Effects of long non-coding RNA myocardial infarction-associated transcript on retinal neovascularization in a newborn mouse model of oxygen-induced retinopathy

Whether long non-coding RNA myocardial infarction-associated transcript is involved in oxygen-induced retinopathy remains poorly understood. To validate this hypothesis, we established a newborn mouse model of oxygen-induced retinopathy by feeding in an oxygen concentration of 75 ± 2% from postnatal day 8 to postnatal day 12, followed by in normal air. On postnatal day 11, the mice were injected with the myocardial infarction-associated transcript siRNA plasmid via the vitreous cavity to knockdown long non-coding RNA myocardial infarction-associated transcript. Myocardial infarction-associated transcript siRNA transcription significantly inhibited myocardial infarctionassociated transcript mRNA expression, reduced the phosphatidylinosital-3-kinase, phosphorylated Akt and vascular endothelial growth factor immunopositivities, protein and mRNA expression, and alleviated the pathological damage to the retina of oxygen-induced retinopathy mouse models. These findings suggest that myocardial infarction-associated transcript is likely involved in the retinal neovascularization in retinopathy of prematurity and that inhibition of myocardial infarction-associated transcript can downregulate phosphatidylinosital-3-kinase, phosphorylated Akt and vascular endothelial growth factor expression levels and inhibit neovascularization. This study was approved by the Animal Ethics Committee of Shengjing Hospital of China Medical University, China(approval No. 2016 PS074 K) on February 25, 2016.

Expression of long non-coding RNAs in complete transection spinal cord injury: a transcriptomic analysis

Long non-coding RNAs(lncRNAs)are abundantly expressed in the central nervous system and exert a critical role in gene regulation via multiple biological processes.To uncover the functional significance and molecular mechanisms of lncRNAs in spinal cord injury(SCI),the expression signatures of lncRNAs were profiled using RNA sequencing(RNA-seq)technology in a Sprague-Dawley rat model of the 10th thoracic vertebra complete transection SCI.Results showed that 116 of 14,802 detected lncRNAs were differentially expressed,among which 16—including eight up-regulated(H19,Vof16,Hmox2-ps1,LOC100910973,Ybx1-ps3,Nnat,Gcgr,LOC680254)and eight down-regulated(Rmrp,Terc,Ngrn,Ppp2r2b,Cox6a2,Rpl37a-ps1,LOC360231,Rpph1)—demonstrated fold changes>2 in response to transection SCI.A subset of these RNA-seq results was validated by quantitative real-time PCR.The levels of 821 mRNAs were also significantly altered post-SCI;592 mRNAs were up-regulated and 229 mRNAs were down-regulated by more than 2-fold.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses showed that differentially expressed mRNAs were related to GO biological processes and molecular functions such as injury and inflammation response,wound repair,and apoptosis,and were significantly enriched in 15 KEGG pathways,including cell phagocytosis,tumor necrosis factor alpha pathway,and leukocyte migration.Our results reveal the expression profiles of lncRNAs and mRNAs in the rat spinal cord of a complete transection model,and these differentially expressed lncRNAs and mRNAs represent potential novel targets for SCI treatment.We suggest that lncRNAs may play an important role in the early immuno-inflammatory response after spinal cord injury.This study was approved by the Administration Committee of Experimental Animals,Guangdong Province,China.

Regulatory mechanisms of long non-coding RNAs

Long non-coding RNAs(lncRNAs) belong to a large and complex family of RNAs, which play many important roles in regulating gene expression. However, the mechanism underlying the dynamic expression of lncRNAs is still not very clear. In order to identify lncRNAs and clarify the mechanisms involved, we collected basic information and highlighted the mechanisms underlying lncRNA expression and regulation. Overall, lncRNAs are regulated by several similar transcription factors and protein-coding genes. Epigenetic modification(DNA methylation and histone modification) can also downregulate lncRNA levels in tissues and cells. Moreover, lncRNAs may be degraded or cleaved via interaction with miRNAs and miRNAassociated protein complexes. Furthermore, alternative RNA splicing(AS) may play a significant role in the post-transcriptional regulation of lncRNAs.

Exosome-transported IncRNA H19 regulates insulin-like growth factor-1 via the H19/let-7a/insulin-like growth factor-1 receptor axis in ischemic stroke

LncRNA(long non-coding RNA) H19 is a transcript of the H19 gene that is expressed during embryogenesis.We previously discove red a role for circular lncRNA H19 in the onset and prognosis of cerebral ischemic stroke.In this study,we used serum from patients with ischemic stroke,and mouse and cell culture models to elucidate the roles of plasma and neuronal exosomes in the regulatory effect of lncRNA H19 on insulin-like growth factor-1 and its mechanism in ischemic stroke,using western blotting,quantitative real-time polymerase chain reaction,and enzyme-linked immunosorbent assays.Plasma exosomal IncRNA H19 was negatively associated with blood levels of insulin-like growth factor-1 in samples from patients with cerebral ischemic stroke.In a mouse model,levels of exosomal IncRNA H19 were positively correlated with plasma and cerebral lncRNA H19.In a cell co-culture model,we confirmed that IncRNA H19 was transported from neuro ns to astrocytes by exosomes to induce downregulation of insulin-like growth factor-1 through the H19/let-7 a/insulin-like growth factor-1 receptor axis.This study provides the first evidence for the transpo rtation of IncRNA H19 by exosomes and the relationship between IncRNA H19 and insulinlike growth factor-1.

Danhongqing formula alleviates cholestatic liver fibrosis by downregulating long non-coding RNA H19 derived from cholangiocytes and inhibiting hepatic stellate cell activation

Objective:This study explores the mechanism of action of Danhongqing formula(DHQ),a compoundbased Chinese medicine formula,in the treatment of cholestatic liver fibrosis.Methods:In vivo experiments were conducted using 8-week-old multidrug resistance protein 2 knockout(Mdr2-/-)mice as an animal model of cholestatic liver fibrosis.DHQ was administered orally for 8 weeks,and its impact on cholestatic liver fibrosis was evaluated by assessing liver function,liver histopathology,and the expression of liver fibrosis-related proteins.Real-time polymerase chain reaction,Western blot,immunohistochemistry and other methods were used to observe the effects of DHQ on long non-coding RNA H19(H19)and signal transducer and activator of transcription 3(STAT3)phosphorylation in the liver tissue of Mdr2-/-mice.In addition,cholangiocytes and hepatic stellate cells(HSCs)were cultured in vitro to measure the effects of bile acids on cholangiocyte injury and H19 expression.Cholangiocytes overexpressing H19 were constructed,and a conditioned medium containing H19 was collected to measure its effects on STAT3 protein expression and cell activation.The intervention effect of DHQ on these processes was also investigated.HSCs overexpressing H19 were constructed to measure the impact of H19 on cell activation and assess the intervention effect of DHQ.Results:DHQ alleviated liver injury,ductular reaction,and fibrosis in Mdr2-/-mice,and inhibited H19expression,STAT3 expression and STAT3 phosphorylation.This formula also reduced hydrophobic bile acid-induced cholangiocyte injury and the upregulation of H19,inhibited the activation of HSCs induced by cholangiocyte-derived conditioned medium,and decreased the expression of activation markers in HSCs.The overexpression of H19 in a human HSC line confirmed that H19 promoted STAT3 phosphorylation and HSC activation,and DHQ was able to successfully inhibit these effects.Conclusion:DHQ effectively alleviated spontaneous cholestatic liver fibrosis in Mdr2-/-mice by inhibiting H19 upregulation in cholangiocytes and preventing the inhibition of STAT3 phosphorylation in HSC,thereby suppressing cell activation.

LncRNA AFAP1-AS1 exhibits oncogenic characteristics and promotes gemcitabine-resistance of cervical cancer cells through miR-7-5p/EGFR axis

Background:Drug resistance is the main factor contributing to cancer recurrence and poor prognosis.Exploration of drug resistance-related mechanisms and effective therapeutic targets are the aim of molecular targeted therapy.In our study,the role of long non-coding RNA(lncRNA)AFAP1-AS1 in gemcitabine resistance and related mechanisms were explored in cervical cancer cells.Methods:Gemcitabine-resistant cervical cancer cell lines HT-3-Gem and SW756-Gem were constructed using the gemcitabine concentration gradient method.The overall survival rates and recurrence-free survival rates were evaluated by Kaplan-Meier analysis.The interaction was verified through a Dual-luciferase reporter gene assay and a Biotinylated RNA pull-down assay.Cell proliferation ability was assessed through methyl-thiazolyl-tetrazolium(MTT),soft agar,and colony formation experiments.Cell cycle and apoptosis were detected byflow cytometry.Results:Up-regulation of AFAP1-AS1 in cervical cancer predicted a poor prognosis.Besides,patients in the gemcitabine-resistance group had higher levels of AFAP1-AS1 than the gemcitabine-sensitive group.AFAP1-AS1 promoted tumor growth and induced gemcitabine tolerance of cervical cancer cells.In addition,AFAP1-AS1 mediated epidermal growth factor receptor(EGFR)expression by serving as a molecular sponge for microRNA-7a-5p(miR-7-5p).This present study also proved that the knockdown of EGFR or overexpression of miR-7a-5p abolished the accelerative role of AFAP1-AS1 overexpression in cancer progression and gemcitabine tolerance.Conclusions:In general,the AFAP1-AS1/miR-7-5p/EGFR axis was tightly related to the progression and gemcitabine tolerance of cervical cancer,providing potential targets for the management of cervical cancer.

The long non-coding RNA DANA2 positively regulates drought tolerance by recruitingERF84 to promote JMJ29-mediated histone demethylation

Tens of thousands of long non-coding RNAs have been uncovered in plants,but few of them have been comprehensively studied for their biological function and molecular mechanism of their mode of action.Here,we show that the Arabidopsis long non-coding RNA DANA2 interacts with an AP2/ERF transcription factor ERF84 in the cell nucleus and then affects the transcription of JMJ29 that encodes a Jumonji C domain-containing histone H3K9 demethylase.Both RNA sequencing(RNA-seq)and genetic analyses demonstrate that DANA2 positively regulates drought stress responses through JMJ29.JMJ29 positively regulates the expression of ERF15 and GOLS2 by modulation of H3K9me2 demethylation.Accordingly,mutation of JMJ29 causes decreased ERF15 and GOLS2 expression,resulting in impaired drought tolerance,in agreement with drought-sensitive phenotypes of dana2 and erf84 mutants.Taken together,these results demonstrate that DANA2 is a positive regulator of drought response and works jointly with the transcriptional activator ERF84 to modulate JMJ29 expression in plant response to drought.

Long non-coding RNAs in cardiac fibrosis:Regulation of cardiac fibroblasts

Background Cardiac fibrosis,characterized by excessive extracellular matrix(ECM)deposition and increased cardiac fibroblasts(CFs)activity,is a common pathology of various cardiovascular diseases.Cardiac fibrosis decreases ventricular compliance,increases diastolic filling pressure,decreases cardiac oxygen supply,and ultimately impairs the cardiac output.CFs are the main effecter cell type in regulating ECM and predominantly drive the fibrosis process.Despite the critical importance of CFs,our limited understanding of CFs impedes the development of potential therapies that effectively target this cell type and its pathological contribution to disease progression.Recently,long non-coding RNAs(lncRNAs)are emerging as important pathological and physiological regulators of cardiac fibrosis,shedding light on novel molecular mechanisms and potential therapeutic targets.This review discussed the current knowledge regarding the lnc RNAs involved in cardiac fibrosis and summarized their possible molecular mechanisms with special focus on the regulation of CFs.

Inhibition of LncRNA Vof-16 expression promotes nerve regeneration and functional recovery after spinal cord injury

Our previous RNA sequencing study showed that the long non-coding RNA ischemia-related factor Vof-16(lncRNA Vof-16)was upregulated after spinal cord injury,but its precise role in spinal cord injury remains unclear.Bioinformatics predictions have indicated that lncRNA Vof-16 may participate in the pathophysiological processes of inflammation and apoptosis.PC12 cells were transfected with a pHBLV-U6-MCS-CMV-ZsGreen-PGK-PURO vector to express an lncRNA Vof-16 knockdown lentivirus and a pHLV-CMVIE-ZsGree-Puro vector to express an lncRNA Vof-16 overexpression lentivirus.The overexpression of lncRNA Vof-16 inhibited PC12 cell survival,proliferation,migration,and neurite extension,whereas lncRNA Vof-16 knockdown lentiviral vector resulted in the opposite effects in PC12 cells.Western blot assay results showed that the overexpression of lncRNA Vof-16 increased the protein expression levels of interleukin 6,tumor necrosis factor-α,and Caspase-3 and decreased Bcl-2 expression levels in PC12 cells.Furthermore,we established rat models of spinal cord injury using the complete transection at T10.Spinal cord injury model rats were injected with the lncRNA Vof-16 knockdown or overexpression lentiviral vectors immediately after injury.At 7 days after spinal cord injury,rats treated with lncRNA Vof-16 knockdown displayed increased neuronal survival and enhanced axonal extension.At 8 weeks after spinal cord injury,rats treated with the lncRNA Vof-16 knockdown lentiviral vector displayed improved neurological function in the hind limb.Notably,lncRNA Vof-16 knockdown injection increased Bcl-2 expression and decreased tumor necrosis factor-αand Caspase-3 expression in treated animals.Rats treated with the lncRNA Vof-16 overexpression lentiviral vector displayed opposite trends.These findings suggested that lncRNA Vof-16 is associated with the regulation of inflammation and apoptosis.The inhibition of lncRNA Vof-16 may be useful for promoting nerve regeneration and functional recovery after spinal cord injury.The experiments were approved by the Institutional Animal Care and Use Committee of Guangdong Medical University,China.

Myogenesis controlled by a long non-coding RNA 1700113A16RIK and post-transcriptional regulation

Long non-coding(lnc)RNA plays important roles in many cellular processes.The function of the vast majority of lncRNAs remains unknown.Here we identified that lncRNA-1700113A16RIK existed in skeletal muscle stem cells(MuSCs)and was significantly elevated during MuSC differentiation.Knockdown of 1700113A16RIK inhibits the differentiation of muscle stem cells.In contrast,overexpression of 1700113A16RIK promotes the differentiation of muscle stem cells.Further study shows the muscle specific transcription factor Myogenin(MyoG)positively regulates the expression of 1700113A16RIK by binding to the promoter region of 1700113A16RIK.Mechanistically,1700113A16RIK may regulate the expression of myogenic genes by directly binding to 3’UTR of an important myogenic transcription factor MEF2D,which in turn promotes the translation of MEF2D.Taken together,our results defined 1700113A16RIK as a positive regulator of MuSC differentiation and elucidated a mechanism as to how 1700113A16RIK regulated MuSC differentiation.

Study on the relationship between the expression of NFκB1 and LncRNA-PACER in peripheral blood mononuclear cells of patients with pulmonary tuberculosis

Objective: To investigate the expression relationship between nuclear transcription factor kappa B1 (NFκB1) and long non-coding RNA PACER (LncRNA-PACER) in peripheral blood mononuclear cells (PBMCs) of patients with pulmonary tuberculosis. Methods: From February 2018 to March 2019, 40 patients with pulmonary tuberculosis (tuberculosis group) and 40 healthy persons (control group) were collected, the levels of TNF-α, IL-6 and IL-8 in serum were detected by enzyme-linked immunosorbent assay (ELISA);the expressions of LncRNA-PACER and NFκB1 mRNAs in PBMCs were detected by real-time fluorescence quantitative PCR;Western blot was used to detect the expressions of NFκB1 and COX 2 in PBMCs;Pearson method was used to analyze the expressions of LncRNA-PACER and NFκB1 in PBMCs of patients with pulmonary tuberculosis, and the expressions of LncRNA-PACER and NFκB1 in PBMCs of patients with pulmonary tuberculosis were analyzed. Results: Compared with the control group, the expressions of TNF-α, IL-6 and IL-8 in the serum of patients with pulmonary tuberculosis was significantly increased (P<0.05), and the expressions of LncRNA-PACER, NFκB1 mRNAs, proteins and COX-2 protein in PBMCs were significantly increased (P<0.05). The expressions of LncRNA-PACER and NFκB1 proteins in PBMCs were related to the number of pulmonary lesions and pulmonary cavity (P<0.05), and there was a positive correlation between the expression of LncRNA-PACER and the expression of NFκB1 mRNA in PBMCs of patients with pulmonary tuberculosis (r = 0.873, P<0.05). Conclusions: The expressions of NFκB1 and LncRNA-PACER in PBMCs of patients with pulmonary tuberculosis are significantly increased, they are positively correlated and both of them are related to the occurrence and development of pulmonary tuberculosis.

lncRNA CHRF与NT-proBNP对急性缺血性脑卒中患者并发脑心综合征的预测价值

目的探讨长链非编码RNA心脏肥大相关因子(lncRNA CHRF)与N末端B型利钠肽原(NT-proBNP)对急性缺血性脑卒中(AIS)患者并发脑心综合征(CCS)的预测价值。方法选取2021年11月至2023年10月该院收治的AIS患者121例为研究对象,按住院期间是否并发CCS分为CCS组(n=49)与无CCS组(n=72),比较两组临床指标及lncRNA CHRF、NT-proBNP水平。采用Pearson进行相关性分析,多因素logistic回归分析AIS并发CCS的影响因素,绘制受试者工作特征(ROC)曲线分析相关指标的预测价值。结果CCS组年龄、血肌酐、超敏C反应蛋白(hs-CRP)、肌酸激酶同工酶(CK-MB)、心肌肌钙蛋白I(cTnI)、lncRNA CHRF、NT-proBNP水平高于无CCS组(P<0.05),左心室射血分数(LVEF)低于无CCS组(P<0.05)。相关性分析显示,AIS并发CCS患者的lncRNA CHRF与NT-proBNP水平呈正相关(P=0.040);lncRNA CHRF、NT-proBNP水平与CK-MB、cTnI、hs-CRP水平均呈正相关(P<0.05),与LVEF呈负相关(P<0.05)。多因素logistic回归分析显示,LVEF降低、lncRNA CHRF升高、NT-proBNP升高是AIS患者并发CCS的独立危险因素(P<0.05)。ROC曲线分析显示,lncRNA CHRF、NT-proBNP单独及联合的曲线下面积(AUC)分别为0.673、0.711、0.850。结论AIS患者并发CCS的lncRNA CHRF、NT-proBNP明显升高,二者联合检测有较高的预测价值。

LncRNA Terc在心肌纤维化过程中的功能研究

目的:探讨lncRNA端粒酶RNA组分(Terc)在心肌纤维化(MF)过程中的作用。方法:使用不同浓度的TGF-β1诱导心肌成纤维细胞(CFs)转分化,通过免疫荧光染色、western blot检测α-SMA、Vimentin、Collagen I、Collagen III蛋白的表达水平,qRT-PCR检测lncRNA Terc表达水平。过表达和敲减Terc后,通过western blot、CCK-8和流式细胞术观察模型细胞的胞外基质产生、细胞增殖、凋亡和Smads信号传导情况。皮下注射异丙肾上腺素(ISO)构建小鼠心肌纤维化模型,并使用Terc敲低慢病毒干预,其后多普勒超声仪检测小鼠的心脏射血分数(EF)和左室短轴缩短率(FS),称量小鼠心脏湿重,HE、Masson染色检测小鼠心脏的病理改变,IHC检测α-SMA、Vimentin蛋白的表达水平,qRT-PCR检测lncRNA Terc表达水平。结果:TGF-β1处理增加CFs的α-SMA、Vimentin、Collagen I、Collagen III的蛋白表达以及Terc水平;过表达Terc促进α-SMA、Vimentin、Collagen I、Collagen III的蛋白表达以及Smad2/3的磷酸化水平,同时还可促进CFs的增殖、抑制CFs的凋亡;敲减Terc则起相反的作用;动物模型中,ISO可抑制EF和FS,增加心脏湿重,加重心肌的病理损伤,而敲减Terc可有效缓解上述过程。结论:LncRNA Terc可通过促进Smads信号传导,加速心肌成纤维细胞转分化和心肌纤维化进展。

长链非编码RNA MYOSLID 在急性心肌梗死患者血清中的水平及临床意义

目的探究长链非编码RNA(lncRNA)MYOSLID在急性心肌梗死(AMI)患者血清中的表达及其临床意义。方法选取2019年1月至2021年7月收治的95例AMI患者为AMI组,另选取同期95例健康体检者为对照组。比较两组基本资料;实时荧光定量PCR(qRT-PCR)法检测血清lncRNA MYOSLID表达水平,酶联免疫吸附法(ELISA)测定血清转化生长因子-β1(TGF-β1)水平,荧光免疫吸附法测定血清肌酸激酶同工酶-MB(CK-MB)水平,电化学发光法测定血清心肌肌钙蛋白I(cTnI)水平;Pearson法分析AMI患者血清lncRNA MYOSLID、TGF-β1水平与CK-MB、cTnI的相关性。结果AMI组患者总胆固醇(TG)、白细胞计数、低密度脂蛋白胆固醇(LDL-C)、中性粒细胞计数、CK-MB、总胆固醇(TC)、cTnI高于对照组(P<0.05),血清lncRNA MYOSLID、TGF-β1水平低于对照组(P<0.05);AMI患者血清lncRNA MYOSLID、TGF-β1水平与CK-MB、cTnI水平均呈负相关(P<0.05)。AMI患者血清lncRNA MYOSLID表达水平与TGF-β1呈正相关(P<0.05)。结论AMI患者血清lncRNA MYOSLID表达水平较低,与CK-MB、TGF-β1、cTnI显著相关,lncRNA MYOSLID可能是治疗AMI的潜在靶点。

长链非编码RNA Dnm3os在心肌成纤维细胞活化中的作用研究

长链非编码RNA(lncRNA)Dnm3os在肌腱周围组织纤维化和肺纤维化中发挥了重要作用,但其是否参与心肌纤维化过程,目前尚不清楚。为此,本研究利用课题组前期通过胸主动脉缩窄术(TAC)所致的小鼠纤维化模型的心脏组织,以及转化生长因子-β1(TGF-β1)所诱导的体外心肌成纤维细胞活化模型,采用定量聚合酶链式反应(RT-qPCR)、蛋白质印迹法(Western blot)及胶原凝胶收缩等方法,对心肌成纤维细胞活化表型和Dnm3os的表达变化进行鉴定和检测。并通过RNA干扰技术来沉默Dnm3os,以探究其在心肌成纤维细胞活化过程中的作用。结果表明,Dnm3os在小鼠纤维化心肌组织和体外培养活化的心肌成纤维细胞中均表达升高,而沉默其表达则可明显缓解心肌成纤维细胞活化。此外,TGF-β1/Smad2/3通路在心肌成纤维细胞活化过程中被激活;而沉默Dnm3os后,该通路受到抑制。本研究的结果提示,沉默Dnm3os可通过抑制TGF-β1/Smad2/3信号通路来影响心肌成纤维细胞的活化过程。因此,干预lncRNA Dnm3os的表达可能成为治疗心肌纤维化的潜在靶点。

Mechanisms of Huangqi Decoction Granules (黄芪汤颗粒剂) on Hepatitis B Cirrhosis Patients Based on RNA-Sequencing

Objective: To explore the action mechanisms of Huangqi Decoction Granules(黄芪汤颗粒剂, HQDG) on hepatitis B cirrhosis. Methods: A total of 85 patients with hepatitis B cirrhosis were randomly divided into HQDG group(42 cases) and control group(43 cases) by a random number table and were treated with HQDG or placebo for 48 weeks(6 g per times and orally for 3 times a day), respectively. After RNA-sequencing of serum samples extracted from the patients, the differentially expressed genes(DEGs) in HQDG and control groups before and after treatment were separately screened. The DEGs were then performed pathway enrichment analysis and proteinprotein interaction(PPI) network analysis. The expression levels of key genes were detected by quantitative realtime polymerase chain reaction(qRT-PCR). Results: After the investigation, 4 and 3 cases were respectively excluded from HQD and control groups because of the incomplete data. Additionally, 3 and 5 cases were lost to follow up in HQD and control groups, respectively. Finally, a total of 70 cases with good compliance were included for further DEGs analysis. A total of 1,070 DEGs(including 455 up-regulated genes and 615 down-regulated genes) in HQDG group and 227 DEGs(including 164 up-regulated genes and 63 down-regulated genes) in the control group were identified after treatment. Compared with the control group, 1,043 DEGs were specific in HQDG group. Besides, 1 up-regulated transcription factor(TF, such as GLI family zinc finger 1, GLI1) and 25 down-regulated TFs(such as drosophila mothers against decapentaplegic proteinfamily member 2, SMAD2) were identified. Pathway enrichment analysis showed that down-regulated Ras homolog gene family member A(RHOA) was enriched in pathogenic Escherichia coli infection. In the PPI network, up-regulated epidermal growth factor receptor(EGFR), and down-regulated cell division cycle 42(CDC42) as well as v-akt murine thymoma viral oncogene homolog 1(AKT1) had higher degrees. Moreover, long non-coding RNAs(lncR NA) growth arrest-specific 5(GAS5) was involved in the lncR NA-target regulatory network. Furthermore, qR T-PCR revealed that expression levels of CDC42 and GLI1 had significant differences in HQDG group before and after treatment(P<0.05). Conclusions: CDC42 and GLI1 may be the targets of HQDG in patients with hepatitis B cirrhosis. Additionally, SMAD2, EGFR, AKT1, RHOA and GAS5 might be associated with the curative effect of HQDG on hepatitis B cirrhosis patients.