoptosis rate. Transmission electron microscopy was applied to observe autophagosomes in KGN cells. Western blot assay was applied to detect expression levels of B-cell lymphoma 2 (Bcl-2), Bcl-2 associated X protein (Bax), microtubule- associated protein Ⅱ light chain 3 (LC3 Ⅱ), microtubule-associated protein Ⅰ light chain 3 (LC3 Ⅰ), Beclin1, p-PI3K, PI3K, p-Akt, Akt, p-mTOR and mTOR proteins in cells. Results The expression level of MALAT1 mRNA in PCOS ovarian tissue was lower than that in normal ovarian tissue, and that in KGN cells was lower than that in normal ovarian epithelial IOSE80 cells. A small number of autophagosomes were observed in KGN cells in the control group. After interfering MALAT1 expression, OD450 values (24, 48 and 72 hours) and the Bcl-2 protein expression of KGN cells were reduced, and the apoptosis rate, the expression of Bax, LC3 Ⅱ/LC3 Ⅰ, Beclin1, p-PI3K/PI3K, p-Akt/Akt and p-mTOR/ mTOR proteins were increased (P＜0.05). The number of autophagosomes increased. Changes of the above indexes were reversed after overexpression of MALAT1 (P＜0.05). Compared with the pc-MALAT1 group, the OD450 values (24, 48, 72 h), and the expression of Bcl-2 protein were obviously reduced in the pc-MALAT1+740Y-P group, while the apoptosis rate, number of autophagosomes, the expression of Bax, LC3 Ⅱ/LC3 Ⅰ, Beclin1, p-PI3K/PI3K, p-Akt/Akt, and p-mTOR/mTOR proteins were obviously increased (P＜0.05). The number of autophagosomes increased. Conclusion Overexpression of MALAT1 may inhibit apoptosis and autophagy in PCOS granulosa cells by inhibiting the PI3K/Akt/mTOR signaling pathway. [ABSTRACT FROM AUTHOR]

Objective To analyze the relationship between expression levels of long non-coding RNA (LncRNA) LINC00342 and microRNA-203a-3p (miR-203a-3p) in colorectal cancer tissue and the prognosis of patients within 5 years after surgery. Methods Samples of colorectal cancer tissue and paracancer tissue of 133 patients with colorectal cancer were collected. Expression levels of LncRNA LINC00342 and miR-203a-3p were detected by fluorescence quantitative PCR. Survival and death were recorded after 5 years of follow-up. The LncRNA LINC00342 and miR-203a-3p expressions and clinicopathological parameters in patients under different conditions were compared. The correlation between expressions of LncRNA LINC00342 and miR-203a-3p in colorectal cancer tissue was analyzed, and their predictive value for the prognosis was also analyzed. Results The expression level of LncRNA LINC00342 was higher in colorectal cancer tissue than that in paracancer tissue, and the expression level of miR-203a-3p was lower in colorectal cancer tissue than that in paracancer tissue (P＜0.05). The expression levels of LncRNA LINC00342 and miR-203a-3p in colorectal cancer tissue were negatively correlated (P＜0.05). The proportion of patients with low tumor differentiation, TNM stage Ⅲ and lymph node metastasis were higher in the LncRNA LINC00342 high expression group and the miR-203a-3p low expression group than those in the LncRNA LINC00342 low expression group and the miR-203a-3p high expression group, respectively (P＜ 0.05). The 5-year overall survival rate after operation was lower in the LncRNA LINC00342 high expression group and the miR-203a-3p low expression group (P＜0.05). The proportion of patients with low tumor differentiation, TNM stage Ⅲ, lymph node metastasis, and higher expression level of LncRNA LINC00342 were higher in colorectal cancer tissue of the death group than those in the survival group, and the expression level of miR-203a-3p was lower than that in the survival group (P＜0.05). Low tumor differentiation, TNM stage Ⅲ, lymph node metastasis, high expression of LncRNA LINC00342 and low expression of miR-203a-3p were independent risk factors for death within 5 years after colorectal cancer surgery (P＜0.05). The combined predictive value of LncRNA LINC00342 and miR-203a-3p for prognosis was greater than that of individual prediction. Conclusion LncRNA LINC00342 is higher expressed and miR-203a-3p is lower expressed in colorectal cancer tissue, and the combined detection of the two is expected to become a clinical evaluation indicator for predicting postoperative survival. [ABSTRACT FROM AUTHOR]

Objective To investigate the expression level of long non-coding RNA (lncRNA) AL365181.2 in cholangiocarcinoma (CHOL) and its effect on the functional characteristics of CHOL cells. Methods The Cancer Genome Atlas (TCGA) database was used to compare the expression level of lncRNA AL365181.2 between cancerous tissue and paracancerous tissue in CHOL patients, and the association between the expression level of lncRNA AL365181.2 and immune cell infiltration in CHOL tissue was analyzed. The Gene Set Enrichment Analysis (GSEA) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed for lncRNA AL365181.2. EdU assay, wound healing assay, Transwell assay, and xenograft tumor formation experiment were used to investigate the impact of lncRNA AL365181.2 on the proliferation, migration, invasion, and tumorigenic abilities of CHOL cells. Results The analysis of TCGA data showed that the expression level of lncRNA AL365181.2 in CHOL tissue was significantly higher than that in paracancerous tissue (Z=4.00,P

BACKGROUND: The relationship between heart failure (HF) and atrial fibrillation (AF) is clear, with up to half of patients with HF progressing to AF. The pathophysiological basis of AF in the context of HF is presumed to result from atrial remodeling. Upregulation of the transcription factor FOG2 (friend of GATA2; encoded by ZFPM2) is observed in human ventricles during HF and causes HF in mice. METHODS: FOG2 expression was assessed in human atria. The effect of adult-specific FOG2 overexpression in the mouse heart was evaluated by whole animal electrophysiology, in vivo organ electrophysiology, cellular electrophysiology, calcium flux, mouse genetic interactions, gene expression, and genomic function, including a novel approach for defining functional transcription factor interactions based on overlapping effects on enhancer noncoding transcription. RESULTS: FOG2 is significantly upregulated in the human atria during HF. Adult cardiomyocyte-specific FOG2 overexpression in mice caused primary spontaneous AF before the development of HF or atrial remodeling. FOG2 overexpression generated arrhythmia substrate and trigger in cardiomyocytes, including calcium cycling defects. We found that FOG2 repressed atrial gene expression promoted by TBX5. FOG2 bound a subset of GATA4 and TBX5 co-bound genomic locations, defining a shared atrial gene regulatory network. FOG2 repressed TBX5-dependent transcription from a subset of co-bound enhancers, including a conserved enhancer at the Atp2a2 locus. Atrial rhythm abnormalities in mice caused by Tbx5 haploinsufficiency were rescued by Zfpm2 haploinsufficiency. CONCLUSIONS: Transcriptional changes in the atria observed in human HF directly antagonize the atrial rhythm gene regulatory network, providing a genomic link between HF and AF risk independent of atrial remodeling. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is a common female reproductive endocrine disorder that is related with various factors including epigenetic and environment. Long non-coding RNA (lncRNA), with more than 200 nucleotides, are a kind of RNA molecules that do not code proteins. LncRNA can affect the expression of gene through epigenetic modification, transcriptional and post-transcriptional regulation. As a kind of competing endogenous RNA (ceRNA), lncRNA can affect the expression of target gene by competitively binding microRNA (miRNA). As a new regulatory mechanism, it can play an important role in many biological processes such as cell proliferation and differentiation, inflammatory response and immune response, which is closely related to many diseases. The ceRNA hypothesis also provides a further understanding of the mechanism of PCOS. Recently, the studies of lncRNA in PCOS significantly increased. The lncRNA differentially expressed in PCOS can involve as ceRNA in ovarian granulosa cell proliferation, oocyte maturation as well as hormone synthesis, and play an potential role in the development of PCOS. In this review, we summarize the roles of lncRNA as ceRNA in the occurrence and development of PCOS. [ABSTRACT FROM AUTHOR]

Dementia is the term used to describe a group of cognitive disorders characterized by a decline in memory, thinking, and reasoning abilities that interfere with daily life activities. Examples of dementia include Alzheimer's Disease (AD), Frontotemporal dementia (FTD), Amyotrophic lateral sclerosis (ALS), Vascular dementia (VaD) and Progressive supranuclear palsy (PSP). AD is the most common form of dementia. The hallmark pathology of AD includes formation of β-amyloid (Aβ) oligomers and tau hyperphosphorylation in the brain, which induces neuroinflammation, oxidative stress, synaptic dysfunction, and neuronal apoptosis. Emerging studies have associated long non-coding RNAs (lncRNAs) with the pathogenesis and progression of the neurodegenerative diseases. LncRNAs are defined as RNAs longer than 200 nucleotides that lack the ability to encode functional proteins. LncRNAs play crucial roles in numerous biological functions for their ability to interact with different molecules, such as proteins and microRNAs, and subsequently regulate the expression of their target genes at transcriptional and post-transcriptional levels. In this narrative review, we report the function and mechanisms of action of lncRNAs found to be deregulated in different types of dementia, with the focus on AD. Finally, we discuss the emerging role of lncRNAs as biomarkers of dementias. [ABSTRACT FROM AUTHOR]

Objective: Despite continuous progress in treatment, recurrence and metastasis limit further improvement in the prognosis of breast cancer (BC) patients. Our aim was to search for a crucial prognostic biomarker of BC. Materials and methods: Patient data were selected from The Cancer Genome Atlas (TCGA) and GTEx databases. Several online public databases, including Gene Expression Profiling Interactive Analysis (GEPIA), miRWalk, miRDB, and LncBase Predicted v.2, were used to identify potential upstream miRNAs and lncRNAs. These findings were validated through in vitro experiments. Results: A total of 1, 097 invasive BC samples and 572 normal breast tissues (including 113 samples from TCGA and 459 samples from GTEx) were collected for the study. CCT4 was not only significantly overexpressed in BC compared with normal breast tissues but also had important prognostic significance (P

Objective To study the application value of PET/CT radiomics combined with long noncoding RNA DiGeorge syndrome critical region gene 5 (LncRNA-DGCR5) in the precision medicine of non-small cell lung cancer (NSCLC). Methods A total of 106 NSCLC patients received PET/CT examination and chemoradiotherapy, and their efficacy was evaluated according to the Evaluation Criteria for Solid Tumor Efficacy after Treatment (RECIST). Patients with complete remission and partial remission were included in the response group (58 cases), and patients with stable or progressive disease were included in the non-response group (48 cases). Image texture parameters of PET/CT including SUVmax (maximum standard value), mean value, variance, kurtosis, skewness, contrast, entropy and energy were compared between groups. Real-time fluorescence quantitative PCR was used to detect LncRNA-DGCR5 expression in peripheral blood. Receiver operating characteristic curve (ROC) was constructed to analyze the predictive value of each index to the therapeutic efficacy of NSCLC patients. Results The SUVmax value, entropy and expression of LncRNA-DGCR5 were significantly lower in the response group than those in the non-response group (P＜0.05), and the energy was significantly higher in the response group than that in the non-response group (P＜0.05). There were no significant differences in the other parameters between the two groups. Patients were divided into the low LncRNA-DGCR5 expression group (51 cases) and the high LncRNA-DGCr5 expression group (55 cases) according to the mean expression of LncRNA-DGCR5 (2.01) as the critical value. Compared with the low LncRNA-DGCR5 expression group, the PET/CT image texture parameters of SUVmax and entropy were significantly increased in the high LncRNA-DGCR5 expression group, and the energy was significantly decreased (P＜0.05). ROC curve construction showed that the AUCs of SUVmax value, entropy, energy and LncRNA-DGCR5 expression on predicting the treatment efficacy of patients with NSCLC were 0.897, 0.851, 0.795 and 0.949 respectively, and the AUC of combined prediction was the highest at 0.998. Conclusion PET/CT radiomics combined with LncRNA-DGCR5 is helpful to predict the treatment efficacy of patients with NSCLC, thus providing the guidance for precision medicine of NSCLC. [ABSTRACT FROM AUTHOR]

Background Long non-coding RNAs (lncRNAs) have been illustrated to contribute to the development of gestational diabetes mellitus (GDM). In the present study, we aimed to elucidate how lncRNA taurine upregulated gene 1 (TUG1) influences insulin resistance (IR) in a high-fat diet (HFD)-induced mouse model of GDM. Methods We initially developed a mouse model of HFD-induced GDM, from which islet tissues were collected for RNA and protein extraction. Interactions among lncRNA TUG1/microRNA (miR)-328-3p/sterol regulatory element binding protein 2 (SREBP-2) were assessed by dual-luciferase reporter assay. Fasting blood glucose (FBG), fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR), HOMA pancreatic β-cell function (HOMA-β), insulin sensitivity index for oral glucose tolerance tests (ISOGTT) and insulinogenic index (IGI) levels in mouse serum were measured through conducting gain- and loss-of-function experiments. Results Abundant expression of miR-328 and deficient expression of lncRNA TUG1 and SREBP-2 were characterized in the islet tissues of mice with HFD-induced GDM. LncRNA TUG1 competitively bound to miR-328-3p, which specifically targeted SREBP-2. Either depletion of miR-328-3p or restoration of lncRNA TUG1 and SREBP-2 reduced the FBG, FINS, HOMA-β, and HOMA-IR levels while increasing ISOGTT and IGI levels, promoting the expression of the extracellular signal-regulated kinase (ERK) signaling pathway-related genes, and inhibiting apoptosis of islet cells in GDM mice. Upregulation miR-328-3p reversed the alleviative effects of SREBP-2 and lncRNA TUG1 on IR. Conclusion Our study provides evidence that the lncRNA TUG1 may prevent IR following GDM through competitively binding to miR-328-3p and promoting the SREBP-2-mediated ERK signaling pathway inactivation.

Background The present study investigated the regulatory effects of N6-methyladenosine (m6A) methyltransferase like-3 (METTL3) in diabetes-induced testicular damage. Methods In vivo diabetic mice and high glucose (HG) treated GC-1 spg cells were established. The mRNA and protein expressions were determined by real-time quantitative polymerase chain reaction, Western blot, immunofluorescence and immunohistochemistry staining. Levels of testosterone, blood glucose, cell viability, and apoptosis were detected by enzyme-linked immunosorbent assay, MTT, and flow cytometry, respectively. Molecular interactions were verified by RNA immunoprecipitation and RNA pull-down assay. Histopathological staining was performed to evaluate testicular injury. Results METTL3 and long non-coding RNA taurine up-regulated 1 (lncRNA TUG1) were downregulated in testicular tissues of diabetic mice and HG-treated GC-1 spg cells. METTL3 overexpression could reduce the blood glucose level, oxidative stress and testicular damage but enhance testosterone secretion in diabetic mouse model and HG-stimulated GC-1 spg cells. Mechanically, METTL3-mediated m6A methylation enhanced the stability of TUG1, then stabilizing the clusterin mRNA via recruiting serine and arginine rich splicing factor 1. Moreover, inhibition of TUG1/clusterin signaling markedly reversed the protective impacts of METTL3 overexpression on HG-stimulated GC-1 spg cells. Conclusion This study demonstrated that METTL3 ameliorated diabetes-induced testicular damage by upregulating the TUG1/clusterin signaling. These data further elucidate the potential regulatory mechanisms of m6A modification on diabetes-induced testicular injury.

Objective To investigate the expression of long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) in the epithelial-mesenchymal transition (EMT) model of human bronchial epithelial cell line 16HBE induced by human transforming growth factor-β1 (TGF-β1). Methods 16HBE cells were cultured in vitro, and the experiment established control group and treatment group. The cells in the treatment group were induced by TGF-β1 to establish an EMT cell model, and those in the control group were added with an equal volume of RPMI basic culture medium. At 24, 48, and 72 h after TGF-β1 treatment, an inverted microscope was used to observe cell morphology and distribution. At the time point when the cells in the treatment group began to show obvious spindle-shaped changes, the methods of RNA separation, reverse transcription, and quantitative real-time PCR were used to measure the relative expression levels of lncRNAs and miRNAs in the two groups. Results After 48 h of TGF-β1 treatment, the cells in the treatment group showed obvious spindle-shaped changes and an increase in intercellular space, suggesting that the EMT model was successfully established. At this time point, there were significant differences between the two groups in the relative expression levels of TBILA, NKILA, LNCRNA-ATB, HOTAIR, NEAT1, miR-125b-5p, miR-21-3p, miR-21-5p, miR-27a-3p, miR-27a-5p, miR-141-3p, miR-200c-3p, miR-17-5p, miR-34a-5p(t=-16.353-6.460,P

Background: Activation of vascular smooth muscle cell (VSMC) inflammation is vital to initiate vascular disease. The role of human-specific long noncoding RNAs in VSMC inflammation is poorly understood. Methods: Bulk RNA sequencing in differentiated human VSMCs revealed a novel human-specific long noncoding RNA called inflammatory MKL1 (megakaryoblastic leukemia 1) interacting long noncoding RNA (INKILN). INKILN expression was assessed in multiple in vitro and ex vivo models of VSMC phenotypic modulation as well as human atherosclerosis and abdominal aortic aneurysm. The transcriptional regulation of INKILN was verified through luciferase reporter and chromatin immunoprecipitation assays. Loss-of-function and gain-of-function studies and multiple RNA–protein and protein–protein interaction assays were used to uncover a mechanistic role of INKILN in the VSMC proinflammatory gene program. Bacterial artificial chromosome transgenic mice were used to study INKILN expression and function in ligation injury–induced neointimal formation. Results: INKILN expression is downregulated in contractile VSMCs and induced in human atherosclerosis and abdominal aortic aneurysm. INKILN is transcriptionally activated by the p65 pathway, partially through a predicted NF-κB (nuclear factor kappa B) site within its proximal promoter. INKILN activates proinflammatory gene expression in cultured human VSMCs and ex vivo cultured vessels. INKILN physically interacts with and stabilizes MKL1, a key activator of VSMC inflammation through the p65/NF-κB pathway. INKILN depletion blocks interleukin-1β–induced nuclear localization of both p65 and MKL1. Knockdown of INKILN abolishes the physical interaction between p65 and MKL1 and the luciferase activity of an NF-κB reporter. Furthermore, INKILN knockdown enhances MKL1 ubiquitination through reduced physical interaction with the deubiquitinating enzyme USP10 (ubiquitin-specific peptidase 10). INKILN is induced in injured carotid arteries and exacerbates ligation injury–induced neointimal formation in bacterial artificial chromosome transgenic mice. Conclusions: These findings elucidate an important pathway of VSMC inflammation involving an INKILN /MKL1/USP10 regulatory axis. Human bacterial artificial chromosome transgenic mice offer a novel and physiologically relevant approach for investigating human-specific long noncoding RNAs under vascular disease conditions. [ABSTRACT FROM AUTHOR]

Background/Aim. Prostate carcinoma (PCa) is second occurring carcinoma that affects the male population. Although PCa incidence rates are high, most cases have a favorable prognosis, with comfortable long-term life quality. The aim of the study was to compare long non-coding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5) plasma levels between healthy individuals and patients with PCa, and also between PCa patients with different prognostic scores. Methods. The present study included a total of 40 patients with PCa and a control group of 20 healthy individuals. PCa patients were divided into two subgroups (20 patients each) based on the prognostic criteria of the American Joint Committee on Cancer. The patient data were collected and analyzed; lncRNA GAS5 levels were quantified using the re-al-time polymerase chain reaction method. Statistical analysis was conducted using the IBM SPSS Statistics 26.0 computer program (IBM, USA, 2019). Results. The relative quantification of lncRNA GAS5 expression levels showed down-regulation in PCa patients compared to healthy individuals; however, the difference was marginally statistically significant (p = 0.056). With further analysis of the given results, we concluded that the expression level of lncRNA GAS5 was not significantly different in the first patient subgroup and the healthy individuals (p = 0.268). Patients from the second subgroup had significantly lower plasma levels of lncRNA GAS5 than healthy individuals (p = 0.033). The difference in the level of lncRNA GAS5 expression between patients with favorable prognoses (Group 1) and the ones with worse prognostic scores (Group 2) did not indicate statistical significance (p = 0.275). In both Group 1 (p = 0.805) and Group 2 (p = 0.454), the plasma levels of lncRNA GAS5 were not significantly different in comparison to the age (≤ 65 vs. > 65 years). Conclusion. One of the main objectives of PCa research is identifying novel and more efficient biomarkers. Conducted research provides strong evidence about the significance of lncRNAs GAS5 in PCa, as well as the correlation between decreased expression of lncRNA GAS5 and poor prognosis in various tumors.

Objective To explore the effect of thioridazine (TDZ) on proliferation and apoptosis of pancreatic cancer cells SW1990 and its regulatory effect on LINC00470. Methods Different concentrations of TDZ (5, 10 and 20 µmol/L) were used to treat human pancreatic cancer cells SW1990. si-NC and si-LINC00470 were transfected into SW1990 cells (the si-NC group and the si-LINC00470 group). After transfecting pcDNA and pcDNA-LINC00470 into SW1990 cells, TDZ were added to treat cells (the TDZ+pcDNA group and the TDZ+pcDNA-LINC00470 group). MTT, plate clone formation test were used to detect cell proliferation and clone formation ability. Flow cytometry was used to detect the apoptosis rate. The real-time fluorescent quantitative PCR was used to detect the expression level of LINC00470. Western blot assay was used to detect expression levels of activated aspartate specific cysteine protease (cleaved-caspase) 3 and cleaved-caspase9. Results Compared with the control group, the cell proliferation inhibition rate, apoptosis rate, cleaved-caspase3 and cleaved-caspase9 protein levels of SW1990 cells were increased, the number of cell clone formation was decreased, and the expression level of LINC00470 was decreased in the different dose TDZ groups (P＜0.05). Compared with the si-NC group, the cell proliferation inhibition rate, apoptosis rate, cleaved-caspase3 and cleaved-caspase9 protein levels of SW1990 cells were increased in the si-LINC00470 group, and the cell clone formation was reduced (P＜0.05). The transfection of pcDNALINC00470 could reverse the effect of TDZ on cell proliferation, apoptosis and colony formation of SW1990 cells. Conclusion TDZ can inhibit the proliferation, clone formation and induce apoptosis of pancreatic cancer cells by inhibiting the expression of LINC00470. [ABSTRACT FROM AUTHOR]

Objective To identify differentially expressed long non-coding RNAs（lncRNA） in testis of hyperuricemia-induced male infertility rats. Methods Hematoxylin-eosin（HE） staining was used to observe the histopathological morphology of rat testis. RNA was extracted from the testis of male SD rats in control group and hyperuricemia group and sequenced. Differentially expressed lncRNA were analyzed between two groups, and their target genes were predicted. GO and KEGG functional enrichment analysis were performed for differential lncRNA and target mRNA. Results Compared with those in the control group, 89 differentially expressed lncRNA（42 up-regulated and 47 down-regulated） and 50 differentially expressed mRNAs（29 up-regulated and 21 down-regulated） were identified in hyperuricemia group. GO enrichment analysis revealed that these differentially expressed lncRNA were mainly associated with the regulation of insulin receptor signaling pathway, the regulation of inflammatory response, developmental process and G-protein-coupled glutamate receptor binding. KEGG pathway enrichment analysis showed that differentially expressed lncRNA were mainly enriched in insulin signaling pathway, cGMP-PKG signaling pathway, cAMP signaling pathway and calcium signaling pathway. Conclusions The differential expression of lncRNA in testicular tissue of HUA rats may help elucidate the potential mechanism of lncRNA in hyperuricemia-induced reproductive disorders in male rats. [ABSTRACT FROM AUTHOR]

Objective To investigate the influence of N6-methyladenosine (m6A) recognition protein human antigen R (HuR) on the growth of colorectal cancer (CRC) by regulating long non-coding RNA T cell receptor gamma locus antisense RNA 1 (lncRNA TRG-AS1). Methods The content of m6A in cancer tissue, paracancer tissue and normal colon epithelial cells NCM460 and CRC cells HCT116, SW480 and LOVO were detected by colorimetric method. The expression of TRGAS1 was detected by real-time fluorescence quantitative PCR (qPCR). The expression of HuR protein was detected by Western blot assay. HCT116 cells were divided into the Ct group, the OE-NC group, the OE-HuR group, the si-NC group, the si-HuR group, the si-HuR + pcDNA group and the si-HuR+ pcDNA-TRG-AS1 group. CCK-8 assay was applied to detect cell proliferation. Plate cloning assay was used to detect the ability of cells to form clones. Flow cytometry was applied to detect apoptosis. Scratch-healing assay was applied to detect cell migration. Transwell assay was used to detect cell invasion. In vivo tumor xenograft experiment was used to observe tumor growth in nude mice. Methylated RNA immunoprecipitation (MeRIP) was applied to detect the presence of m6A sites on TRG-AS1. RNA co-immunoprecipitation (RIP) and RNA pull-down experiments were used to demonstrate the interaction of TRG-AS1 with HuR protein. Results In CRC tissue and cells, HuR protein and TRG-AS1 were highly expressed, and m6A content was decreased. In HCT116 cells, the expression levels of HuR protein and TRG-AS1 were the highest, and the m6A content was the lowest (P＜0.05), therefore, HCT116 cells were selected as the research object. Compared with the si-NC group, the expression levels of HuR protein and TRG-AS1 decreased in the si-HuR group, and the m6A content increased (P＜0.05). Compared with the OENC group, expression levels of HuR protein and TRG-AS1 increased in the OE-HuR group, and the m6A content decreased (P＜0.05). Compared with the si-HuR group and the si-HuR+pcDNA group, there were no significant differences in changes of HuR protein and m6A content in the si-HuR+pcDNA-TRG-AS1 group, but the expression of TRG-AS1 increased (P＜0.05). The down-regulation of HuR could inhibit HCT116 cell proliferation, migration, invasion and growth of transplanted tumor in vivo, and promote cell apoptosis, while up-regulation of HuR showed the opposite trends. The overexpression of TRG-AS1 attenuated the inhibitory effect of silencing HuR on HCT116 cell proliferation, migration, invasion, in vivo xenograft growth, and the promotion of apoptosis. There was m6A site on TRG-AS1, and TRG-AS1 could interact with HuR protein. Conclusion Silencing the m6A recognition protein HuR can inhibit the proliferation, migration, invasion of HCT116 cells and promote cell apoptosis by inhibiting the expression of TRG-AS1. [ABSTRACT FROM AUTHOR]

Objective To investigate the influence of long non-coding RNA (lncRNA) OPA-interacting protein 5 antisense transcript 1 (OIP5-AS1) on the proliferation, apoptosis, migration and invasion of glioma cells. Methods Tissue specimens from 33 glioma patients (14 low-grade gliomas and 19 high-grade gliomas) and 33 patients with craniocerebral injury were collected. Real-time quantitative PCR (qPCR) was used to detect the mRNA expression levels of OIP5-AS1, microRNA-942-5p (miR-942-5p) and checkpoint kinase 1 (CHEK1) in tissue samples and cells, and analyze the correlation between OIP5-AS1, miR-942-5p and CHEK1 mRNA expression level in glioma tissues. Human glioma cell lines U87, SHG-44, U251 and H4 and normal human astrocytes NHA were cultured in vitro. The expression of CHEK1 protein in cells were detected by Western blot assay. U87 cells were divided into the control (NC) group, the siRNA negative control (si-NC) group, the OIP5-AS1 siRNA (si-OIP5-AS1) group, the si-OIP5-AS1+inhibitor negative control (si-OIP5- AS1+anti-NC) group and the si-OIP5-AS1+miR-942-5p inhibitor (si-OIP5-AS1+anti-miR-942-5p) group. Cells were transfected with Lipofectamine 3000 reagent. After transfection, the expression levels of OIP5-AS1, miR-942-5p and CHEK1 mRNA and protein in cells were detected by qPCR and Western blot assay. MTT assay was used to detect the cell proliferation activity. Flow cytometry was used to detect cell apoptosis. Transwell assay was used to detect cell migration and invasion abilities. Finally, the interaction of OIP5-AS1 and miR-942-5p and CHEK1 and miR-942-5p were verified by dual luciferase and RNA immunoprecipitation (RIP) experiments. Results OIP5-AS1 and CHEK1 were overexpressed in glioma tissue and cells, while miR-942-5p was underexpressed (all P＜0.05). Correlation analysis showed that OIP5-AS1 was negatively correlated with miR-942-5p, and miR-942-5p and CHEK1 mRNA was negatively correlated in glioma tissue. The expression level of CHEK1 mRNA was positively correlated with OIP5-AS1. The expression levels of OIP5-AS1 and CHEK1 mRNA were significantly higher in high-grade glioma tissue than those in low-grade glioma tissue, while the expression level of miR-942-5p was significantly lower in high-grade glioma tissue than that in low-grade glioma tissue (P＜0.01). Silencing OIP5-AS1 significantly up-regulated miR-942-5p and inhibited the mRNA and protein expression of CHEK1 (P＜0.05). Silencing OIP5-AS1 significantly inhibited the proliferation, migration and invasion of U87 cells, promoting apoptosis of U87 cells (P＜0.05). Down-regulation of miR-942-5p could up-regulate the expression of CHEK1 and block the effects of OIP5-AS1 silencing on glioma cell proliferation, migration, invasion and apoptosis (P＜0.05). Dualluciferase and RIP experiments confirmed that miR-942-5p was a target of OIP5-AS1, and CHEK1 was a downstream target gene of miR-942-5p. Conclusion Silencing OIP5-AS1 may inhibit the expression of CHEK1 by up-regulating miR-942- 5p, inhibit the invasion and migration of glioma cells, and promote cell apoptosis. [ABSTRACT FROM AUTHOR]

Cholangiocarcinoma is a highly malignant tumor with a poor prognosis, limited treatment options, and complicated pathogenesis. Competitive endogenous RNA is a kind of transcripts that can competitively bind miRNA, including long non - coding RNA and circular RNA. Competitive endogenous RN A is known to be involved in a variety of tumors. It can modulate the occurrence and development of cholangiocarcinoma by regulating the biological behavior, cell metabolism, inflammatory process and epithelial - mesenchymal transition of cholangiocarcinoma cells. Here we review recent research progress on the role of long non - coding RNA and circular RNA in cholangiocarcinoma to help better understand the pathogenesis of cholangiocarcinoma. [ABSTRACT FROM AUTHOR]

Objective: To investigate the expression of long non-coding RNA nucleolar small molecule host gene 12 (LncRNA SNHG12) in prostate cancer and its influences on cell proliferation and invasion for its clinical application in the diagnosis and treatment of prostate cancer. Methods: Cancer tissue samples and their adjacent tissue samples collected from 125 patients with prostate cancer in our hospital from March 2017 to March 2019, and human normal prostate epithelial cells RWPE-1, as well as human prostate cancer cells DU145, PC3, LNCaP were set as the research objects. qRT-PCR was used to detect the expression level of LncRNA SNHG12 in prostate cancer tissues and prostate cancer cells. Cell transfection technology was applied to transfect the LncRNA SNHG12 knockdown plasmid (si-SNHG12) and its negative control (si-NC) into PC3 cells; CCK-8 method was used to measure cell proliferation ability in each group; Transwell assay was used to analyze the invasion ability of PC3 cells in each group; Western blotting was used to detect the expression levels of invasion associated protein MMP9 and epithelial-mesenchymal transition (EMT) marker proteins E-cadherin, N-cadherin and Vimentin in PC3 cells of each group. Results: The expression level of LncRNA SNHG12 in prostate cancer tissue was significantly higher than that in adjacent tissues (P<0.05). Compared with that in RWPE-1 cells, the expression level of LncRNA SNHG12 in prostate cancer cell lines DU145, PC3, and LNCaP was obviously increased (P<0.05), and its highest expression was found in PC3 cells, thus, PC3 cells were selected for subsequent experiments. knockdown of SNHG12 significantly inhibited the proliferation and invasion of PC3 cells, and suppressed the expressions of MMP9, N-cadherin and Vimentin proteins, simultaneously upregulated the expression of E-cadherin protein (P<0.05). Conclusion: LncRNA SNHG12 is highly expressed in prostate cancer tissues and cells. Knockdown of SNHG12 expression can inhibit proliferation, invasion and EMT occurrence of PC3 cells. [ABSTRACT FROM AUTHOR]

Background: Abnormalities in Ca2+ homeostasis are associated with cardiac arrhythmias and heart failure. Triadin plays an important role in Ca2+ homeostasis in cardiomyocytes. Alternative splicing of a single triadin gene produces multiple triadin isoforms. The cardiac-predominant isoform, mouse MT-1 or human Trisk32, is encoded by triadin exons 1 to 8. In humans, mutations in the triadin gene that lead to a reduction in Trisk32 levels in the heart can cause cardiac dysfunction and arrhythmias. Decreased levels of Trisk32 in the heart are also common in patients with heart failure. However, mechanisms that maintain triadin isoform composition in the heart remain elusive.Methods: We analyzed triadin expression in heart explants from patients with heart failure and cardiac arrhythmias and in hearts from mice carrying a knockout allele for Trdn-as, a cardiomyocyte-specific long noncoding RNA encoded by the antisense strand of the triadin gene, between exons 9 and 11. Catecholamine challenge with isoproterenol was performed on Trdn-as knockout mice to assess the role of Trdn-as in cardiac arrhythmogenesis, as assessed by ECG. Ca2+ transients in adult mouse cardiomyocytes were measured with the IonOptix platform or the GCaMP system. Biochemistry assays, single-molecule fluorescence in situ hybridization, subcellular localization imaging, RNA sequencing, and molecular rescue assays were used to investigate the mechanisms by which Trdn-as regulates cardiac function and triadin levels in the heart.Results: We report that Trdn-as maintains cardiac function, at least in part, by regulating alternative splicing of the triadin gene. Knockout of Trdn-as in mice downregulates cardiac triadin, impairs Ca2+ handling, and causes premature death. Trdn-as knockout mice are susceptible to cardiac arrhythmias in response to catecholamine challenge. Normalization of cardiac triadin levels in Trdn-as knockout cardiomyocytes is sufficient to restore Ca2+ handling. Last, Trdn-as colocalizes and interacts with serine/arginine splicing factors in cardiomyocyte nuclei and is essential for efficient recruitment of splicing factors to triadin precursor mRNA.Conclusions: These findings reveal regulation of alternative splicing as a novel mechanism by which a long noncoding RNA controls cardiac function. This study indicates potential therapeutics for heart disease by targeting the long noncoding RNA or pathways regulating alternative splicing. [ABSTRACT FROM AUTHOR]

Liquid chromatography-mass spectrometry (LC-MS) is an effective tool for high-throughput quantification of oligonucleotides that is crucial for understanding their biological roles and developing diagnostic tests. This paper presents a high-throughput LC-MS/MS method that may be versatilely applied for a wide range of oligonucleotides, making it a valuable tool for rapid screening and discovery. The method is demonstrated using an in-house synthesized MALAT-1 Antisense oligonucleotide (ASO) as a test case. Biological samples were purified using a reversed liquid-liquid extraction process automated by a liquid handling workstation and analyzed with ion-pairing LC-MS/MS. The assay was evaluated for sensitivity (LLOQ = 2 nM), specificity, precision, accuracy, recovery, matrix effect, and stability in rat cerebrospinal fluid (CSF) and plasma. Besides some existing considerations such as column selection, ion-pairing reagent, and sample purification, our work focused on the following four subtopics: 1) selecting the appropriate Multiple Reaction Monitoring (MRM) transition to maximize sensitivity for trace-level ASO in biological samples; 2) utilizing a generic risk-free internal standard (tenofovir) to avoid crosstalk interference from the oligo internal standard commonly utilized in the LC-MS assay; 3) automating the sample preparation process to increase precision and throughput; and 4) comparing liquid-liquid extraction (LLE) and solid-phase extraction (SPE) as sample purification methods in oligo method development. The study quantified the concentration of MALAT-1 ASO in rat CSF and plasma after intrathecal injection and used the difference between the two matrices to evaluate the injection technique. The results provide a solid foundation for further internal oligonucleotide discovery and development., (© 2024. Merck & Co., Inc., Rahway, NJ, USA and its affiliates, under exclusive licence to American Association of Pharmaceutical Scientists.)

Background: Pulmonary hypertension is a devastating vascular disorder characterized by extensive pulmonary vascular remodeling, ultimately leading to right ventricular failure and death. Activation of PDGF (platelet-derived growth factor) signaling promotes the hyperproliferation of pulmonary arterial smooth muscle cells (PASMCs), thus contributing to the pulmonary vascular remodeling. However, the molecular mechanisms that govern hyperproliferation of PASMCs induced by PDGF remain largely unknown, including the contribution of long noncoding RNAs (lncRNAs). In this study, we aimed to identify a novel lncRNA regulated by PDGF implicated in PASMC proliferation in pulmonary vascular remodeling., Methods: RNA-sequencing analysis was conducted to identify a novel lncRNA named vessel-enriched lncRNA regulated by PDGF-BB (VELRP). Functional investigations of VELRP were performed using knockdown and overexpression strategies along with RNA sequencing. Validation of the function and potential mechanisms of VELRP were performed through Western blot, RNA immunoprecipitation, and chromatin immunoprecipitation assays., Results: We identified a novel vessel-enriched lncRNA with an increased response to PDGF-BB stimulus. VELRP was identified as an evolutionarily conserved RNA molecules. Modulation of VELRP in PASMCs significantly altered cell proliferation. Mechanistically, VELRP enhances trimethylation of H3K4 by interacting with WDR5 (WD repeat-containing protein 5), leading to increased expression of CDK (cyclin-dependent kinase) 1, CDK2, and CDK4 and consequent hyperproliferation of PASMCs. The pathological relevance of VELRP upregulation in pulmonary artery was confirmed using rat pulmonary hypertension models in vivo, as well as in PASMCs from patients with idiopathic pulmonary arterial hypertension patients. Specific knockdown of VELRP in smooth muscle cells using adeno-associated virus type 9 SM22α (smooth muscle protein 22α) promoter-shRNA-mediated silencing of VELRP resulted in a significant decrease in right ventricular systolic pressure and vascular remodeling in rat pulmonary hypertension model., Conclusions: VELRP, as an lncRNA upregulated by PDGF-BB, mediates PASMC proliferation via WDR5/CDK signaling. In vivo studies demonstrate that targeted intervention of VELRP in smooth muscle cells can prevent the development of pulmonary hypertension.

Background: Activation of the immune system contributes to cardiovascular diseases. The role of human-specific long noncoding RNAs in cardioimmunology is poorly understood., Methods: Single-cell sequencing in peripheral blood mononuclear cells revealed a novel human-specific long noncoding RNA called HEAT4 (heart failure-associated transcript 4). HEAT4 expression was assessed in several in vitro and ex vivo models of immune cell activation, as well as in the blood of patients with heart failure (HF), acute myocardial infarction, or cardiogenic shock. The transcriptional regulation of HEAT4 was verified through cytokine treatment and single-cell sequencing. Loss-of-function and gain-of-function studies and multiple RNA-protein interaction assays uncovered a mechanistic role of HEAT4 in the monocyte anti-inflammatory gene program. HEAT4 expression and function was characterized in a vascular injury model in NOD.CB17-Prkdc scid/Rj mice., Results: HEAT4 expression was increased in the blood of patients with HF, acute myocardial infarction, or cardiogenic shock. HEAT4 levels distinguished patients with HF from people without HF and predicted all-cause mortality in a cohort of patients with HF over 7 years of follow-up. Monocytes, particularly anti-inflammatory CD16 + monocytes, which are increased in patients with HF, are the primary source of HEAT4 expression in the blood. HEAT4 is transcriptionally activated by treatment with anti-inflammatory interleukin-10. HEAT4 activates anti-inflammatory and inhibits proinflammatory gene expression. Increased HEAT4 levels result in a shift toward more CD16 + monocytes. HEAT4 binds to S100A9, causing a monocyte subtype switch, thereby reducing inflammation. As a result, HEAT4 improves endothelial barrier integrity during inflammation and promotes vascular healing after injury in mice., Conclusions: These results characterize a novel endogenous anti-inflammatory pathway that involves the conversion of monocyte subtypes into anti-inflammatory CD16 + monocytes. The data identify a novel function for the class of long noncoding RNAs by preventing protein secretion and suggest long noncoding RNAs as potential targets for interventions in the field of cardioimmunology., Competing Interests: None.

Mir483 is a conserved and highly expressed microRNA in placental mammals, embedded within the Igf2 gene. Its expression is dysregulated in a number of human diseases, including metabolic disorders and certain cancers. Here, we investigate the developmental regulation and function of Mir483 in vivo. We find that Mir483 expression is dependent on Igf2 transcription and the regulation of the Igf2/H19 imprinting control region. Transgenic Mir483 overexpression in utero causes fetal, but not placental, growth restriction through insulin-like growth factor 1 (IGF1) and IGF2 and also causes cardiovascular defects leading to fetal death. Overexpression of Mir483 post-natally results in growth stunting through IGF1 repression, increased hepatic lipid production, and excessive adiposity. IGF1 infusion rescues the post-natal growth restriction. Our findings provide insights into the function of Mir483 as a growth suppressor and metabolic regulator and suggest that it evolved within the INS-IGF2-H19 transcriptional region to limit excessive tissue growth through repression of IGF signaling., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: To analyse the relative expression and diagnostic potential of lncRNA XIST (XIST) in peri-implantitis, and explore the related mechanism of XIST in peri-implantitis., Materials and Methods: XIST expression in saliva of patients with peri-implantitis was detected by qRT-PCR. The diagnostic significance of XIST in peri-implantitis was assessed by ROC curve. Clinical indicators of the included patients were collected and the correlation between XIST levels and peri-implant indicators was determined by Pearson correlation analysis. Bioinformatic prediction and luciferase reporter assay confirmed the targeting relationship of XIST with downstream factors., Results: Salivary XIST levels were obviously higher in patients with peri-implantitis than in the healthy control group, and the AUC value for identifying patients was 0.8742 with a sensitivity and specificity of 83.5% and 81.4%. Patients in the peri-implantitis group had higher levels of plaque index (PLI), sulcus bleeding index (SBI) and probing depth (PD) than those in the healthy control group, and the expression of XIST was positively correlated with PLI, SBI, and PD levels. In addition, miR-150-5p was confirmed to be a potential downstream target of XIST., Conclusion: XIST was overexpressed in the saliva of patients with peri-implantitis and correlated with the severity of the disease. XIST has high diagnostic significance for detecting peri-implantitis.

Activated B-cell-like diffuse large B-cell lymphoma (ABC-DLBCL) is an aggressive lymphoma characterized by constitutive NF-κB activation, but whether miR-17∼92 contributes to this activation remains unclear. Herein, we sought to evaluate the role of miR-17∼92 in the process of NF-κB activation in ABC-DLBCL. We found that the expression of miR-17∼92 primary transcript was positively correlated with NF-κB activity, miR-17∼92 activated the NF-κB signaling in ABC-DLBCL, and its over-expression promoted ABC-DLBCL cell growth, accelerated cell G1 to S phase transition and enhanced cell resistance to NF-κB inhibitor. Importantly, miR-17∼92 promoted NF-κB activation through directly targeting multiple ubiquitin-editing regulators to lead to increase the K63-linked polyubiquitination and decrease the K48-linked polyubiquitination of RIP1 complex in ABC-DLBCL. We further found that miR-17∼92 selectively activated IκB-α and NF-κB p65 but not NF-κB p52/p100, and high miR-17∼92 expression was also associated with poorer outcome in ABC-DLBCL patients. Overall, our results showed that miR-17∼92 selectively activated the canonical NF-κB signaling via targeting ubiquitin-editing regulators to lead to constitutively NF-κB activation and poorer outcome in ABC-DLBCL. These findings uncovered an innovative function of miR-17∼92 and previously unappreciated regulatory mechanism of NF-κB activation in ABC-DLBCL. Targeting miR-17∼92 may thus provide a novel bio-therapeutic strategy for ABC-DLBCL patients., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Abstract Background Glioma is one of the most malignant brain tumors, accounting for about half of the gliomas that occur in central nervous system (CNS), originates from the glial tissue of the brain. The aim of the present study was to determine the expression levels of 5 lncRNAs (MDC1-AS1, HOXA11-AS, MALAT1, CASC2, ADAMTS9-AS2) in patients with high-grade glioma in comparison with low grade glioma. Methods This was a retrospective study which determined molecular biomarker on pathologic glioma samples. We examined 100 patients’ pathologic block which consisted of 50 pathology samples of high-grade glioma (case group) and control group consisted of 50 pathology samples of low-grade glioma. This research was performed using real time polymerase chain reaction (PCR) technique. Results The results showed that the expression of ADAMTS9-AS2 and HOXA11-AS genes significantly increased with increasing tumor grade. Also the expression of CASC2 gene significantly decreased with increasing tumor grade. Conclusions It was concluded that ADAMTS9-AS2 and HOXA11-AS and CASC2 are promising lncRNA markers in prognosis of glioma.

Background: Identifying the factors affecting osteoblast differentiation of periodontal ligament cells (PDLCs) can help enhance the regeneration of periodontal tissue. LncRNA plasmacytoma variant translocation 1 (lncPVT1) is an important regulatory factor involved in many biological processes, but its role in osteogenesis remains unclear.Methods: Expressions of osteogenic markers were detected by quantitative reverse transcription polymerase chain reaction and Western blot analysis. Alkaline phosphatase staining was conducted for early osteoblast differentiation and alizarin red S staining was used for mineral deposition. RNA sequencing was used to identify the miRNAs regulated by lncPVT1 during osteogenesis. Cell transfection was used to overexpress or knockdown lncPVT1 and miR-10a-5p. Dual luciferase reporter assays were conducted to analyze the binding of miR-10a-5p to brain-derived neurotrophic factor (BDNF).Results: LncPVT1 was significantly increased during osteogenic induction of PDLCs. Overexpression of lncPVT1 promoted osteogenesis, whereas lncPVT1 knockdown inhibited this process. RNA sequencing showed that miR-10a-5p expression was significantly increased after lncPVT1 knockdown. RNA immunoprecipitation assay further demonstrated the binding potential of lncPVT1 and miR-10a-5p. MiR-10a-5p inhibited the osteogenesis of PDLCs, and partially reversed the stimulatory effects of lncPVT1. Subsequently, we identified a predicted binding site for miR-10a-5p on BDNF and confirmed it using dual luciferase reporter assays. Moreover, lncPVT1 upregulated the expression of BDNF, whereas miR-10a-5p downregulated BDNF expression. BDNF promoted osteogenesis and partially rescued the si-lncPVT1-mediated inhibition of PDLCs osteogenic differentiation.Conclusions: LncPVT1 positively regulated the osteogenic differentiation of PDLCs via miR-10a-5p and BDNF. Our results provide a promising target for enhancing the osteogenic potential of PDLCs. [ABSTRACT FROM AUTHOR]

BACKGROUND: Long non-coding RNA (lncRNA) AFAP1-AS1 is associated with tumorigenesis and poor prognosis of various cancers. However, the expression, function and underlining mechanism of lncRNA AFAP1-AS1 in colon cancer is poorly characterized at present. METHODS: We investigated the expression level and prognosis implication of lncRNA AFAP1-AS1 in colon cancer. Then we used siRNAs to inhibit the expression of AFAP1-AS1 in colon cancer cell lines to investigate its function in colon cancer. Finally, we explored the underlining mechanisms for the biological functions of AFAP1-AS1 in colon cancer. RESULTS: We found that AFAP1-AS1 was up-regulated and associated with poor survival of colon cancer. Inhibition of AFAP1-AS1 significantly suppressed colon cancer cell proliferation and metastasis in vitro and in vivo. Moreover, AFAP1-AS1 promoted the progression of colon cancer partly through activation of the Wnt/β-catenin signaling pathway. CONCLUSIONS: Our study demonstrated that lncRNA AFAP1-AS1 was up-regulated and associated with poor survival of colon cancer. Inhibition of AFAP1-AS1 significantly suppressed colon cancer progression via Wnt/β-catenin signaling pathway. AFAP1-AS1 could be a prognostic biomarker and therapeutic target for colon cancer. [ABSTRACT FROM AUTHOR]

Objective To explore the mechanism of long non-coding RNA (LncRNA) zinc finger antisense 1 (ZFAS1) targeting microRNA (miR)-373 to induce cisplatin (DDP) resistance in hepatoma cells. Methods There were the normal culture group, the si-NC group and the si-ZFAS1 group in this study. The levels of ZFAS1 and miR-373 were detected by real-time quantitative PCR (qPCR). The cells were treated with DDP (0, 50, 100, 200 and 300 μmol/L) for 12 h on the basis of the si-NC group and the si-ZFAS1 group. CCK-8 was used to detect cell proliferation. Transwell was used to detect cell invasion. Western blot assay was used to detect the protein levels of matrix metalloproteinase (MMP)2 and MMP9. Double luciferase was used to verify the targeting relationship between ZFAS1 and miR-373. Inhibitor miR-373 was added on the basis of the si-ZFAS1 group, and the expression levels of MMP2 and MMP9 were detected. Results The expression level of ZFAS1 was lower in the si-ZFAS1 group than that of the normal culture group and the si-NC group, and the expression level of miR-373 was higher than that of the normal culture group and the si-NC group (P＜0.05). After treatment with different concentrations of cisplatin, the cell proliferation rate, invasion number and the expression levels of invasion proteins MMP2 and MMP9 basically showed a decreasing trend in the si-NC group and the si-ZFAS1 group. The above indexes were lower in the si-ZFAS1 group than their corresponding concentrations of the si-NC group (P＜0.05). Starbase analysis showed that miR-373 and ZFAS1 had complementary binding sites, which were verified by double luciferase. The expression levels of MMP2 and MMP9 proteins were higher in the si-ZFAS1+inhibitor miR-373 group than those in the si-ZFAS1 group and the si-ZFAS1+inhibitor NC group (P＜0.05). Conclusion ZFAS1 may reduce DDP resistance in liver cancer cells, and the mechanism may be related to the regulation of miR-373. [ABSTRACT FROM AUTHOR]

Objective To investigate the effect of LincRNA-P21 on the migration and invasion of triple negative breast cancer (TNBC) cells by targeting miR-17-3p. Methods qPCR was used to detect the expression levels of LincRNA-P21 and miR-17-3p in tumor tissues, normal adjacent tissues and 6 kinds of breast cells (normal breast cells MCF-10A, breast cancer cells MDA-MB-231, MDA-MB-435, MDA-MB-468, BT549 and T47D). MDA-MB-231 cells were taken. LincRNA-P21 was overexpressed alone (the control group, the pcDNA3.1 blank group and the pcDNA - LincRNA-P21 group), miR-17-3p expression was inhibited (the control group, the miR-17-3p blank group and the miR-17-3p inhibitor group), and overexpression LincRNA-P21+ inhibited miR-17-3p (the control group, the miR-17-3p inhibitor group and the pcDNA-LincRNA-P21+miR-17-3p inhibitor group). The proliferation of MDA-MB-231 cells was detected by CCK-8 assay. The number of colonies was detected by colony formation assay. The migration ability was detected by cell scratch assay, and the invasion ability was detected by Transwell assay. The protein expressions of E-cadherin and Vimentin were detected by Western blot assay. Results The expression of LincRNA-P21 was significantly lower in TNBC than that in adjacent tissues (0.48±0.03 vs. 1.03±0.06, t=11.714, P＜0.01). The expression of miR-17-3p was significantly higher in TNBC than that in adjacent tissues (2.93±0.17 vs. 1.02±0.04, t=15.593, P＜0.01). The expression levels of LincRNA-P21 mRNA in different breast cancer cell lines were significantly lower than that in MCF-10A (P＜0.01). The expressions of miR-17-3p mRNA in different breast cancer cell lines were significantly higher than that in MCF-10A (P＜0.01). The overexpression of LincRNA-P21 inhibited cell proliferation, colony formation and invasion (P＜0.01). The inhibition of miR17-3p expression could reduce cell proliferation, colony formation and invasion (P＜0.01). Compared with the miR-NC group, the overexpression of LincRNA-P21 and inhibition of miR-17-3p could significantly reduce cell proliferation, colony formation and invasion (P＜0.01), increase the expression of E-cadherin and inhibit the expression of vimentin (P＜0.01). Conclusion LincRNA-P21 can reduce miR-17-3p expression and inhibit MDA-MB-231 cell proliferation, colony formation, migration and invasion through competitive binding. [ABSTRACT FROM AUTHOR]

Objective To investigate the effect of long non coding RNA (LncRNA) PVT1 on allergic rhinitis (AR) and its related mechanism. Methods A total of 24 BALB/c mice were used in this study, of which 6 mice were in the normal group, and the remaining 18 mice were treated with ovalbumin (OVA) and Al (OH)3 to establish the AR model. Eighteen mice were randomly divided into the model group, the AR+NC group (empty vector lentivirus injected via tail vein) and the AR+shPVT1 group (shPVT1 lentivirus injected via tail vein). The behavioral score was used to investigate allergic symptoms of the mice in each group. HE staining was used to analyze the pathological changes of nasal mucosa in mice. qPCR was used to detect LncRNA PVT1, miR-149-5p and chitinase-3-like protein 1 (CHI3L1) relative mRNA expression. The protein expression of CHI3L1 was detected by Western blot assay. The serum levels of IgE, IL-5 and TNF-α were analyzed by ELISA. Luciferase reporter vector of LncRNA PVT1 and CHI3L1 of wild type (WT) and mutant type (MT) were constructed and transfected into 293T cells with miR-149-5p mimic. The relative luciferase activity was analyzed by double luciferase assay. Results Compared with the model group, the behavior score was significantly decreased，serum levesls of IgE, IL-5 and TNF- α were reduced, the relative mRNA or protein expression of LncRNA PVT1 and CHI3L1 were significantly decreased, the relative mRNA of miR-149-5p was increased and the inflammatory response of the nasal mucosa was reduced in the AR+shPVT1 group. Dual luciferase assay confirmed that LncRNA PVT1 up-regulated the expression of miR 149-5p target gene CHI3L1 through competitive binding miR-149-5p. Conclusion LncRNA PVT1, which is abnormally highly expressed in AR model mice, can inhibit the expression of miR-149-5p and enhance the expression of CHI3L1 by exerting its ceRNA function, thus promote inflammatory symptoms of nasal mucosa tissue and allergic reactions in mice. [ABSTRACT FROM AUTHOR]

Objective To explore the mechanism of long non-coding RNA (LncRNA) growth arrest-specific 5 (GAS5) targeting microRNA (miR) -103 to reduce 3T3L1 adipocyte insulin resistance (IR). Methods The 3T3L1 mouse preadipocytes were cultured and induced to differentiation, and oil red O staining was used to identify cell differentiation. The 3T3L1 adipocyte IR model was established. Cells were divided into the control group, the model group, the empty vector group (transfected with pEGFP-C1 empty vector), the GAS5 over-expression group (transfected with pEGFP-C1-GAS5 vector), the GAS5 over-expression + mimic NC group (transfected with pEGFP-C1-GAS5+mimic NC) and the GAS5 overexpression+miR-103 mimic group (transfected with pEGFP-C1-GAS5+miR-103 mimic). Real-time fluorescent quantitative PCR was used to detect the levels of GAS5 mRNA and miR-103 in cells. liquid scintillation method was used to detect glucose uptake capacity. Western blot assay was used to detect the expression levels of insulin receptor substrate-1 (IRS-1), p-IRS-1, peroxisome proliferator-activated receptor γ (PPARγ), glucose transporter 4 (GLUT4), and protein kinase B (AKT) and p-AKT proteins. Dual luciferase was used to identify the targeting sites of miR-103 and GAS5. Results After induction, the cells were round, the cell body enlarged, the cytoplasm was rich and contained a large number of lipid droplets. The oil red staining was obvious, showing‘finger-ring-like’structure. The model was successfully constructed. Compared with the control group, the GAS5 mRNA level, glucose uptake capacity, p-IRS-1/IRS-1, PPARγ, GLUT4 and p)AKT/AKT protein levels decreased in the model group, the empty vector group and the GAS5 over-expression+miR-103 mimic group (P＜0.05), the miR-103 mRNA level in cells increased (P＜0.05). Compared with the model group and the empty vector group, the GAS5 mRNA level, glucose uptake capacity, p-IRS-1/IRS-1, PPARγ, GLUT4 and p-AKT/AKT protein levels increased in the GAS5 over-expression group and the GAS5 over-expression+mimic NC group (P＜0.05), while the miR-103 mRNA level in cells decreased (P＜0.05). Compared with the GAS5 over-expression group and the GAS5 over-expression + mimic NC group, the GAS5 mRNA level, glucose uptake capacity, p-IRS-1/IRS-1, PPARγ, GLUT4 and p-AKT/AKT protein levels decreased in the GAS5 over-expression + miR-103 mimic group (P＜0.05), the miR-103 mRNA level increased (P＜0.05). The complementary binding sites of MiR-103 and GAS5 were verified by the dual luciferase targeting relationship. Conclusion Targeted down-regulation of miR-103 expression after over-expression of GAS5 can reduce IR of 3T3L1 adipocytes. [ABSTRACT FROM AUTHOR]

The mineralization capability of cementoblasts is the foundation for repairing orthodontic treatment‐induced root resorption. It is essential to investigate the regulatory mechanism of mineralization in cementoblasts under mechanical compression to improve orthodontic therapy. Autophagy has a protective role in maintaining cell homeostasis under environmental stress and was reported to be involved in the mineralization process. Long noncoding RNAs are important regulators of biological processes, but their functions in compressed cementoblasts during orthodontic tooth movement remain unclear. In this study, we showed that compressive force downregulated the expression of mineralization‐related markers. LincRNA‐p21 was strongly enhanced by compressive force. Overexpression of lincRNA‐p21 downregulated the expression of mineralization‐related markers, while knockdown of lincRNA‐p21 reversed the compressive force‐induced decrease in mineralization. Furthermore, we found that autophagy was impeded in compressed cementoblasts. Then, overexpression of lincRNA‐p21 decreased autophagic activity, while knockdown of lincRNA‐p21 reversed the autophagic process decreased by mechanical compression. However, the autophagy inhibitor 3‐methyladenine abolished the lincRNA‐p21 knockdown‐promoted mineralization, and the autophagy activator rapamycin rescued the mineralization inhibited by lincRNA‐p21 overexpression. Mechanistically, the direct binding between lincRNA‐p21 and FoxO3 blocked the expression of autophagy‐related genes. In a mouse orthodontic tooth movement model, knockdown of lincRNA‐p21 rescued the impeded autophagic process in cementoblasts, enhanced cementogenesis, and alleviated orthodontic force‐induced root resorption. Overall, compressive force‐induced lincRNA‐p21 inhibits the mineralization capability of cementoblasts by impeding the autophagic process. [ABSTRACT FROM AUTHOR]

Objective To screen and clarify the mechanism of long non-coding RNA CD48-AS (lncRNA CD48-AS) and the antisense complementary molecule CD48 in the process of N-3-oxododecanoyl-L-homoserine lactone (3-O-C12- HSL) hampering the maturation of human monocyte-induced dendritic cells (Mo-DCs). Methods Mo-DCs were extracted from the peripheral blood of healthy individuals, and the immature Mo-DCs were divided into three groups for lncRNA chip analysis: the negative control group (0.1% DMSO), the lipopolysaccharide (LPS) positive control group (100 μg/L LPS) and the treatment group (100 μg/L LPS+40 μmol/L 3-O-C12-HSL). The natural antisense lncRNA expressed more than 5 times in the lncRNA expression profile were screened for Cluster analysis. The natural antisense lncRNA CD48-AS was screened. Immature Mo-DCs were divided into the negative control group, the LPS positive control group, and the 3-O-C12-HSL treatment group (5, 10, 25 μmol/L 3-O-C12-HSL). The expression of lncRNA CD48-AS and antisense molecule CD48 were measured using quantitative PCR in each group. The complementary regions of lncRNA CD48-AS and CD48 and the protein coding function of lncRNA CD48-AS were analyzed through bioinformatics. Whether lncRNA CD48-AS affected the expression of CD48 by forming a dimer with CD48 was verified through the ribonuclease protection experiment (RPA). Preliminary experiments were carried out on the localization of lncRNA CD48-AS in cells. Results The lncRNA expression profile of Mo-DCs showed specific changes after 3-O-C12-HSL treatment. 3-O-C12-HSL down-regulated the expression of lncRNA CD48-AS and its antisense target molecule CD48 induced by LPS. Bioinformatics analysis showed that lncRNA CD48-AS was a non-coding RNA without protein coding function. lncRNA CD48-AS may form RNA dimers with CD48 to reduce the degradation of CD48 by RNase and increase the expression of CD48. lncRNA CD48-AS was mainly located in the nucleus in Mo-DCs, with less expression in cytoplasm. Conclusion 3-O-C12-HSL can inhibit the maturation of Mo-DCs by down-regulating lncRNA CD48-AS and then affecting the expression of CD48. [ABSTRACT FROM AUTHOR]

Background: Cardiac hypertrophy is an adaptive response to pressure overload aimed at maintaining cardiac function. However, prolonged hypertrophy significantly increases the risk of maladaptive cardiac remodeling and heart failure. Recent studies have implicated long noncoding RNAs in cardiac hypertrophy and cardiomyopathy, but their significance and mechanism(s) of action are not well understood., Methods: We measured lincRNA-p21 RNA and H3K27ac levels in the hearts of dilated cardiomyopathy patients. We assessed the functional role of lincRNA-p21 in basal and surgical pressure-overload conditions using loss-of-function mice. Genome-wide transcriptome analysis revealed dysregulated genes and pathways. We labeled proteins in proximity to full-length lincRNA-p21 using a novel BioID2-based system. We immunoprecipitated lincRNA-p21-interacting proteins and performed cell fractionation, ChIP-seq (chromatin immunoprecipitation followed by sequencing), and co-immunoprecipitation to investigate molecular interactions and underlying mechanisms. We used GapmeR antisense oligonucleotides to evaluate the therapeutic potential of lincRNA-p21 inhibition in cardiac hypertrophy and associated heart failure., Results: lincRNA-p21 was induced in mice and humans with cardiomyopathy. Global and cardiac-specific lincRNA-p21 knockout significantly suppressed pressure overload-induced ventricular wall thickening, stress marker elevation, and deterioration of cardiac function. Genome-wide transcriptome analysis and transcriptional network analysis revealed that lincRNA-p21 acts in trans to stimulate the NFAT/MEF2 (nuclear factor of activated T cells/myocyte enhancer factor-2) pathway. Mechanistically, lincRNA-p21 is bound to the scaffold protein KAP1 (KRAB-associated protein-1). lincRNA-p21 cardiac-specific knockout suppressed stress-induced nuclear accumulation of KAP1, and KAP1 knockdown attenuated cardiac hypertrophy and NFAT activation. KAP1 positively regulates pathological hypertrophy by physically interacting with NFATC4 to promote the overactive status of NFAT/MEF2 signaling. GapmeR antisense oligonucleotide depletion of lincRNA-p21 similarly inhibited cardiac hypertrophy and adverse remodeling, highlighting the therapeutic potential of inhibiting lincRNA-p21 ., Conclusions: These findings advance our understanding of the functional significance of stress-induced long noncoding RNA in cardiac hypertrophy and demonstrate the potential of lincRNA-p21 as a novel therapeutic target for cardiac hypertrophy and subsequent heart failure., Competing Interests: None.

Objective: To investigate whether long non-coding RNA (lncRNA) Gm8097 (LncGm8097) is associated with male infertility., Methods: The expression and bilogical role of LncGm8097 were investigated., Results: LncGm8097 expression was down-regulated in the testis tissues with moderate and severe hypospermatogenesis compared with those with normal spermatogenesis and mild hypospermatogenesis (p<0.05). LncGm8097 down-regulation significantly promoted apoptosis and inhibited proliferation in GC1 and GC2 cells. In addition, LncGm8097 was significantly down-regulated in mouse model of hypospermatogenesis and correlated with cell apoptosis and proliferation. LncGm8097 was located immediately upstream of PRPS2, and correlated with Bcl-2/P53/caspase 6/caspase 9 signal pathway., Conclusion: LncGm8097 down-regulation correlates with hypospermatogenesis, which may offer new insights into the pathogenesis of male infertility.

Background: Breast cancer, particularly the estrogen receptor positive (ER+) subtype, remains a leading cause of cancer-related death among women. Endocrine therapy is the most effective treatment for ER+ breast cancer; however, the development of resistance presents a significant challenge. This study explored the role of the breast cancer antiestrogen resistance 4 (BCAR4) gene as a potential driver of resistance and a pivotal biomarker in breast cancer., Patients and Methods: The researchers undertook a comprehensive analysis of 1743 patients spanning 6 independent cohorts. They examined the association of BCAR4 expression with patient outcomes across all breast cancer types and the PAM50 molecular subtypes. The relationship between elevated BCAR4 expression and resistance to endocrine therapy including AIs, the prevailing standard-of-care for endocrine therapy, was also investigated., Results: This meta-analysis corroborated the link between BCAR4 expression and adverse outcomes as well as resistance to endocrine therapy in breast cancer. Notably, BCAR4 expression is clinically significant in luminal A and B subtypes. Additionally, an association between BCAR4 expression and resistance to AI treatment was discerned., Conclusion: This study expands on previous findings by demonstrating that BCAR4 expression is associated with resistance to newer therapies. The identification of patients with intrinsic resistance to hormone therapy is crucial to avoid ineffective treatment strategies. These findings contribute to our understanding of endocrine therapy resistance in breast cancer and could potentially guide the development of more effective treatment strategies., Competing Interests: Disclosure The authors have stated that they have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Rationale: Cartilage-hair hypoplasia (CHH, OMIM # 250250) is a rare autosomal recessive disorder, which includes cartilage-hair hypoplasia-anauxetic dysplasia (CHH-AD) spectrum disorders. CHH-AD is caused by homozygous or compound heterozygous mutations in the RNA component of the mitochondrial RNA-processing Endoribonuclease (RMRP) gene., Patient Concerns: Here, we report 2 cases of Korean children with CHH-AD., Diagnoses: In the first case, the patient had metaphyseal dysplasia without hypotrichosis, diagnosed by whole exome sequencing (WES), and exhibited only skeletal dysplasia and lacked extraskeletal manifestations, such as hair hypoplasia and immunodeficiency. In the second case, the patient had skeletal dysplasia, hair hypoplasia, and immunodeficiency, which were identified by WES., Interventions: The second case is the first CHH reported in Korea. The patients in both cases received regular immune and lung function checkups., Outcomes: Our cases suggest that children with extremely short stature from birth, with or without extraskeletal manifestations, should include CHH-AD as a differential diagnosis., Lessons Subsections: Clinical suspicion is the most important and RMRP sequencing should be considered for the diagnosis of CHH-AD., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Fragile X-associated primary ovarian insufficiency (FXPOI), characterized by amenorrhea before age 40 years, occurs in 20% of female FMR1 premutation carriers. Presently, there are no molecular or biomarkers that can help predicting which FMR1 premutation women will develop FXPOI. We previously demonstrated that high FMR4 levels can discriminate between FMR1 premutation carriers with and without FXPOI. In the present study the relationship between the expression levels of FMR4 and the ovarian reserve markers was assessed in female FMR1 premutation carriers under age of 35 years., Methods: We examined the association between FMR4 transcript levels and the measures of total antral follicle count (AFC) and serum anti-müllerian hormone (AMH) levels as markers of ovarian follicle reserve., Results: Results revealed a negative association between FMR4 levels and AMH (r = 0.45) and AFC (r = 0.64). Statistically significant higher FMR4 transcript levels were found among those FMR1 premutation women with both, low AFCs and AMH levels., Conclusions: These findings reinforce previous studies supporting the association between high levels of FMR4 and the risk of developing FXPOI in FMR1 premutation carriers., (© 2024. The Author(s).)

Background: Ovarian cancer is a fatal gynecologic malignancy. Long non-coding RNA (lncRNA) has been verified to serve as key regulator in ovarian cancer tumorigenesis., Objective: The aim of the study was to study the functions and mechanism of lncRNA PITPNA-AS1 in ovarian cancer cellular process., Methods: Clinical ovarian cancer samples were collected and stored at an academic medical center. Cellular fractionation assays and fluorescence in situ hybridization were conducted to locate PITPNA-AS1 in OC cells. TUNEL staining, colony-forming assays, and Transwell assays were performed for evaluating cell apoptosis as well as proliferative and migratory abilities. Western blot was conducted for quantifying protein levels of epithelialmesenchymal transition markers. The binding relation between genes was verified by RNA pulldown, RNA immunoprecipitation, and luciferase reporter assays. Gene expression levels in ovarian cancer tissues and cells were subjected to RT-qPCR., Results: PITPNA-AS1 level was downregulated in ovarian cancer samples and cells. PITPNA-AS1 overexpression contributed to the accelerated ovarian cancer cell apoptosis and inhibited cell migration, proliferation, and epithelial-mesenchymal transition process. In addition, PITPNA-AS1 interacted with miR-223-3p to regulate RHOB. RHOB knockdown partially counteracted the repressive impact of PITPNA-AS1 on ovarian cancer cell activities., Conclusion: PITPNA-AS1 inhibited ovarian cancer cellular behaviors by targeting miR-223-3p and regulating RHOB.

It is already possible to capture and measure RNA-RNA interactions with high-throughput technologies such as RNA in situ conformation sequencing.[15] RNA in situ conformation sequencing captures RNA-RNA interactions by crosslinking RNA molecules that are in physical proximity to each other. Mechanistically, they demonstrate that I Trdn-as i interacts with the I Trdn i pre-mRNA and with the sarcoplasmic reticulum splicing factors serine/arginine-rich splicing factors 1 and 10. Keywords: Editorials; RNA, long noncoding; RNA splicing EN Editorials RNA, long noncoding RNA splicing 715 717 3 08/30/22 20220830 NES 220830 We increasingly recognize that noncoding RNAs provide a vast and multifaceted regulatory landscape in the heart. [Extracted from the article]

Background: Glioma is one of the most malignant brain tumors, accounting for about half of the gliomas that occur in central nervous system (CNS), originates from the glial tissue of the brain. The aim of the present study was to determine the expression levels of 5 lncRNAs (MDC1-AS1, HOXA11-AS, MALAT1, CASC2, ADAMTS9-AS2) in patients with high-grade glioma in comparison with low grade glioma. Methods: This was a retrospective study which determined molecular biomarker on pathologic glioma samples. We examined 100 patients' pathologic block which consisted of 50 pathology samples of high-grade glioma (case group) and control group consisted of 50 pathology samples of low-grade glioma. This research was performed using real time polymerase chain reaction (PCR) technique. Results: The results showed that the expression of ADAMTS9-AS2 and HOXA11-AS genes significantly increased with increasing tumor grade. Also the expression of CASC2 gene significantly decreased with increasing tumor grade. Conclusions: It was concluded that ADAMTS9-AS2 and HOXA11-AS and CASC2 are promising lncRNA markers in prognosis of glioma. [ABSTRACT FROM AUTHOR]

Objective: To explore the expression relationship and significance of long chain non-coding RNA nuclear-enriched abundant transcript 1 (LncRNA NEAT1) and miR-27a-3p in serum and cerebrospinal fluid of patients with Alzheimer disease (AD)., Methods: Sixty-six AD patients received by the department of neurology of our hospital from October 2019 to September 2021 were gathered, according to the clinical dementia rating scale score, they were grouped into mild group (≤1 point, n =41) and moderate-to-severe group (>1 point, n =25). Another 66 cases of serum and cerebrospinal fluid samples from outpatient physical examination personnel were regarded as the control group. The general information on all subjects was recorded and cognition was assessed; real-time quantitative PCR was performed to measure the expression levels of miR-27a-3p and NEAT1 in serum and cerebrospinal fluid; enzyme-linked immunosorbent assay was performed to measure the protein levels of β-amyloid precursor protein cleaving enzyme 1 (BACE1), β-amyloid (Aβ) 40 and Aβ42 in cerebrospinal fluid; Spearman' s method was performed to analyze the correlation of serum miR-27a-3p and NEAT1 levels with mini-mental state examination (MMSE) and montreal cognitive assessment (MoCA) scores; Pearson method was performed to analyze the correlation between serum miR-27a-3p and NEAT1 levels and Aβ deposition standard uptake value ratio (SUVR) and cerebrospinal fluid miR-27a-3p, NEAT1, BACE1, Aβ42 and Aβ40 levels., Results: The MMSE score [21 (17, 25), 9(7, 11) vs . 27 (21, 34)], MoCA score [17 (12, 21), 10 (7, 13) vs . 27 (21, 31)], serum miR-27a-3p level (0.55±0.13, 0.46±0.06 vs . 0.97±0.22), cerebrospinal fluid miR-27a-3p (0.48±0.10, 0.35±0.10 vs . 1.03±0.31), Aβ42 levels [(303.55±36.77) ng/L, (231.45±34.14) ng/L vs . (499.99±53.63) ng/L] and Aβ42/Aβ40 ratio (0.030±0.008, 0.022±0.007 vs . 0.048±0.010) of AD patients in mild group and moderate-to-severe group were all lower than those in the control group, and the moderate-to-severe group were lower than the mild group (all P < 0.05); the serum NEAT1 level (2.31±0.64, 3.13±0.76 vs . 1.05±0.20), SUVR (1.50±0.29, 1.76±0.52 vs . 0.74±0.15), and cerebrospinal fluid NEAT1 (3.51±1.24, 4.30±1.65 vs . 1.01±0.23) and BACE1 levels [(55.78±5.98) μg/L, (72.32±16.08) μg/L vs . (21.39±3.73) μg/L] were higher than those in the control group, and the moderate-to-severe group were higher than the mild group (all P < 0.05). Serum NEAT1 level in AD patients was positively correlated with SUVR, cerebrospinal fluid NEAT1 and BACE1 ( r =0.350, 0.606, 0.341, P < 0.05), and negatively correlated with MMSE score and MoCA score ( r =-0.473, -0.482, all P < 0.05); serum miR-27a-3p level was positively correlated with cerebrospinal fluid miR-27a-3p level, MMSE score and MoCA score ( r =0.695, 0.424, 0.412, all P < 0.05), and negatively correlated with SUVR and cerebrospinal fluid BACE1 level ( r =-0.521, -0.447, all P < 0.05)., Conclusion: The expression trends of NEAT1 and miR-27a-3p in the serum and cerebrospinal fluid of AD patients are consistent, the level of NEAT1 is increased, and the level of miR-27a-3p is decreased. The levels of the two are negatively correlated, which is related to the degree of Aβ deposition in the brain of AD patients and is involved in the progression of AD.

Background: Necroptosis-related long noncoding RNAs (lncRNAs) play crucial roles in cancer initiation and progression. Nevertheless, the role and mechanism of necroptosis-related lncRNAs in soft tissue sarcomas (STS) is so far unknown and needs to be explored further., Methods: Clinical and genomic data were obtained from the UCSC Xena database. All STS patients' subclusters were performed by unsupervised consensus clustering method based on the prognosis-specific lncRNAs, and then assessed their survival advantage and immune infiltrates. In addition, we explored the pathways and biological processes in subclusters through gene set enrichment analysis. At last, we established the necroptosis-related lncRNA-based risk signature (NRLncSig) using the least absolute shrinkage and selection operator (LASSO) method, and explored the prediction performance and immune microenvironment of this signature in STS., Results: A total of 911 normal soft tissue samples and 259 STS patients were included in current study. 39 prognosis-specific necroptosis-related lncRNAs were selected. Cluster 2 had a worse survival than the cluster 1 and characterized by different immune landscape in STS. A worse outcome in the high-risk group was observed by survival analysis and indicated an immunosuppressive microenvironment. The ROC curve analyses illustrated that the NRLncSig performing competitively in prediction of prognosis for STS patients. In addition, the nomogram presents excellent performance in predicting prognosis, which may be more beneficial towards STS patients' treatment., Conclusions: Our result indicated that the NRLncSig could be a good independent predictor of prognosis, and significantly connected with immune microenvironment, thereby providing new insights into the roles of necroptosis-related lncRNAs in STS., (© 2024. The Author(s).)