Effect of adipose-derived stem cells with overexpression or silencing of lncRNA SNHG8 on vascular endothelial cell dysfunction / 中国病理生理杂志

AIM:To investigate the effects of adipose-derived stem cells(ADSCs)with overexpression or si-lencing of long noncoding RNA(lncRNA)SNHG8 on the viability,migration,angiogenesis,and the expression of vasoac-tive factors in human umbilical vein endothelial cells(HUVECs).METHODS:Identification of ADSCs derived from morbidly obese patients(O-ADSCs)was conducted using flow cytometry and induction of lipogenesis and osteogenesis.The expression of lncRNA SNHG8 in healthy human ADSCs(H-ADSCs)and O-ADSCs was detected by RT-qPCR.Tran-swell method was used to establish the indirect co-culture system of ADSCs and HUVECs for 48 h,and the cells were di-vided into O-ADSCs+HUVECs group,H-ADSCs+HUVECs group,and HUVECs alone group.The mRNA and protein ex-pression levels of angiotensin Ⅱ(Ang Ⅱ),endothelin-1(ET-1)and endothelial nitric oxide synthase(eNOS)in HUVECs were detected by RT-qPCR and Western blot.The lncRNA SNHG8 overexpression and silencing lentiviruses were con-structed and used to infect O-ADSCs.The indirect co-cultured ADSCs and HUVECs were divided into O-ADSCs-OE-SNHG8+ HUVECs group,O-ADSCs-OE-NC+HUVECs group,O-ADSCs-sh-SNHG8+HUVECs group,and O-ADSCs-sh-NC+HUVECs group.After co-culture for 48 h,the viability,migration and tubule formation of HUVECs were detected by CCK-8,scratch and angiogenesis assays,respectively.The mRNA and protein expression levels of Ang Ⅱ,ET-1 and eNOS in HU-VECs were detected by RT-qPCR and Western blot,respectively.The nitrate reductase method was used to detect the con-tent of NO in HUVECs.RESULTS:(1)The cultured cells were identified as ADSCs.(2)Compared with H-ADSCs,ln-cRNA SNHG8 expression was significantly up-regulated in O-ADSCs(P<0.01).(3)Compared with H-ADSCs+HUVECs group and HUVECs group,the mRNA and protein expression levels of Ang Ⅱ and ET-1 in HUVECs in O-ADSCs+HU-VECs group were up-regulated(P<0.01).(4)Overexpression of lncRNA SNHG8 in O-ADSCs enhanced the viability,mi-gration and tube formation ability of HUVECs,up-regulated the mRNA and protein expression levels of Ang Ⅱ and ET-1,down-regulated the mRNA and protein expression levels of eNOS,and decreased the content of NO in HUVECs(P<0.05).However,silencing of lncRNA SNHG8 in O-ADSCs exerted opposite results(P<0.05).CONCLUSION:(1)The O-ADSCs can promote endothelial cell viability,migration and tubule formation through paracrine effects.(2)The O-ADSCs with overexpression of lncRNA SNHG8 promote the imbalance of diastolic and contractile factors secreted by endo-thelial cells,and induce the dysfunction of vascular endothelial cells.

Role of lncRNA RMRP in the proliferation and apoptosis of endometrial carcinoma cells through JAK/STAT signaling pathway / 局解手术学杂志

Objective To investigate the biological function and main molecular mechanism of long noncoding RNA RMRP(lncRNA RMRP)in endometrial carcinoma.Methods The specimens of carcinoma tissues and adjacent tissues of 30 patients with endometrial carcinoma who received surgical treatment in our hospital were collected.RT-qPCR was used to detect the expression of lncRNA RMRP in endometrial carcinoma tissues and adjacent tissues,and HESC cells and HEC-1-A cells.The endometrial carcinoma cell line HEC-1-A was cultured in vitro,and the Vector,pcDNA-RMRP,NC-siRNA,RMRP-siRNA,NC mimic,miR-580-3p mimic,pcDNA-RMRP+NC mimic,pcDNA-RMRP+ miR-580-3p mimic,RMRP-siRNA+Vector,RMRP-siRNA+pcDNA-JAK2,NC inhibitor,and miR-580-3p inhibitor were transfected into HEC-1-A cells as the Vector group,the pcDNA-RMRP group,the NC-siRNA group,the RMRP-siRNA group,the NC mimic group,the miR-580-3p mimic group,the pcDNA-RMRP+NC mimic group,the pcDNA-RMRP+miR-580-3p mimic group,the RMRP siRNA+Vector group,the RMRP-siRNA+pcDNA-JAK2 group,the NC inhibitor group,and the miR-580-3p inhibitor group respectively.RT-qPCR was used to detect the expression of lncRNA RMRP and miR-580-3p in cells.CCK-8 was used to detect cell proliferation rate.The apoptosis rate was detected by flow cytometry analysis.Bioinformatics software and dual luciferase reporter gene experiment were used to predict and verify the targeted relationships between miR-580-3p and lncRNA RMRP,as well as miR-580-3p and JAK2.Western blot was used to detect the protein expression of JAK/STAT signaling pathway.Results Compared with adjacent tissues,lncRNA RMRP was highly expressed in endometrial carcinoma tissues(P<0.05).Compared with HESC cells,the expression of lncRNA RMRP in HEC-1-A cells was significantly increased(P<0.05).pcDNA-RMRP significantly promoted cell proliferation and inhibited cell apoptosis,while RMRP-siRNA significantly inhibited cell proliferation and promoted cell apoptosis,with statistically significant diferences(P<0.05).miR-580-3p was the downstream target miRNA of lncRNA RMRP,and lncRNA RMRP could negatively regulate the expression of miR-580-3p.JAK2 was the downstream target gene of miR-580-3p,and miR-580-3p could negatively regulate the expression of JAK2 protein.pcDNA-RMRP significantly increased the protein levels of JAK2,p-JAK2 and p-STAT3 in the cells,while co-transfection of pcDNA-RMRP and miR-580-3p mimic significantly decreased the protein levels of JAK2,p-JAK2 and p-STAT3,with statistically significant diferences(P<0.05).RMRP-siRNA could signifi-cantly reduce the protein levels of JAK2,p-JAK2 and p-STAT3 in cells.After co-transfection of RMRP-siRNA and pcDNA-JAK2,the protein levels of JAK2,p-JAK2 and p-STAT3 were significantly increased,with statistically significant diferences(P<0.05).In addition,co-transfection of RMRP-siRNA and pcDNA-JAK2 increased cell proliferation and decreased cell apoptosis,with statistically significant diferences(P<0.05).Conclusion Knockdown of lncRNA RMRP could inhibit endometrial carcinoma cell proliferation and promote cell apoptosis by regulating JAK2/STAT3 signaling pathway,which might be a potential therapeutic target for endometrial carcinoma.

Effects of long noncoding RNA-NRON on apoptosis following myocardial infarction in mice / 中国医科大学学报

Objective To investigate the effects of long noncoding RNA(lncRNA)-NRON on apoptosis following myocardial infarc-tion(MI)in mice.Methods The C57BL/6 mice were randomly divided into four groups:sham operation(Sham)group,MI group,MI combined with lncRNA-NRON interference lentivirus(MI+shNRON)group,and MI combined with the negative control(NC)lentivirus(MI+NC)group.The expression of lncRNA-NRON was detected using real-time PCR.In addition,the pathology of the myocardial tissue injury was analyzed using HE staining,the myocardial infarction size was examined using TTC staining,and the extent of apoptosis was assessed using the TUNEL assay,respectively.The RPISeq database was used to predict the probability of interaction between lncR-NA-NRON and the voltage-dependent anionic channel protein(VDAC).The effect of lncRNA-NRON on the expression of VDAC protein was detected using Western blotting.Results The lncRNA-NRON expression was significantly increased in the MI group,and the tar-geted knockdown of lncRNA-NRON resulted in alleviation of the pathological myocardial tissue injury,reduction in the myocardial infarc-tion area,and inhibition of apoptosis.The probability of interaction between lncRNA-NRON and VDAC reached 0.9,indicating a high probability of their association.Additionally,lncRNA-NRON could regulate the protein expression of VDAC.Conclusion Knockdown of lncRNA-NRON could reduce the occurrence of myocardial injury following myocardial infarction.This effect may be attributable to a spe-cific mechanism wherein lncRNA-NRON affects the process of apoptosis by binding to VDAC,consequently suppressing its expression.

Regulatory function of long noncoding RNA MAGI2-AS3 in tumor development: a review / 预防医学

Abstract@#Long noncoding RNA (lncRNA) is closely related to the pathogenesis of cancer,representing a burgeoning field in tumor research in recent years. MAGI2-AS3, a tumor-associated lncRNA, exerts pivotal roles in epigenetics, transcription and post-transcriptional regulation. Studies have suggested that MAGI2-AS3 may be involved in multiple stages of tumor development, and has potential applications for tumor diagnosis, therapy and prognosis. This review summarizes the expression, regulatory mechanism and clinical application value of MAGI2-AS3 in common malignant tumrs, providing the reference for tumor prevention and treatment.

Role and mechanism of noncoding RNA in diabetic peripheral neuropathy / 中国组织工程研究

BACKGROUND:Persistent hyperglycemia has been identified as promoting neurovascular dysfunction,leading to irreversible endothelial dysfunction,increased neuronal apoptosis,oxidative stress and inflammation.These changes in combination or alone lead to microvascular and macrovascular lesions as well as progressive neuropathy.Noncoding RNAs may provide a new strategy for understanding the etiology,pathogenesis and treatment of the disease. OBJECTIVE:To review the role and mechanism of noncoding RNAs in the occurrence and development of diabetic peripheral neuropathy by reviewing relevant literature at home and abroad,in order to provide new ideas and approaches for noncoding RNAs in the prevention,diagnosis and treatment of diabetes neuropathy. METHODS:CNKI and PubMed were retrieved for relevant literature published from database inception to 2022.The key words were"noncoding RNA;lncRNA;miRNA;diabetes peripheral neuropathy;expression profile"in Chinese and English,respectively.The retrieved documents were summarized and analyzed,and 61 articles were finally selected for further review. RESULTS AND CONCLUSION:(1)Noncoding RNA plays a key role in the pathophysiological process of diabetic peripheral neuropathy.Among the most widely studied regulatory noncoding RNA species,there are long noncoding RNAs,circular RNAs and microRNAs.(2)Through the regulation of noncoding RNAs,the activation or inhibition of related cell pathways,inflammatory genes and downstream-related cytokines will inhibit cell apoptosis,improve inflammation,and thus change the expression of target genes to participate in the process of diabetic neuralgia.(3)Although many microRNAs and long noncoding RNAs have been found to participate in diabetic peripheral neuropathy,the mechanisms of many noncoding RNAs are unclear,and the same noncoding RNAs may play different roles in different modes.Therefore,it is necessary to further study their action modes in disease etiology and pathology,thereby clarifying their role in the pathogenesis of diabetic peripheral neuropathy.However,the criteria for evaluating noncoding RNA activity have not yet been established,and further research is needed on which specific noncoding RNAs play a dominant regulatory role.(4)MicroRNAs,long noncoding RNAs and their target genes can regulate progressive neuropathy,which are expected to become new targets for the clinical prevention and treatment of diabetic peripheral neuropathy and new biomarkers for the development and prognosis of diabetic peripheral neuropathy.

The lncSIL molecule exerts a negative regulatory effect on the alveolar epithelial-mesenchymal transition induced by TGF-β1 through modulation of the EZH2/P21/CDK6 signaling pathway / 安徽医科大学学报

Objective @#To investigate the role of lncSIL in transforming growth factor-β1(TGF-β1)-induced alveo- lar epithelial interstitial transformation (EMT) and its related signaling pathways .@*Methods @#Western blot was used to detect the effect of lncSIL silencing on the expression of E-cadherin ( E-cad) , alpha-smooth muscle actin ( α- SMA) and Collagen I (Col I) in the process of EMT induced by TGF-β1 . LncSIL interacting proteins were ana- lyzed by RNA pulldown . Western blot was used to detect the effect of overexpression or silencing of lncSIL on the expression of its target gene enhancer of zeste homolog 2 (EZH2) and its downstream factors P21 and cyclin-de- pendent kinase 6 (CDK6) . Flow cytometry was used to analyze the effect of lncSIL on cell cycle progression .@*Results@#After lncSIL silencing , the expression of α-SMA and Col I increased , the expression of E-cad decreased . RNA pulldown assay showed that EZH2 was the target protein that interacted with lncSIL , and the expression of EZH2 increased after silencing lncSIL , the expression of EZH2 downstream gene P21 decreased , CDK6 increased . Flow cytometry showed that the number of cells in S phase significantly increased . When lncSIL was overexpressed , the expression of EZH2 and CDK6 was down-regulated , the expression of P21 was up-regulated , and the number of S phase cells significantly decreased .@*Conclusion @#LncSIL inhibits TGF-β1-induced alveolar epithelial cell mesen- chymal transition by negatively regulating EZH2/P21 /CDK6 signaling pathway to inhibit cell cycle progression .

Down-regulation of long noncoding RNA HOXA11-AS nullifies the impact of microRNA-506-3p on chondrocytes proliferation and apoptosis in osteoarthritis

Abstract Objectives This study was directed towards exploring the impacts of lncRNA HOXA11-AS-mediated microRNA (miR)-506-3p on chondrocytes proliferation and apoptosis in osteoarthritis (OA). Methods The articular cartilages were provided by OA patients who received total knee arthroplasty, and Human Chondrocyte (HC)-OA (HC-OA) was also attained. The miR-506-3p and HOXA11-AS expressions in articular cartilages from OA patients and HC-OA cells were analyzed via qPCR. After gain- and loss-of-function assays in HC-OA cells, MTT assay and flow cytometry (FC) were used for assessing cell viability and apoptosis, accordingly. The levels of PIK3CA, AKT, and mTOR as well as AKT and mTOR phosphorylation levels assessed using western blotting (WB). The targeting correlation of HOXA11-AS and miR-506-3p as well as miR-506-3p and PIK3CA was assessed through Dual-Luciferase Reporter gene Assay (DLRA). Result The articular cartilages from OA patients and Human Chondrocyte (HC)-OA (HC-OA) cells showed increased HOXA11-AS and decreased miR-506-3p. Mechanistically, HOXA11-AS was capable of binding to miR-506-3p to increase PIK3CA, the target gene of miR-506-3p. miR-506-3p suppression facilitated HC-OA cell proliferation and reduced their apoptosis, which was nullified by further silencing HOXA11-AS or silencing PIK3CA. The down-regulation of HOXA11-AS disrupted the PI3K/AKT/mTOR pathway, which was counteracted by further miR-506-3p inhibition. Conclusion The silencing of HOXA11-AS might block the PI3K/AKT/mTOR pathway through miR-506-3p up-regulation, thereby restricting HC-OA cell proliferation and provoking apoptosis.

Regulation of Glial Function by Noncoding RNA in Central Nervous System Disease / 神经科学通报·英文版

Non-coding RNAs (ncRNAs) are a class of functional RNAs that play critical roles in different diseases. NcRNAs include microRNAs, long ncRNAs, and circular RNAs. They are highly expressed in the brain and are involved in the regulation of physiological and pathophysiological processes of central nervous system (CNS) diseases. Mounting evidence indicates that ncRNAs play key roles in CNS diseases. Further elucidating the mechanisms of ncRNA underlying the process of regulating glial function that may lead to the identification of novel therapeutic targets for CNS diseases.

Huangqi Decoction, a compound Chinese herbal medicine, inhibits the proliferation and activation of hepatic stellate cells by regulating the long noncoding RNA-C18orf26-1/microRNA-663a/transforming growth factor-β axis / 中西医结合学报

OBJECTIVE@#Huangqi Decoction (HQD), a classical traditional Chinese medicine formula, has been used as a valid treatment for alleviating liver fibrosis; however, the underlying molecular mechanism is still unknown. Although our previous studies showed that microRNA-663a (miR-663a) suppresses the proliferation and activation of hepatic stellate cells (HSCs) and the transforming growth factor-β/small mothers against decapentaplegic (TGF-β/Smad) pathway, whether long noncoding RNAs (lncRNAs) are involved in HSC activation via the miR-663a/TGF-β/Smad signaling pathway has not yet reported. The present study aimed to investigate the roles of lncRNA lnc-C18orf26-1 in the activation of HSCs and the mechanism by which HQD inhibits hepatic fibrosis.@*METHODS@#The expression levels of lnc-C18orf26-1, miR-663a and related genes were measured by quantitative reverse transcription-polymerase chain reaction. HSCs were transfected with the miR-663a mimic or inhibitor and lnc-C18orf26-1 small interfering RNAs. The water-soluble tetrazolium salt-1 assay was used to assess the proliferation rate of HSCs. Changes in lncRNA expression were evaluated in miR-663a-overexpressing HSCs by using microarray to identify miR-663a-regulated lncRNAs. RNA hybrid was used to predict the potential miR-663a binding sites on lncRNAs. Luciferase reporter assays further confirmed the interaction between miR-663a and the lncRNA. The expression levels of collagen α-2(I) chain (COL1A2), α-smooth muscle actin (α-SMA) and TGF-β/Smad signaling pathway-related proteins were determined using Western blotting.@*RESULTS@#Lnc-C18orf26-1 was upregulated in TGF-β1-activated HSCs and competitively bound to miR-663a. Knockdown of lnc-C18orf26-1 inhibited HSC proliferation and activation, downregulated TGF-β1-stimulated α-SMA and COL1A2 expression, and inhibited the TGF-β1/Smad signaling pathway. HQD suppressed the proliferation and activation of HSCs. HQD increased miR-663a expression and decreased lnc-C18orf26-1 expression in HSCs. Further studies showed that HQD inhibited the expression of COL1A2, α-SMA, TGF-β1, TGF-β type I receptor (TGF-βRI) and phosphorylated Smad2 (p-Smad2) in HSCs, and these effects were reversed by miR-663a inhibitor treatment.@*CONCLUSION@#Our study identified lnc-C18orf26-1 and miR-663a as promising therapeutic targets for hepatic fibrosis. HQD inhibits HSC proliferation and activation at least partially by regulating the lnc-C18orf26-1/miR-663a/TGF-β1/TGF-βRI/p-Smad2 axis.

Circulating Exosomal LncRNAs as Novel Diagnostic Predictors of Severity and Sites of White Matter Hyperintensities / 生物医学与环境科学（英文）

OBJECTIVE@#Exosomal long noncoding RNAs (lncRNAs) are the key to diagnosing and treating various diseases. This study aimed to investigate the diagnostic value of plasma exosomal lncRNAs in white matter hyperintensities (WMH).@*METHODS@#We used high-throughput sequencing to determine the differential expression (DE) profiles of lncRNAs in plasma exosomes from WMH patients and controls. The sequencing results were verified in a validation cohort using qRT-PCR. The diagnostic potential of candidate exosomal lncRNAs was proven by binary logistic analysis and receiver operating characteristic (ROC) curves. The diagnostic value of DE exo-lncRNAs was determined by the area under the curve (AUC). The WMH group was then divided into subgroups according to the Fazekas scale and white matter lesion site, and the correlation of DE exo-lncRNAs in the subgroup was evaluated.@*RESULTS@#In our results, four DE exo-lncRNAs were identified, and ROC curve analysis revealed that exo-lnc_011797 and exo-lnc_004326 exhibited diagnostic efficacy for WMH. Furthermore, WMH subgroup analysis showed exo-lnc_011797 expression was significantly increased in Fazekas 3 patients and was significantly elevated in patients with paraventricular matter hyperintensities.@*CONCLUSION@#Plasma exosomal lncRNAs have potential diagnostic value in WMH. Moreover, exo-lnc_011797 is considered to be a predictor of the severity and location of WMH.

Construction of prognostic risk model of bladder cancer based on cuproptosis-related long non-coding RNAs / 浙江大学学报·医学版

OBJECTIVES@#To construct a prognosis risk model based on long noncoding RNAs (lncRNAs) related to cuproptosis and to evaluate its application in assessing prognosis risk of bladder cancer patients.@*METHODS@#RNA sequence data and clinical data of bladder cancer patients were downloaded from the Cancer Genome Atlas database. The correlation between lncRNAs related to cuproptosis and bladder cancer prognosis was analyzed with Pearson correlation analysis, univariate Cox regression, Lasso regression, and multivariate Cox regression. Then a cuproptosis-related lncRNA prognostic risk scoring equation was constructed. Patients were divided into high-risk and low-risk groups based on the median risk score, and the immune cell abundance between the two groups were compared. The accuracy of the risk scoring equation was evaluated using Kaplan-Meier survival curves, and the application of the risk scoring equation in predicting 1, 3 and 5-year survival rates was evaluated using receiver operating characteristic (ROC) curves. Univariate and multivariate Cox regression were used to screen for prognostic factors related to bladder cancer patients, and a prognostic risk assessment nomogram was constructed, the accuracy of which was evaluated with calibration curves.@*RESULTS@#A prognostic risk scoring equation for bladder cancer patients was constructed based on nine cuproptosis-related lncRNAs. Immune infiltration analysis showed that the abundances of M0 macrophages, M1 macrophages, M2 macrophages, resting mast cells and neutrophils in the high-risk group were significantly higher than those in the low-risk group, while the abundances of CD8+ T cells, helper T cells, regulatory T cells and plasma cells in the low-risk group were significantly higher than those in the high-risk group (all P<0.05). Kaplan-Meier survival curve analysis showed that the total survival and progression-free survival of the low-risk group were longer than those of the high-risk group (both P<0.01). Univariate and multivariate Cox analysis showed that the risk score, age and tumor stage were independent factors for patient prognosis. The ROC curve analysis showed that the area under the curve (AUC) of the risk score in predicting 1, 3 and 5-year survival was 0.716, 0.697 and 0.717, respectively. When combined with age and tumor stage, the AUC for predicting 1-year prognosis increased to 0.725. The prognostic risk assessment nomogram for bladder cancer patients constructed based on patient age, tumor stage, and risk score had a prediction value that was consistent with the actual value.@*CONCLUSIONS@#A bladder cancer patient prognosis risk assessment model based on cuproptosis-related lncRNA has been successfully constructed in this study. The model can predict the prognosis of bladder cancer patients and their immune infiltration status, which may also provide a reference for tumor immunotherapy.

Long non-coding RNAs in infantile hemangioma / 中华皮肤科杂志

Long non-coding RNAs (lncRNAs) can affect various biological processes, such as cell proliferation, migration, and angiogenesis, by regulating chromosome remodeling, gene transcription or protein translation. This review summarizes recent research progress in the role of lncRNAs in the occurrence and development of infantile hemangioma, in order to provide new directions for the treatment of infantile hemangioma.

Effects of lncRNA NEAT1 silencing on microglial polarization via IL-10/STAT3 signaling pathway on cerebral ischemia reperfusion injury in rats / 中风与神经疾病杂志

@#Objective To investigate the effect of long noncoding RNA nuclear enriched abundant transcript 1 (lncRNA NEAT1) silencing on cerebral ischemia reperfusion injury (CIRI) in rats by regulating microglia polarization through interleukin (IL)-10/signal transducer and activator of transcription 3 (STAT3) signaling pathway.Methods SD rats were randomly divided into sham operation group (Sham group),CIRI group,CIRI+si-NC group,CIRI+si-NEAT1 group,each group of 24 rats.Except for the Sham group,the rats in the other groups were used to construct the CIRI model by thread occlusion method.After modeling,rats in each group were given corresponding treatments for 7 days.Neurological deficits of rats were scored; brain histopathological changes were observed; the percentage of cerebral infarction volume,the number of M1 and M2 polarization marker positive (Iba1+CD86+,Iba1+CD206+) cells in the positive cells of ionic calcic junction protein molecule 1 (Iba1+),IL-1β,tumor necrosis factor-α (TNF-α),IL-4,IL-10,lncRNA NEAT1,inducible nitric oxide synthase (iNOS),arginase-1 (Arg-1),IL-10 mRNA,IL-10,STAT3,phosphorylated STAT3 (p-STAT3) protein levels in rat brain tissue were detected.Results Compared with Sham group,the CIRI group showed severe pathological damage of brain tissue in rats,neurological deficit score,percentage of cerebral infarction volume,number of Iba1+CD86+,Iba1+CD206+ positive cells,CD86/CD206 ratio,IL-1β,TNF-α,IL-4,IL-10 levels,lncRNA NEAT1,iNOS,Arg-1,IL-10 mRNA levels,IL-10 and p-STAT3/STAT3 protein levels in brain tissue were significantly increased (P<0.05);compared with CIRI group and CIRI+si-NC group,CIRI+si-NEAT1 group had less pathological damage of brain tissue in rats,neurological deficit score,percentage of cerebral infarction volume,number of Iba1+CD86+ positive cells,CD86/CD206 ratio,IL-1β and TNF-α levels,lncRNA NEAT1,iNOS mRNA levels in brain tissue were significantly decreased (P<0.05),the number of Iba1+CD206+cells,IL-4,IL-10 levels,Arg-1,IL-10 mRNA,IL-10 and p-STAT3/STAT3 protein levels were significantly increased (P<0.05). Conclusion Silencing lncRNA NEAT1 may regulate microglial polarization by activating IL-10/STAT3 signaling pathway,thereby ameliorating brain tissue injury in CIRI rats.

Research advances of long noncoding RNA H19 in central nervous system diseases / 实用医学杂志

Central nervous system(CNS)is a complex system closely related to anesthesiology.The molecular biological mechanisms of many CNS diseases were not exactly clear.Long noncoding RNA(lncRNA)H19 is abun-dant in human brain and plays an important role in the regulation of various CNS diseases.Besides,lncRNA H19 is also involved in the mechanism of several anesthetics.In this review,we emphasized the role and addressed the specific mechanisms of lncRNA H19 in CNS diseases and anesthetics,hoping to provide a new theoretical basis for future researches.

Progress of Research on Long Noncoding RNA in Digestive System Tumors / 胃肠病学

The incidence and mortality of digestive system tumors are high,and the trend is increasing year by year,and the early onset is hidden,difficult to detect,and seriously threaten human health.In recent years,it has been found that long noncoding RNA(lncRNA),as a new class of non-coding RNA,plays an important role in the occurrence and development of tumors,influencing the occurrence and development of tumors by regulating the malignant biological characteristics of tumor cells such as proliferation,invasion and metastasis.Further study on the role of lncRNA in digestive system tumors can further discover its diagnosis and treatment methods,and provide new ideas for reducing the incidence and mortality of digestive system tumors.This article reviewed the progress of research in lncRNA in digestive system tumors.

Identification of LHFPL3-AS2 as a prognostic biomarker in lung adenocarcinoma

Background: Deregulation of long noncoding RNAs (lncRNAs) was considered one of the main characteristics of several human cancers. However, detailed genome-wide expression and functional significance studies of lnc RNAs in lung adenocarcinoma are still limited. This study aims to discover a new lncRNA that may play an important role in regulating the pathogenesis of lung adenocarcinoma (ADC). Methods: We conducted a comprehensive analysis of three Gene Expression Omnibus (GEO) microarray datasets and TCGA datasets. Differentially expressed lncRNAs between ADC and normal tissues were screened and verified using Gene Expression Profiling Interactive Analysis (GEPIA). Moreover, Kaplan-Meier plotter was used to construct the gene prognosis profile. The downstream targets of miRNA and related functional pathways were predicted and validated. Results: With microarray gene expression analysis, we found that only lncRNAs-PCAT6 was commonly upregulated among four datasets, and four lncRNAs (LINC00968, PGM5-AS1, LHFPL3-AS2 and SFTA1P) were significantly downregulated in the ADC samples as compared to the normal tissues. Meanwhile, for LHFPL3-AS2, high-risk patients showed better overall survival (HR=0.6 or 0.62; P < .0001 or P = 0.0014), overall survival from TCGA datasets (HR=0.72; P = 0.015) and recurrence-free survival (HR=0.72; P = 0.015). Then, LHFPL3-AS2 was predicted to bind to two miRNAs, miR-127-5p and miR-424-5p. Finally, validation and functional enrichment analysis of the downstream key mRNAs showed significant enrichment in some cancer-related pathways, such as cell adhesion in cancer and small cell lung cancer. Conclusions: Taken together, our study indicated that LHFPL3-AS2 was associated with tumorigenesis, and it could be used as a useful biomarker in the diagnosis, prognosis and treatment of ADC.

Diagnostic and prognostic significance of long noncoding RNA LINC00173 in patients with melanoma

SUMMARY OBJECTIVE: A growing volume of literature has suggested long noncoding RNAs (lncRNAs) as important players in tumor progression. In this study, we aimed to investigate the expression and prognostic value of lncRNA LINC00173 (LINC00173) in melanoma. METHODS: LINC00173 expression was measured in 163 paired cancerous and noncancerous specimen samples by real-time polymerase chain reaction. The correlations between LINC00173 expression with clinicopathological characteristics and prognosis were analyzed by chi-square test, log-rank test, and multivariate survival analysis. Receiver-operating characteristic curves were used for the assessment of the diagnostic value of LINC00173 for melanoma patients. RESULTS: The expression level of LINC00173 in melanoma specimens was distinctly higher than that in adjacent non-neoplasm specimens (p<0.01). Besides, LINC00173 was expressed more frequently in patients with advanced melanoma than in patients with early melanoma. Multivariate assays confirmed that LINC00173 expression level was an independent prognostic predictor of melanoma patients (p<0.05). CONCLUSION: Our data indicated that LINC00173 expression could serve as an unfavorable prognostic biomarker for melanoma patients.

Study on long noncoding RNA LBX2-AS1 regulates glioma cell proliferation, migration and apoptosis through epidermal growth factor receptor signaling pathway / 中国医师进修杂志

Objective:To investigate the mechanism of long noncoding RNA (lncRNA) LBX2-AS1 regulating glioma cell proliferation, migration and apoptosis through epidermal growth factor receptor (EGFR) signaling pathway.Methods:From April 2018 to August 2021, glioma U251 cells (U251 cells for short) were divided into control group and observation group, with 4 strains in each group. The control group was routinely cultured, and the observation group was transfected with specific small interfering RNA (siRNA) targeting LBX2-AS1. The proliferation ability of U251 cells was detected by methyl thiazol tetrazolium method, the metastasis rate of U251 cells was detected by scratch test, the apoptosis rate of U251 cells was detected by flow cytometry, and the expression of total protein and vascular endothelial growth factor (VEGF), phosphorylated inositol 3 kinase (p-PI3K), phosphorylated protein kinase B (p-Akt), phosphorylated Ras (p-Ras) and phosphorylated Raf (p-Raf) protein were detected by Western blot.Results:The proliferation ability and metastasis rate of U251 cells in observation group were significantly lower than those in control group: (27.15 ± 1.38)% vs. (63.54 ± 2.47)% and (37.09 ± 3.74)% vs. (82.17 ± 9.24)%, the apoptosis rate of U251 cells was significantly higher than that in control group: (69.17 ± 5.83)% vs. (17.58 ± 1.22)%, and there were statistical differences ( P<0.01). The expression of total protein and VEGF, p-PI3K, p-Akt, p-Ras, p-Raf protein of U251 cells in observation group were significantly lower than those in control group (1.52 ± 0.23 vs. 2.39 ± 0.31, 0.73 ± 0.08 vs. 1.68 ± 0.45, 0.57 ± 0.11 vs. 1.89 ± 0.31, 0.68 ± 0.06 vs. 1.74 ± 0.51, 0.84 ± 0.12 vs. 1.99 ± 0.63 and 0.71 ± 0.08 vs. 1.52 ± 0.37), and there were statistical differences ( P<0.01). Conclusions:The lncRNA LBX2-AS1 is highly expressed in glioma cells. Silencing the expression of lncRNA LBX2-AS1 inhibits the proliferation and metastasis of glioma cells through EGFR pathway.

LncRNA-m18as1 competitively binds with miR-18a-5p to regulate follicle-stimulating hormone secretion through the Smad2/3 pathway in rat primary pituitary cells / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Long noncoding RNAs (lncRNAs) are expressed in different species and different tissues, and perform different functions, but little is known about their involvement in the synthesis or secretion of follicle-stimulating hormone (FSH). In general, we have revealed lncRNA‍‒‍microRNA (miRNA)‍‒‍‍messenger RNA (mRNA) interactions that may play important roles in rat primary pituitary cells. In this study, a new lncRNA was identified for the first time. First, we analyzed the gene expression of lncRNA-m18as1 in different tissues and different stages by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and observed the localization of lncRNA-m18as1 with fluorescence in situ hybridization, which indicated that this lncRNA was distributed mainly in the cytoplasm. Next, we used RT-qPCR and enzyme-linked immunosorbent assay (ELISA) to analyze the regulation of FSH synthesis and secretion after overexpression or knockdown of lncRNA-m18as1 and found that lncRNA-m18as1 was positively correlated with FSH synthesis and secretion. In addition, mothers against decapentaplegic homolog 2 (Smad2) was highly expressed in our sequencing results. We also screened miR-18a-5p from our sequencing results as a miRNA that may bind to lncRNA-m18as1 and Smad2. We used RNA immunoprecipitation-qPCR (RIP-qPCR) and/or dual luciferase assays to confirm that lncRNA-m18as1 interacted with miR-18a-5p and miR-18a-5p interacted with Smad2. Fluorescence in situ hybridization (FISH) showed that lncRNA-m18as1 and miR-18a-5p were localized mainly in the cytoplasm. Finally, we determined the relationship among lncRNA-m18as1, miR-18a-5p, and the Smad2/3 pathway. Overall, we found that lncRNA-m18as1 acts as a molecular sponge of miR-18a-5p to regulate the synthesis and secretion of FSH through the Smad2/3 pathway.

Analysis of Therapeutic Approaches and Potential Targets of Rosuvastatin on Myocardial Injury in Diabetic Rats Based on LncRNA Sequencing / 中国生物化学与分子生物学报

Statins can bring some benefits to the treatment of diabetic cardiomyopathy (DCM), but the specific molecular pathway of their action is still unclear. Recent studies have shown that abnormal expression of long noncoding RNA (lncRNA) is closely related to the pathological development of DCM. To compare the degree of myocardial injury between diabetic rats treated with rosuvastatin and rats treated with conventional therapy, the therapeutic pathway and potential target of rosuvastatin on DCM was investigated. Total RNA of DCM rats was extracted and 1ncRNA microarray was prepared to screen out differentially expressed 1ncRNA and bioinformatics analysis was carried out. The results showed that 770 target genes were up-regulated and 884 were down-regulated in the treatment group compared with the model group, which were mainly related to improvement of metabolic disorder, regulation of the ratio of myocardial cells to collagen fibers, reduction of myocardial injury and exercise burden, prevention of autonomic nervous system and microcirculation diseases and change of eating habits. The signaling pathways involved are mainly concentrated in sensory pathways, signal transduction, lipid metabolism and so on. It is suggested that rosuvastatin may play a role in the treatment of DCM by regulating the participation of 1ncRNA in glucose and lipid energy metabolism and ion balance, inhibiting the process of myocardial fibrosis and improving the effect of high glucose toxicity on autonomic nervous function.