MicroRNA-329-3p inhibits the Wnt/β-catenin pathway and proliferation of osteosarcoma cells by targeting transcription factor 7-like 1

An important factor in the emergence and progre sion of osteosarcoma(OS)is the dysregulated expression of microRNAs(miRNAs).Transcription factor 7-like 1(TCF7LI),a member of the T cell factor/lymphoid enhancer factor(TCF/LEF)transcription factor family,interacts with the Wnt signaling pathway regulator β-catenin and acts as a DNA-specific binding protein.This study sought to elucidate the impact of the interaction between miR 3293p and TCF7L1 on.the growth and apoptosis of OS and analyze the regulatory expression relationship between miRNA and mRNA in osteosarcoma cells using a variety of approaches.MiR329-3p was significantly downregulated,while TCF7L1 was considerably up-regulated in all examined OS cell lines.Additionally,a clinical comparison study was performed using the TCGA database.Subsequently,the regulatory relationship between miR-329-3p and TCF7L1 on the proliferation and apoptosis of OS cells was verified through in vitro and in vivo experiments.When miR 329-3p was transfected into the OS cell line,the expression of TCF7L1 decreased,the proliferation of OS cells was inhibited,the cytoskeleton disintegrated,and the nucleus condensed to fom apoptotic bodies.The expression of proteins that indicate apoptosis increased simultaneously.The cell cycle was arrested in the G0/G1 phase,and the G1/S transition was blocked.The introduction of miR 3293p also inhibited downstream Cyclin D1 of the Wnt pathway.Xenograf experiments indicated that the overexpression of miR-329-3p signi ficanly inhibited the growth of OS xenografts in nude mice,and the expression of TCF7L1 and C-Myc in tumor tssues decreased.MiR 329-3p was significantly reduced in OS cells and played a suppressive role in tumorigenesis and proliferation by targeting TCF7L1 both in vitro and in vivo.Osteosarcoma cell cycle arrest and pathway inhibition were observed upon the regulation of TCF7LI by miR 3293p.Summarizing these results,it can be inferred that miR.3293p exerts anticancer efects in osteosarcoma by inhibiting TCF7L1.

Effects of Wumen Gumi Bao Decoction on Ameliorating Bone Loss in Experimentally Induced Osteoporosis in Rats by Regulating Wnt3a/β-Catenin Pathway

[Objectives]To investigate the preventive effects of Wumen Gumi Bao Decoction(WMGBD)on estrogen deficiency-induced bone loss.[Methods]Three-month-old Sprague-Dawley rats were ovariectomized(OVX)and then treated with WMGBD,and their admixtures for six weeks.The bone trabecular microstructure,bone histopathological examination were determined in the rat femur tissue,and serum biomarkers of bone formation and resorption were analyzed by ELISA,and the protein expressions of Wnt3a,β-catenin,and phosphorylatedβ-catenin(p-β-catenin)were analyzed by Western blot.Statistical analysis was conducted by using one-way analysis of variance(ANOVA)followed by LSD post hoc analysis or independent samples t test using the scientific statistic software SPSS version 20.0.[Results]WMGBD could promote osteosis and ameliorate bone loss to improve the repair of cracked bone trabeculae of OVX rats.Furthermore,WMGBD also could prevent OVX-induced decrease in collagen fibers in the femoral tissue of ovariectomized rats and promote the regeneration of new bone or cartilage tissue,while WMGBD could activate the Wnt3a/β-catenin pathway.[Conclusions]WMGBD could ameliorate estrogen deficiency-induced bone loss via the regulation of Wnt3a/β-catenin pathway.

Inhibition of NF-kB and Wnt/β-catenin/GSK3p Signaling Pathways Ameliorates Cardiomyocyte Hypertrophy and Fibrosis in Streptozotocin (STZ)-induced Type 1 Diabetic Rats

Type 1 diabetes mellitus(T1DM)is associated with an increased risk of diabetic cardiomyopathy(DCM).Nuclear factor kappa B(NF-kB)and Wnt/β-catenin/GSK3p have been demonstrated to play pathogenic roles in diabetes.In this study,we evaluated the roles of these two pathways in T1 DM-induced cardiomyopathy in rats.Streptozotocin(STZ)-induced type 1 diabetic rats were treated with pyrrolidine dithiocarbamate(PDTC)or meisoindigo(Me)to inhibit NF-kB and Wnt/β-catenin/GSK3P respectively for 4 or 8 weeks.As compared with untreated diabetic rats,treatment with either PDTC or Me partly attenuated the myocardial hypertrophy and interstitial fibrosis,improved cardiac function,and exhibited reduction in inflammatory reaction.In addition,we found that inhibiting NF-κB and Wnt/β-catenin/GSK3β pathways could regulate glucose and lipid metabolism.The effects were associated with the decrease of NF-κB activity and the downregulation of some proinflammatory cytokines,including tumor necrosis factor-alpha(TNF-α)and interleukin(IL)-2.Our data suggested that the activities of NF-κB and Wnt/β-catenin/GSK3β pathways were both increased and inhibiting NF-κB and Wnt/β-catenin/GSK3β signaling pathways might improve myocardial injury in T1DM rats.

miR-544a对非小细胞肺癌细胞系Wnt信号通路抑制因子GSK3β表达的调控作用

目的探讨微小RNA-544a(miR-544a)对肺癌干细胞的自我更新能力影响及其可能的机制。方法通过生物信息学预测miR-544a的靶向基因,用荧光素酶报告系统及western blot验证其靶向关系;构建稳定表达miR-544a的非小细胞肺癌(NSCLC)细胞系95C和95D,并用荧光定量PCR验证;用肿瘤球悬浮培养实验检测miR-544a在形成肿瘤球中的作用。结果生物信息学预测发现,miR-544a可以靶向调节Wnt信号通路的抑制子GSK3β,并通过荧光素酶报告系统得到了验证(F=201.37,P<0.01);western blot结果显示,miR-544a可以下调GSK3β的表达,而β-catenin、CD133蛋白表达水平明显上调(F分别为7.73,3.37,9.43,P均<0.01);荧光定量PCR结果显示,95C、95D细胞在转染miR-544a后,miR-544a表达水平增高,分别为20.51±0.97、15.16±1.38(F=418.05,P<0.01)。肿瘤球悬浮培养实验发现,稳定表达miR-544a的细胞能够反复形成具有肿瘤干细胞特性的肿瘤球。结论 miR-544a可以通过直接下调GSK3β的表达来激活Wnt信号通路,以维持肺癌干细胞自我更新能力。

二氢丹参酮经GSK3β/Wnt途径调节膀胱癌T-24细胞增殖及侵袭的机制研究

目的:探讨二氢丹参酮经糖原合成酶激酶3β(GSK3β)/Wnt途径调节膀胱癌T-24细胞增殖及侵袭的机制。方法:体外培养膀胱癌T-24细胞,选择对数生长期细胞进行实验。实验分为对照组、阳性组、二氢丹参酮低、中、高剂量组。对照组不进行处理,阳性组给予终浓度为1mg·L^-1的吉西他滨,二氢丹参酮低、中、高剂量组分别给予终浓度为10,20,40 mg·L^-1的二氢丹参酮,继续培养24 h后检测细胞增殖率、细胞体外侵袭能力、细胞凋亡和细胞周期,用实时荧光定量PCR(RT-PCR)检测GSK3β、β-连环蛋白(β-catenin)、细胞周期蛋白D1(Cyclin D1)、E-钙黏蛋白(E-cadherin)和波形蛋白(Vimentin)mRNA表达。结果:与对照组比较,阳性组和二氢丹参酮各剂量组的T-24细胞增殖率、侵袭细胞数、β-catenin、Cyclin D1和Vimentin mRNA表达降低(P<0.05),细胞凋亡率、S期细胞数、GSK3β、E-cadherin mRNA表达增加(P<0.05),且二氢丹参酮各剂量组呈剂量依赖性,但效果不如阳性组(P<0.05)。结论:二氢丹参酮可以抑制膀胱癌T-24细胞增殖和侵袭,其机制可能与激活GSK3β/Wnt途径有关。

Wnt信号通路中β-catenin、GSK3β及Lef-1在卵巢癌中的表达及其意义

目的研究Wnt信号通路相关因子β-catenin、GSK3β及Lef-1在卵巢癌中的表达及意义。方法应用免疫组织化学En Vision法检测218例人卵巢组织(包括正常组织,卵巢良性腺瘤及腺癌组织标本)中β-catenin、GSK3β及Lef-1的表达情况。结果β-catenin、GSK3β及Lef-1在癌组织中的表达明显高于腺瘤及正常组织(P<0.05);β-catenin及Lef-1表达与淋巴结转移及FIGO分期有关(P<0.05),与肿瘤分级无关(P>0.05);GSK3β与肿瘤分级、淋巴结转移及FIGO分期有关(P<0.05);β-catenin、GSK3β及Lef-1三者在癌中的表达均与卵巢癌的类型无关(P>0.05)。β-catenin表达与GSK3β和Lef-1表达均呈正相关(P<0.05)。结论 Wnt信号通路中β-catenin、GSK3β及LEF-1在卵巢癌的发生发展过程中起了一定的作用,卵巢癌的进展可能和β-catenin分别与GSK3β及LEF-1共同作用促进细胞的增殖有关,三者高表达与卵巢癌的预后有关。

Down-regulation of mi R-30a-3p/5p promotes esophageal squamous cell carcinoma cell proliferation by activating the Wnt signaling pathway

AIM To investigate the potential role of micro RNA-30 a(mi R-30 a) in esophageal squamous cell carcinoma(ESCC).METHODS Expression of mi R-30 a-3 p/5 p was analyzed using microarray data and fresh ESCC tissue samples. Both in vitro and in vivo assays were used to investigate the effects of mi R-30 a-3 p/5 p on ESCC cell proliferation. Furthermore,Kyoto Encyclopedia of Genes and Genomes analysis was performed to explore underlying mechanisms involved in ESCC,and then,assays were carried out to verify the potential molecular mechanism of mi R-30 a in ESCC.RESULTS Low expression of mi R-30 a-3 p/5 p was closely associated with advanced ESCC progression and poor prognosis of patients with ESCC. Knock-down of mi R-30 a-3 p/5 p promoted ESCC cell proliferation. Increased mi R-30 a-3 p/5 p expression inhibited the Wnt signaling pathway by targeting Wnt2 and Fzd2.CONCLUSION Down-regulation of mi R-30 a-3 p/5 p promotes ESCC cell proliferation by activating the Wnt signaling pathway through inhibition of Wnt2 and Fzd2.

MiR-19a-3p regulates the Forkhead box F2-mediated Wnt/β-catenin signaling pathway and affects the biological functions of colorectal cancer cells

BACKGROUND Colorectal cancer(CRC)is one of the most common malignancies worldwide.AIM To explore the expression of microRNA miR-19a-3p and Forkhead box F2(FOXF2)in patients with CRC and the relevant mechanisms.METHODS Sixty-two CRC patients admitted to the hospital were enrolled into the study group,and sixty healthy people from the same period were assigned to the control group.Elbow venous blood was sampled from the patients and healthy individuals,and blood serum was saved for later analysis.MiR-19a-3p mimics,miR-19a-3p inhibitor,miR-negative control,small interfering-FOXF2,and short hairpin-FOXF2 were transfected into HT29 and HCT116 cells.Then quantitative polymerase chain reaction was performed to quantify the expression of miR-19a-3p and FOXF2 in HT29 and HCT116 cells,and western blot(WB)analysis was conducted to evaluate the levels of FOXF2,glycogen synthase kinase 3 beta(GSK-3β),phosphorylated GSK-3β(p-GSK-3β),β-catenin,p-β-catenin,α-catenin,Ncadherin,E-cadherin,and vimentin.The MTT,Transwell,and wound healing assays were applied to analyze cell proliferation,invasion,and migration,respectively,and the dual luciferase reporter assay was used to determine the correlation of miR-19a-3p with FOXF2.RESULTS The patients showed high serum levels of miR-19a-3p and low levels of FOXF2,and the area under the curves of miR-19a-3p and FOXF2 were larger than 0.8.MiR-19a-3p and FOXF2 were related to sex,tumor size,age,tumor-nodemetastasis staging,lymph node metastasis,and differentiation of CRC patients.Silencing of miR-19a-3p and overexpression of FOXF2 suppressed the epithelialmesenchymal transition,invasion,migration,and proliferation of cells.WB analysis revealed that silencing of miR-19a-3p and FOXF2 overexpression significantly suppressed the expression of p-GSK-3β,β-catenin,N-cadherin,and vimentin;and increased the levels of GSK-3β,p-β-catenin,α-catenin,and Ecadherin.The dual luciferase reporter assay confirmed that there was a targeted correlation of miR-19a-3p with FOXF2.In addition,a rescue experiment revealed that there were no differences in cell proliferation,invasion,and migration in HT29 and HCT116 cells co-transfected with miR-19a-3p-mimics+sh-FOXF2 and miR-19a-3p-inhibitor+si-FOXF2 compared to the miR-negative control group.CONCLUSION Inhibiting miR-19a-3p expression can upregulate the FOXF2-mediated Wnt/β-catenin signaling pathway,thereby affecting the epithelial-mesenchymal transition,proliferation,invasion,and migration of cells.Thus,miR-19a-3p is likely to be a therapeutic target in CRC.

RING finger and WD repeat domain 3 regulates proliferation and metastasis through the Wnt/β-catenin signalling pathways in hepatocellular carcinoma

BACKGROUND Hepatocellular carcinoma(HCC)exhibits high invasiveness and mortality rates,and the molecular mechanisms of HCC have gained increasing research interest.The abnormal DNA damage response has long been recognized as one of the important factors for tumor occurrence and development.Recent studies have shown the potential of the protein RING finger and WD repeat domain 3(RFWD3)that positively regulates p53 stability in response to DNA damage as a therapeutic target in cancers.AIM To investigate the relationship between HCC and RFWD3 in vitro and in vivo and explored the underlying molecular signalling transduction pathways.METHODS RFWD3 gene expression was analyzed in HCC tissues and adjacent normal tissues.Lentivirus was used to stably knockdown RFWD3 expression in HCC cell lines.After verifying the silencing efficiency,Celigo/cell cycle/apoptosis and MTT assays were used to evaluate cell proliferation and apoptosis.Subsequently,cell migration and invasion were assessed by wound healing and transwell assays.In addition,transduced cells were implanted subcutaneously and injected into the tail vein of nude mice to observe tumor growth and metastasis.Next,we used lentiviral-mediated rescue of RFWD3 shRNA to verify the phenotype.Finally,the microarray,ingenuity pathway analysis,and western blot analysis were used to analyze the regulatory network underlying HCC.RESULTS Compared with adjacent tissues,RFWD3 expression levels were significantly higher in clinical HCC tissues and correlated with tumor size and TNM stage(P<0.05),which indicated a poor prognosis state.RFWD3 silencing in BEL-7404 and HCC-LM3 cells increased apoptosis,decreased growth,and inhibited the migration in shRNAi cells compared with those in shCtrl cells(P<0.05).Furthermore,the in vitro results were supported by the findings of the in vivo experiments with the reduction of tumor cell invasion and migration.Moreover,the rescue of RFWD3 shRNAi resulted in the resumption of invasion and metastasis in HCC cell lines.Finally,gene expression profiling and subsequent experimental verification revealed that RFWD3 might influence the proliferation and metastasis of HCC via the Wnt/β-catenin signalling pathway.CONCLUSION We provide evidence for the expression and function of RFWD3 in HCC.RFWD3 affects the prognosis,proliferation,invasion,and metastasis of HCC by regulating the Wnt/β-catenin signalling pathway.

Wnt3a:functions and implications in cancer

Wnt3a,one of Wnt family members,plays key roles in regulating pleiotropic cellular functions,including self-renewal,proliferation,differentiation,and motility.Accumulating evidence has suggested that Wnt3 a promotes or suppresses tumor progression via the canonical Wnt signaling pathway depending on cancer type.In addition,the roles of Wnt3 a signaling can be inhibited by multiple proteins or chemicals.Herein,we summarize the latest findings on Wnt3 a as an important therapeutic target in cancer.

Neuroprotective effect of rapamycin on spinal cord injury via activation of the Wnt/β-catenin signaling pathway

The Wnt/β-catenin signaling pathway plays a crucial role in neural development, axonal guid- ance, neuropathic pain remission and neuronal survival. In this study, we initially examined the effect of rapamycin on the Wnt/β-catenin signaling pathway after spinal cord iniury, by intraperitoneally injecting spinal cord injured rats with rapamycin over 2 days. Western blot analysis and immunofluorescence staining were used to detect the expression levels of β-catenin protein, caspase-3 protein and brain-derived neurotrophic factor protein, components of the Wnt/β-catenin signaling pathway. Rapamycin increased the levels of β-catenin and brain-derived neurotrophic factor in the injured spinal cord, improved the pathological morphology at the injury site, reduced the loss of motor neurons, and promoted motor functional recovery in rats after spinal cord injury. Our experimental fndings suggest that the neuroprotective effect of rapamycin intervention is mediated through activation of the Wnt/β-catenin signaling pathway after spinal cord injury.

Involvement of the Wnt signaling pathway and cell apoptosis in the rat hippocampus following cerebral ischemia/reperfusion injury

We investigated the role of the Wnt signaling pathway in cerebral ischemia/reperfusion injury by examining β-catenin and glycogen synthase kinase-3β protein expression in the rat hippocampal CA1 region following acute cerebral ischemia/reperfusion. Our results demonstrate that cell apoptosis increases in the CA1 region following ischemia/reperfusion. In addition, β-catenin and glycogen synthase kinase-3β protein expression gradually increases, peaking at 48 hours following reperfusion. Dickkopf-1 administration, after cerebral ischemia/reperfusion injury, results in decreased cell apoptosis, and β-catenin and glycogen synthase kinase-3β expression, in the CA1 region. This suggests that β-catenin and glycogen synthase kinase-3β, both components of the Wnt signaling pathway, participate in cell apoptosis following cerebral ischemia/reperfusion injury.

Role of Wnt/β-catenin Signaling Pathway in the Mechanism of Calcification of Aortic Valve

Aortic valve calcification is a common disease in the elderly, but its cellular and molecular mechanisms are not clear. In order to verify the hypothesis that Wnt/β-catenin signaling pathway is involved in the process of calcification of aortic valve, porcine aortic valve interstitial cells（VICs） were isolated, cultured and stimulated with oxidized low density lipoprotein（ox-LDL） for 48 h to induce the differentiation of VICs into osteoblast-like cells. The key proteins and genes of Wnt/β-catenin signaling pathway, such as glycogen synthase kinase 3β（GSK-3β） and β-catenin, were detected by using Western blotting and real-time polymerase chain reaction（PCR）. The results showed that the VICs managed to differentiate into osteoblast-like cells after the stimulation with ox-LDL and the levels of proteins and genes of GSK-3β and β-catenin were increased significantly in VICs after stimulation for 48 h（P0.05）. It is suggested that Wnt/β-catenin signaling pathway may play a key role in the differentiation of VICs into osteoblast-like cells and make great contribution to aortic valve calcification.

糖尿病溃疡中Wnt/β-catenin信号通路表达的变化

目的:观察糖尿病(DM)溃疡中Wnt/β-catenin信号通路表达的变化,探讨该信号通路在糖尿病难愈性溃疡中的作用。方法:雌性Wistar大鼠采用高脂高糖饲料联合小剂量链脲佐菌素液腹腔注射法制备糖尿病模型。分别取正常对照组与DM组制作溃疡模型。观察创面造模后第3天、第7天和第14天对照组及DM组创面愈合情况的变化,并采用HE染色法检测创面组织形态结构的变化,采用ELISA法和RT-PCR法检测创面组织中β-catenin、GSK-3β和Rspo-3蛋白及mRNA的变化。结果:DM组大鼠的创面愈合率明显低于对照组(P<0.05),且与对照组相比,其创面组织中含有较少的炎性细胞、纤维母细胞及新生毛细血管。DM组大鼠创面组织中β-catenin和Rspo-3蛋白及mRNA的表达水平均低于对照组,GSK-3β蛋白及mRNA的表达水平均高于对照组(P<0.05)。结论:Wnt/β-catenin通路的下调有可能导致了糖尿病溃疡的难愈,而该通路的下调可能源自于Rspo-3蛋白表达的下降。

Wnt信号通路在有氧运动改善高脂饮食诱导C57BL/6小鼠胰岛素抵抗中的作用

目的:探讨有氧运动对C57BL/6小鼠骨骼肌Wnt信号通路的关键蛋白糖原合成激酶(GSK3β)磷酸化表达水平及其下游信号蛋白分子连环蛋白(β-catenin)磷酸化水平的影响及其与胰岛素抵抗(IR)的关系。方法:将4周龄雄性C57BL/6小鼠随机分为正常对照组(Con组)和胰岛素抵抗模型组(IR组),分别喂饲标准饲料和高脂饲料10周。建立IR模型后,再将IR组随机分为高脂饮食安静组(HC组)和高脂饮食运动组(HE组);Con组随机分为正常饮食安静组(NC)和正常饮食运动组(NE),随后运动组小鼠进行持续6周、75%VO2max强度的有氧跑台运动。6周训练结束后24小时,分别检测小鼠口服糖耐量试验(OGTT)和空腹血清胰岛素值(FINs);采用苏木精-伊红(HE)染色观察小鼠胰腺组织胰岛β细胞形态学变化;采用Realtime PCR及Western Blot方法检测小鼠骨骼肌GSK3β和β-catenin基因及蛋白表达。结果:(1)与NC组相比,HC组小鼠OGTT、FINs及胰岛β细胞形态学结果呈现IR的病理生理学变化,而6周有氧跑台运动(HE vs HC)可以显著改善OGTT、FINs及胰岛形态学变化;(2)与NC组相比,HC组骨骼肌组织GSK3βm RNA表达及p GSK3βSer9蛋白表达分别下降60%及1.19%(P<0.05)。β-catenin m RNA和pβ-catenin Ser33/37Thr41蛋白表达分别增加60%和19.23%(P<0.05);(3)与NC组相比,NE组骨骼肌组织GSK3βm RNA表达和GSK3β蛋白表达分别增加40.00%(P<0.05)和36.11%,β-catenin m RNA表达降低15.00%(P<0.05)。结论:6周有氧运动可显著改善高脂饮食诱导小鼠IR,其机制与Wnt信号通路活性变化相关。

多功能的蛋白:糖原合成酶激酶-3

糖原合成酶激酶-3(GSK-3)是一个多功能的丝氨酸/苏氨酸类激酶,在真核生物中普遍存在。在哺乳动物中包括两个亚型,即GSK-3a和GSK-3b。GSK-3至少在三条细胞通路上有作用:Wnt/wingless,PI3-kinase以及Hedgehog信号通路,该酶的作用主要包括调节糖原的合成代谢,参与细胞的分化与增殖等。研究发现,GSK-3在某些疾病,如阿尔茨海默病和非胰岛素依赖型糖尿病(NIDDM)中,其活性会异常升高。现已发现了几种针对该酶的抑制剂,如aloisine,paullones和马来酰胺类化合物等。这些抑制剂的确在分子水平特异性地抑制GSK-3的活性,而对其他激酶几乎没有作用。关于这些抑制剂的研究工作也已经在细胞水平和动物模型上开展起来,为开发以GSK-3为靶点的新的治疗药物创造了良好的基础。

Wnt信号分子在大鼠中枢神经系统的表达及其共存

目的：通过研究Wnt信号分子在大鼠中枢神经系统（CNS）的表达及分布,以探讨Wnt信号分子在CNS早期发育的可能调控机制,以及Wnt信号分子之间的功能联系.方法：应用免疫组织化学及双标记技术,观察了Wnt信号分子β-catenin、糖原合成酶激酶3β（Gsk-3β）、大肠腺瘤样息肉基因（APC）等关键调控分子在成年大鼠CNS的表达分布、细胞定位及共存关系.结果：免疫组织化学显色显示Gsk-3β阳性细胞多为具有突起的神经元样细胞,其主要分布区域包括新皮层、背内侧丘脑、海马、小脑浦肯野细胞及脑干多个核团.β-catenin与APC在分布模式上与Gsk-3β高度一致.双标记实验显示β-catenin与APC除神经元外,在部分星形胶质细胞也存在表达,而Gsk-3β则主要显示神经元定位.部分β-catenin阳性细胞,特别是室下层及海马区阳性细胞还呈现与神经前体细胞标记物巢蛋白的共存.结论：Wnt信号分子在CNS存在着密切相关的功能联系,同时在不同细胞及组织区域可能还具有其特有的生物效应,与神经前体细胞和神经胶质细胞增殖分化密切相关,对其相关信号机制有待深入研究.

Targeting key signalling pathways in oesophageal adenocarcinoma:A reality for personalised medicine?

Cancer treatments are rapidly changing.Curative treatment for oesophageal adenocarcinoma currently involves surgery and cytotoxic chemotherapy or chemoradiotherapy.Outcomes for both regimes are generally poor as a result of tumor recurrence.We have reviewed the key signalling pathways associated with oesophageal adenocarcinomas and discussed the recent trials of novel agents that attempt to target these pathways.There are many trials underway with the aim of improving survival in oesophageal cancer.Currently,phase 2 and 3 trials are focused on MAP kinase inhibition,either through inhibition of growth factor receptors or signal transducer proteins.In order to avoid tumor resistance,it appears to be clear that targeted therapy will be needed to combat the multiple signalling pathways that are in operation in oesophageal adenocarcinomas.This may be achievable in the future with the advent of gene signatures and a combinatorial approach.

Expression of hepatic Wnt5a and its clinicopathological features in patients with hepatocellular carcinoma

Backgroud： Wingless-type MMTV integration site family member 5a （Wnt5a） is involved in carcinogenesis.However, little data are available in Wnt5a signaling with hepatocellular carcinoma （HCC）. In thepresent study, we investigated the expression of hepatic Wnt5a in HCC and the role of Wnt5a in HCCprogression and outcome.

miR-103-3p targets Ndel1 to regulate neural stem cell proliferation and differentiation

The regulation of adult neural stem cells(NSCs) is critical for lifelong neurogenesis. MicroRNAs(miRNAs) are a type of small, endogenous RNAs that regulate gene expression post-transcriptionally and influence signaling networks responsible for several cellular processes. In this study, mi R-103-3 p was transfected into neural stem cells derived from embryonic hippocampal neural stem cells. The results showed that mi R-103-3 p suppressed neural stem cell proliferation and differentiation, and promoted apoptosis. In addition, mi R-103-3 p negatively regulated Nud E neurodevelopment protein 1-like 1(Ndel1) expression by binding to the 3′ untranslated region of Ndel1. Transduction of neural stem cells with a lentiviral vector overexpressing Ndel1 significantly increased cell proliferation and differentiation, decreased neural stem cell apoptosis, and decreased protein expression levels of Wnt3 a, β-catenin, phosphor-GSK-3β, LEF1, c-myc, c-Jun, and cyclin D1, all members of the Wnt/β-catenin signaling pathway. These findings suggest that Ndel1 is a novel mi R-103-3 p target and that mi R-103-3 p acts by suppressing neural stem cell proliferation and promoting apoptosis and differentiation. This study was approved by the Animal Ethics Committee of Nantong University, China(approval No. 20200826-003) on August 26, 2020.