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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]

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]

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: 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]

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]

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]

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]

Objective To explore the protective effect of astragalus polysaccharide on chronic renal failure in mice and its potential molecular mechanism. Methods The chronic renal failure mouse model was established by 5/6 nephrectomy in male Balb/c mice. They were randomly divided into the model group and astragalus polysaccharide intervention group (APS group) with 10 mice in each group. Another sham operation group was set up. After normal feeding for 7 weeks, the APS group was given astragalus polysaccharide 100 mg/(kg·d) gavage, and the remaining groups were given an equal volume of normal saline. Samples of stool, urine, blood, kidney and colon tissues were collected after 4 weeks. The creatinine (Scr), urea nitrogen (BUN) and 24 h urine protein were determined. After the tissues were fixed and embedded, the tissues were stained with HE and Sirius red for pathological analysis. Western blot assay and immunohistochemical staining were used to detect the tight junction protein-1 family (Claudin-1, Occludin-1, ZO-1) and p-NF- κB expression level. The enzymelinked immunosorbent assay (ELISA) was used to detect the serum interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF- α) concentration. The real-time fluorescent quantitative PCR was used to detect long-chain non compiled RNA (lncRNA) Arid2-IR, IL-1β, IL-6 and TNF-α expression changes and changes in the fecal flora of mice. Results The blood Scr, BUN and 24 h urine protein were significantly decreased in the APS group than those of the model group. HE staining showed that the pathological damage of kidney and colon tissues were improved in the APS group compared with those of the model group. Sirius red staining showed that the degree of fibrosis was significantly improved in the APS group. Western blot assay and immunohistochemical staining showed that the expression of tight junction protein-1 family in colonic tissues was increased and the expression of p-NF- κB protein in renal tissues was decreased in the APS group compared with the model group. ELISA results showed that the levels of serum IL-1β, IL-6 and TNF-α were significantly decreased in the APS group compared with those of the model group. The relative expression levels of lncRNA Arid2-IR, IL1β, IL-6 and TNF-α were significantly decreased in the APS group compared with those of the model group. The expression levels of lactic acid bacillus and bifidobacterium were higher in the APS group than those of the model group, while the relative expression level of E. coli decreased. Conclusion Astragalus polysaccharide may regulate the intestinal flora of mice by regulating the lncRNA Arid2-IR/NF-κB signal axis, thereby repairing the intestinal barrier damage, maintaining the normal intestinal physiological environment and improving chronic renal failure. [ABSTRACT FROM AUTHOR]

Background: Exercise can induce physiological myocardial hypertrophy (PMH), and former athletes can live 5 to 6 years longer than nonathletic controls, suggesting a benefit after regression of PMH. We previously reported that regression of pathological myocardial hypertrophy has antihypertrophic effects. Accordingly, we hypothesized that antihypertrophic memory exists even after PMH has regressed, increasing myocardial resistance to subsequent pathological hypertrophic stress.Methods: C57BL/6 mice were submitted to 21 days of swimming training to develop PMH. After termination of exercise, PMH regressed within 1 week. PMH regression mice (exercise hypertrophic preconditioning [EHP] group) and sedentary mice (control group) then underwent transverse aortic constriction or a sham operation for 4 weeks. Cardiac remodeling and function were evaluated with echocardiography, invasive left ventricular hemodynamic measurement, and histological analysis. LncRNA sequencing, chromatin immunoprecipitation assay, and comprehensive identification of RNA-binding proteins by mass spectrometry and Western blot were used to investigate the role of Mhrt779 involved in the antihypertrophic effect induced by EHP.Results: At 1 and 4 weeks after transverse aortic constriction, the EHP group showed less increase in myocardial hypertrophy and lower expression of the Nppa and Myh7 genes than the sedentary group. At 4 weeks after transverse aortic constriction, EHP mice had less pulmonary congestion, smaller left ventricular dimensions and end-diastolic pressure, and a larger left ventricular ejection fraction and maximum pressure change rate than sedentary mice. Quantitative polymerase chain reaction revealed that the long noncoding myosin heavy chain-associated RNA transcript Mhrt779 was one of the markedly upregulated lncRNAs in the EHP group. Silencing of Mhrt779 attenuated the antihypertrophic effect of EHP in mice with transverse aortic constriction and in cultured cardiomyocytes treated with angiotensin II, and overexpression enhanced the antihypertrophic effect. Using chromatin immunoprecipitation assay and quantitative polymerase chain reaction, we found that EHP increased histone 3 trimethylation (H3K4me3 and H3K36me3) at the a4 promoter of Mhrt779. Comprehensive identification of RNA-binding proteins by mass spectrometry and Western blot showed that Mhrt779 can bind SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4 (Brg1) to inhibit the activation of the histone deacetylase 2 (Hdac2)/phosphorylated serine/threonine kinase (Akt)/phosphorylated glycogen synthase kinase 3β(p-GSK3β) pathway induced by pressure overload.Conclusions: Myocardial hypertrophy preconditioning evoked by exercise increases resistance to pathological stress via an antihypertrophic effect mediated by a signal pathway of Mhrt779/Brg1/Hdac2/p-Akt/p-GSK3β. [ABSTRACT FROM AUTHOR]

To investigate the role of Linc00891 in osteosarcoma (OS) and its mechanism. Methods The expressions of Linc00891 in different OS cell lines U-2 OS, Saos-2, MG-63, SW 1353 and human osteoblast cell line hFOB 1.19 were detected by qPCR. Saos-2 and MG-63 OS cell lines were transfected with Linc00891 vector. CCK-8 method, plate cloning method and Transwell chamber were used to detect the effects of Linc00891 overexpression on the proliferation, colony forming ability and migration ability. Western blot assay was used to detect the expressions of E-cadherin (E-cad) and N-cadherin (N-cad) related to epithelial-mesenchymal transition. RNA pulldown assay was used to detect the binding relationship between Linc00891 and miR-27a-3p in OS cells. TCF/LEF Reporter Kit was used to detect the effects of overexpression of Linc00891 and up-regulation of miR-27a-3p on Wnt/β-catenin signaling pathway in different OS cell lines. Results The expression levels of Linc00891 in different OS cell lines U-2 OS, Saos-2, MG-63 and SW 1353 were significantly lower than those in normal osteoblast cell line hFOB 1.19 (P＜0.05). The overexpression of Linc00891 could inhibit the proliferation, clone formation, migration and epithelial mesenchymal transition of human OS cell lines Saos-2 and MG-63 (P＜0.05). There was a binding relationship between Linc00891 and miR-27a-3p in OS cells. The overexpression of Linc00891 could reverse the activation of miR-27a-3p on Wnt/β -catenin signaling pathway (P＜0.05). Conclusion Linc00891 plays an anti-tumor role in OS by competitively binding and inhibiting miR-27a-3p. [ABSTRACT FROM AUTHOR]

Pre-eclampsia is one of the categories of hypertensive disorder complicating pregnancy, but its etiology and pathogenesis have not been clearly studied. Pre-eclampsia is a multi-factor, multi-mechanism and multi-pathway disease. At present, the main pathogenesis theories include insufficient recasting of uterine spiral arterioles, immune imbalance, oxidative stress, genetic factors and so on. Abnormal biological function of trophoblasts (proliferation, migration, invasion and apoptosis) may play a major role in the occurrence and development of pre-eclampsia, which will seriously affect maternal and infant health. Studies have shown that lncRNA was previously regarded as "transcriptional noise" with no biological function. However, with the rapid development of high-throughput sequencing technology and genome sequencing technology in recent years, it has been found that lncRNA can regulate the expression of various functions in the body. For example, lncRNA is abnormally expressed in the placenta of pre-eclampsia, which regulates the proliferation, migration, invasion and apoptosis of trophoblast cells through different target genes and signal pathways, thus leading to pre -eclampsia. Therefore, exploring the lncRNA associated with pre-eclampsia may provide a new way to understand the pathogenesis of pre-eclampsia and to identify new therapeutic targets. This review focuses on the regulation of trophoblast biology by abnormal expression of lncRNA in pre-eclampsia. [ABSTRACT FROM AUTHOR]

Ovarian cancer is one of the common gynecological malignancies. Because the early symptoms are not obvious in the course of its development, diagnosis is often in the advanced stage. Most patients have a poor prognosis and a high mortality rate. There is still a lack of reliable diagnostic markers and other diagnostic methods for early detection and screening. Therefore, it is of great significance to find biomarkers with better specificity and sensitivity for improving the prognosis of ovarian cancer patients. In recent years, the in-depth study of traditional tumor markers and the discovery of non-coding RNA have brought a breakthrough to the early diagnosis of ovarian cancer. Combined detection of serum tumor markers can improve the sensitivity and specificity of early diagnosis of ovarian cancer, which has great clinical significance. Non-coding RNA plays an important role in the occurrence and development of ovarian cancer, providing evidence for the search for new biomarkers of ovarian cancer. Biomarkers with potential for diagnosis and prediction of ovarian cancer are reviewed to provide help for early clinical diagnosis of ovarian cancer and further improve the quality of life of patients. [ABSTRACT FROM AUTHOR]

The incidence of gynecological malignant tumor is increasing year by year, and the key to improve its prognosis is early diagnosis and early treatment. In the future development of medicine, the diagnosis and treatment of diseases will be located at the level of gene. At present, the research on the regulation mechanism of non-coding RNA on cell phenotype is gradually unfolding. Since the abnormal expression of long non-coding RNA (lncRNA) colon cancer associated transcription 1 (CCAT1) in colorectal cancer was found in 2012, its regulatory role in a variety of other malignant tumors has been studied in succession. At present, studies on the mechanism of lncRNA mainly focus on the interactions between lncRNA and miRNA, and lncRNA is associated with the occurrence and development of malignant tumors through the tumorigenic effect of the downstream effectors regulated by miRNA. This paper reviews the mechanism of CCAT1 in gynecological cancer, and analyze research status and future development. [ABSTRACT FROM AUTHOR]

Cervical cancer is the second largest female malignant tumor after breast cancer. The main pathogenic factor of cervical cancer is human papillomavirus (HPV) infection. The incidence and mortality of cervical cancer have been decreased thanks to the use of HPV vaccine and advances in surgery and chemoradiotherapy. However, metastasis, recurrence and drug resistance are still great challenges in clinical therapeutics. Long-stranded non-coding RNA (lncRNA) is longer than 200 nt, most of which can not encode proteins, and only a few of which are translated into peptides. LncRNAs such as H19 and HOTAIR have been proved to play an important role in the initiation and progression of cervical cancer, and are closely related to the abnormal activation of PI3K/Akt, Wnt and other signaling pathways. LncRNA involved in the development of cervical cancer and its signal pathways are reviewed to explore potential biomarkers for diagnosis or prediction of prognosis, or effective targets for gene therapy. [ABSTRACT FROM AUTHOR]

BACKGROUND: The angiogenic function of endothelial cells is regulated by numerous mechanisms, but the impact of long noncoding RNAs (lncRNAs) has hardly been studied. We set out to identify novel and functionally important endothelial lncRNAs. METHODS: Epigenetically controlled lncRNAs in human umbilical vein endothelial cells were searched by exon-array analysis after knockdown of the histone demethylase JARID1B. Molecular mechanisms were investigated by RNA pulldown and immunoprecipitation, mass spectrometry, microarray, several knockdown approaches, CRISPR-Cas9, assay for transposase-accessible chromatin sequencing, and chromatin immunoprecipitation in human umbilical vein endothelial cells. Patient samples from lung and tumors were studied for MANTIS expression. RESULTS: A search for epigenetically controlled endothelial lncRNAs yielded lncRNA n342419, here termed MANTIS, as the most strongly regulated lncRNA. Controlled by the histone demethylase JARID1B, MANTIS was downregulated in patients with idiopathic pulmonary arterial hypertension and in rats treated with monocrotaline, whereas it was upregulated in carotid arteries of Macaca fascicularis subjected to atherosclerosis regression diet, and in endothelial cells isolated from human glioblastoma patients. CRISPR/Cas9-mediated deletion or silencing of MANTIS with small interfering RNAs or GapmeRs inhibited angiogenic sprouting and alignment of endothelial cells in response to shear stress. Mechanistically, the nuclear-localized MANTIS lncRNA interacted with BRG1, the catalytic subunit of the switch/sucrose nonfermentable chromatin-remodeling complex. This interaction was required for nucleosome remodeling by keeping the ATPase function of BRG1 active. Thereby, the transcription of key endothelial genes such as SOX18, SMAD6, and COUP-TFII was regulated by ensuring efficient RNA polymerase II machinery binding. CONCLUSION: MANTIS is a differentially regulated novel lncRNA facilitating endothelial angiogenic function. [ABSTRACT FROM AUTHOR]

Background: Calcific aortic valve disease is characterized by an abnormal mineralization of the aortic valve. Osteogenic activity in the aortic valve is under the control of NOTCH1, which regulates the expression of key pro-osteogenic genes such as RUNX2 and BMP2. Long noncoding RNAs (lncRNAs) may reprogram cells by altering the gene expression pattern.Methods: Multidimensional genomic profiling was performed in human aortic valves to document the expression of lncRNAs and the DNA methylation pattern in calcific aortic valve disease. In-depth functional assays were carried out to document the impact of lncRNA on the mineralization of the aortic valve.Results: We documented that lncRNA H19 (H19) was increased in calcific aortic valve disease. Hypomethylation of the promoter region was observed in mineralized aortic valves and was inversely associated with H19 expression. Knockdown and overexpression experiments showed that H19 induces a strong osteogenic phenotype by altering the NOTCH1 pathway. Gene promoter analyses showed that H19 silenced NOTCH1 by preventing the recruitment of p53 to its promoter. A knockdown of H19 in valve interstitial cells (VICs) increased the expression of NOTCH1 and decreased the level of RUNX2 and BMP2, 2 downstream targets repressed by NOTCH1. In rescue experiments, the transfection of a vector encoding for the active Notch intracellular domain prevented H19-induced mineralization of valve interstitial cells.Conclusions: These findings indicate that a dysregulation of DNA methylation in the promoter of H19 during calcific aortic valve disease is associated with a higher expression of this lncRNA, which promotes an osteogenic program by interfering with the expression of NOTCH1. [ABSTRACT FROM AUTHOR]