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β-catenin Deletion in Regional Neural Progenitors Leads to Congenital Hydrocephalus in Mice

Neuroscience Bulletin 2022年第1期38卷 81-94页

作者： Lin Ma Yanhua Du Xiangjie Xu Hexi Feng Yi Hui Nan Li Guanyu Jiang Xiaoqing Zhang Xiaocui Li Ling Liu Translational Medical Center for Stem Cell Therapy Shanghai East HospitalSchool of MedicineTongji UniversityShanghai200120China Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of the Ministry of Education Orthopaedic Department of Tongji HospitalShanghai200065China Brain and Spinal Cord Innovative Research Center School of MedicineTongji UniversityShanghai200092China Key Laboratory of Neuroregeneration of Shanghai Universities School of MedicineTongji UniversityShanghai200092China Tsingtao Advanced Research Institute Tongji UniversityQingdao266071China Shanghai Institute of Stem Cell Research and Clinical Translation Shanghai200120China Department of Pathology and Pathophysiology School of MedicineTongji UniversityShanghai200092China Department of Immunology and Microbiology Shanghai Institute of ImmunologyShanghai Jiao Tong University School of MedicineShanghai200025China Shanghai First Maternity and Infant Hospital School of MedicineTongji UniversityShanghai200092China

Congenital hydrocephalus is a major neurological disorder with high rates of morbidity and mortality;however,the underlying cellular and molecular mechanisms remain largely *** animal models mirroring both embryonic and postnatal hydrocephalus are also ***,we describe a new mouse model of congenital hydrocephalus through knockout ofβ-catenin in Nkx2.1-expressing regional neural *** ventriculomegaly and an enlarged brain were consistently observed in knockout mice from embryonic day 12.5 through to *** profiling revealed severe dysfunctions in progenitor maintenance in the ventricular zone and therefore in cilium biogenesis afterβ-catenin *** analyses also revealed an aberrant neuronal layout in both the ventral and dorsal telencephalon in hydrocephalic mice at both embryonic and postnatal ***,knockout ofβ-catenin in regional neural progenitors leads to congenital hydrocephalus and provides a reproducible animal model for studying pathological changes and developing therapeutic interventions for this devastating disease.

关键词： Congenital hydrocephalus β-catenin Ependymal cells Nkx2.1 Neural development

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ATP-citrate lyase regulates stemness and metastasis in hepatocellular carcinoma via the Wnt/β-catenin signaling pathway

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Hepatobiliary & Pancreatic Diseases International 2021年第3期20卷 251-261页

作者： Qin Han Ci-An Chen Wen Yang Dong Liang Hong-Wei Lv Gui-Shuai Lv Qian-Ni Zong Hong-Yang Wang International Co-operation Laboratory on Signal Transduction Eastern Hepatobiliary Surgery HospitalSecond Military Medical UniversityShanghai 200438China National Center for Liver Cancer Research Shanghai 200000China Mengchao Hepatobiliary Hospital of Fujian Medical University Fuzhou 350108China State Key Laboratory of Oncogenes and Related Genes Shanghai Cancer InstituteRenji HospitalShanghai Jiao Tong UniversityShanghai 200032China

Background: Hepatocellular carcinoma(HCC) is one of the most highly malignant tumors. Liver tumor-initiating cells(LTICs) have been considered to contribute to HCC progression and metastasis. ATP-citrate lyase(ACLY), as a key enzyme for de novo lipogenesis, has been reported to be upregulated in various tumors. However, its expression and role in HCC and LTICs remain unknown. Methods: The expressions of ACLY in HCC tissues were detected by quantitative real-time PCR(q RT-PCR), Western blotting and immunohistochemistry. Kaplan-Meier curves and Chi-square test were used to determine the clinical significance of ACLY expression in HCC patients. A series of assays were performed to determine the function of ACLY on stemness, migration and invasion of HCC cells. Luciferase reporter assay, Western blotting and immunoprecipitation were used to study the regulation of the Wnt/β-catenin signaling by ACLY. Rescue experiments were performed to investigate whether β-catenin was the mediator of ACLY-regulated stemness and migration in HCC cells. Results: ACLY was highly expressed in HCC tissues and LTICs. Overexpression of ACLY was significantly correlated with poor prognosis, progression and metastasis of HCC patients. Knockdown of ACLY remarkably suppressed stemness properties, migration and invasion in HCC cells. Mechanistically, ACLY could regulate the canonical Wnt pathway by affecting the stability of β-catenin, and Lys49 acetylation of β-catenin might mediate ACLY-regulated β-catenin level in HCC cells. Conclusions: ACLY is a potent regulator of Wnt/β-catenin signaling in modulating LTICs stemness and metastasis in HCC. ACLY may serve as a new target for the diagnosis and treatment of HCC.

关键词： Hepatocellular carcinoma ATP-citrate lyase Liver tumor-initiating cells Metastasis β-catenin

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Sijunzi Decoction Inhibits Stemness by Suppressingβ-catenin Transcriptional Activity in Gastric Cancer Cells

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Chinese Journal of Integrative Medicine 2022年第8期28卷 702-710页

作者： LI Yue-jun LIAO Lin-li LIU Pei TANG Ping WANG Hong PENG Qing-hua Department of Oncology the Third Affiliated Hospital of Hunan University of Chinese MedicineZhuzhou412000Hunan ProvinceChina Department of Oncology the First Affiliated Hospital of Hunan College of Traditional Chinese MedicineZhuzhou412000Hunan ProvinceChina Hunan Provincial Key Laboratory for the Prevention and Treatment of Ophthalmology and Otolaryngology Diseases with Traditional Chinese Medicine Hunan University of Chinese MedicineChangsha410208China

Objective:To investigate a previously uncharacterized function of Sijunzi Decoction(SJZD)in inhibition of gastric cancer stem cells(GCSCs).Methods:MKN74 and MKN45,two CD44 positive gastric cancer cell lines with stem cell properties were *** cells were divided into 2 *** group was treated with SJZD(1-5 mg/mL)for indicated time(48 h-14 days).The control group was treated with equal volume of phosphate buffered *** Counting Assay Kit-8 were used to measure cell *** colony formation and GCSCs marker expression were performed to determine GCSCs *** fractionation and chromatin immunoprecipitation assays were used to assess the distribution and DNA-binding activity of β-catenin after SJZD treatment,***:SJZD treatment repressed cell growth and induced apoptosis in MKN74 and MKN45 cell lines(Pβ-catenin(Pβ-catenin.

关键词： Sijunzi Decoction Chinese medicine gastric cancer cancer stem cells β-catenin

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Suppression of GSK3β by ERK mediates lipopolysaccharide induced cell migration in macrophage through β-catenin signaling

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Protein & Cell 2012年第10期3卷 762-768页

作者： Kai Gong Fangfang Zhou Huizhe Huang Yandao Gong Long Zhang Department of Biological Sciences and Biotechnology Tsinghua UniversityBeijing 100084China Leiden University Medical Center Department of Molecular Cell BiologyLeidenthe Netherland Faculty of Basic Medical Sciences Chongqing Medical UniversityChongqing 400016China

We investigate the role of β-catenin signaling in the response of macrophage to lipopolysaccharide(LPS)using RAW264.7 *** rapidly stimulated cytosolic β-catenin accumulation.β-catenin-mediated transcription was showed to be required for LPS induced gene expression and cell ***,ERK activation-primed GSK3β inactivation by Akt was demonstrated to mediate the LPS induced β-catenin ***,our findings suggest that suppression of GSK3β by ERK stimulatesβ-catenin signaling therefore contributes to LPS induced cell migration in macrophage activation.

关键词： LPS ERK GSK3β β-catenin cell migration

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TRAIL and Celastrol Combinational Treatment Suppresses Proliferation, Migration, and Invasion of Human Glioblastoma Cells via Targeting Wnt/β-catenin Signaling Pathway

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Chinese Journal of Integrative Medicine 2024年第4期30卷 322-329页

作者： QIN Jing-jing NIU Meng-da CHA Zhe GENG Qing-hua LI Yu-lin REN Chun-guang David P.Molloy YU Hua-rong Research Center of Neuroscience School of Basic Medical SciencesChongqing Medical UniversityChongqing(400016)China Laboratory of Developmental Biology Department of Cell Biology and GeneticsSchool of Basic Medical SciencesChongqing Medical UniversityChongqing(400016)China Department of Biochemistry and Molecular Biology School of Basic Medical SciencesChongqing Medical UniversityChongqing(400016)China

Objective To investigate the mechanistic basis for the anti-proliferation and anti-invasion effect of tumor necrosis factor-related apoptosis-induced ligand(TRAIL)and celastrol combination treatment(TCCT)in glioblastoma *** Cell counting kit-8 was used to detect the effects of different concentrations of celastrol(0-16µmol/L)and TRAIL(0-500 ng/mL)on the cell viability of glioblastoma cells.U87 cells were randomly divided into 4 groups,namely control,TRAIL(TRAIL 100 ng/mL),Cel(celastrol 0.5µmol/L)and TCCT(TRAIL 100 ng/mL+celastrol 0.5µmol/L).Cell proliferation,migration,and invasion were detected by colony formation,wound healing,and Transwell assays,*** reverse transcription polymerase chain reaction and Western blotting were performed to assess the levels of epithelial-mesenchymal transition(EMT)markers(zona occludens,N-cadherin,vimentin,zinc finger E-box-binding homeobox,Slug,and β-catenin).Wnt pathway was activated by lithium chloride(LiCl,20 mol/L)and the mechanism for action of TCCT was *** Celastrol and TRAIL synergistically inhibited the proliferation,migration,invasion,and EMT of U87 cells(Pβ-catenin and its associated proteins(Pβ-catenin and its downstream genes,as well as the migration and invasion of glioblastoma cells(Pβ-catenin *** underlies a novel mechanism of action for TCCT as an effective therapy for glioblastoma.

关键词： celastrol Chinese medicine tumor necrosis factor-related apoptosis-induced ligand glioblastoma β-catenin Tripterygium wilfordii

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Activation of the wnt/β-catenin/CYP1B1 pathway alleviates oxidative stress and protects the blood-brain barrier under cerebral ischemia/reperfusion conditions

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Neural Regeneration Research 2024年第7期19卷 1541-1547页

作者： Xingyong Chen Nannan Yao Yanguang Mao Dongyun Xiao Yiyi Huang Xu Zhang Yinzhou Wang Department of Neurology Fujian Provincial HospitalShengli Clinical Medical College of Fujian Medical UniversityFuzhouFujian ProvinceChina Department of Neurology Cangzhou Central HospitalCangzhouHebei ProvinceChina Fujian Academy of Medical Science FuzhouFujian ProvinceChina Key Testing Laboratory of Fujian Province FuzhouFujian ProvinceChina

Accumulating evidence suggests that oxidative stress and the Wnt/β-catenin pathway participate in stroke-induced disruption of the blood-brain ***,the potential links between them following ischemic stroke remain largely *** present study found that cerebral ischemia leads to oxidative stress and repression of the Wnt/β-catenin ***,Wnt/β-catenin pathway activation by the pharmacological inhibito r,TWS119,relieved oxidative stress,increased the levels of cytochrome P4501B1(CYP1B1)and tight junction-associated proteins(zonula occludens-1[ZO-1],occludin and claudin-5),as well as brain microvascular density in cerebral ischemia *** r,rat brain microvascular endothelial cells that underwent oxygen glucose deprivation/reoxygenation displayed intense oxidative stress,suppression of the Wnt/β-catenin pathway,aggravated cell apoptosis,downregulated CYP1B1and tight junction protein levels,and inhibited cell prolife ration and *** ofβ-catenin or knockdown ofβ-catenin and CYP1B1 genes in rat brain mic rovascular endothelial cells at least partly ameliorated or exacerbated these effects,*** addition,small interfering RNA-mediatedβ-catenin silencing decreased CYP1B1 expression,whereas CYP1B1 knoc kdown did not change the levels of glycogen synthase kinase 3β,Wnt-3a,andβ-catenin proteins in rat brain microvascular endothelial cells after oxygen glucose deprivatio n/***,the data suggest that CYP1B1 can be regulated by Wnt/β-catenin signaling,and activation of the Wnt/β-catenin/CYP1B1 pathway contributes to alleviation of oxidative stress,increased tight junction levels,and protection of the blood-brain barrier against ischemia/hypoxia-induced injury.

关键词： blood-brain barrier CYP1B1 oxidative stress oxygen glucose deprivation/reoxygenation tight junction vascular endothelial cells Wnt/β-catenin pathway β-catenin

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Hoxc13/β-catenin Correlation with Hair Follicle Activity in Cashmere Goat

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Journal of Integrative Agriculture 2012年第7期11卷 1159-1166页

作者： WU Jiang-hong ZHANG Yan-jun ZHANG Jia-xin CHANG Zi-li LI Jin-quan YAN Zu-wei Husile ZHANG Wen-guang Key Laboratory of Animal Genetics Breeding and Reproduction Inner Mongolian Autonomous Region Hohhot 010018 P.R.China College of Animal Science Inner Mongolia Agricultural University Hohhot 010018 P.R.China College of Science Inner Mongolia Agricultural University Huhhot 010018 P.R.China

Seasonal hair follicle activity and fibre growth in some Cashmere-bearing goats （Caprus hircus） is a cyclic process that is well characterized morphologically but understood incompletely at the molecular level. As an initial step in discovering regulators in hair-follicle activity and cycling, we used qPCR to investigate 19 genes expression in Cashmere goat side skin from 12 mon. Many of these genes may be associated with the hair follicle development-relevant genes （HFDRGs） in the literature. Here we show that Hoxc13/β-catenin gene associated with the follicle activity. In addition, Hoxc13 was found to be expressed with an drastic increase between July and November for melatonin treatments. To further investigate the role of Hoxcl3 on HFDRGs, fibroblasts and keratinocytes from Cashmere goat skin were transfected with p-ECFP- Hoxc13. The result suggested that overexpression ofHoxcl3 gene decreased HFDRGs with negative role for hair follicle development and increase HFDRGs with positive role for hair follicle development in vitro. These findings provide data on the Hoxc13 expression profile of normal Cashmere goat skin and Cashmere goat skin with melatonin treatment, and demonstrate hair-follicle-activity dependent regulation of Hoxc13 expression.

关键词： Hoxcl3 β-catenin Cashmere goat hair follicle activity cycle

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ShRNA-mediated gene silencing of β-catenin inhibits growth of human colon cancer cells

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World Journal of Gastroenterology 2007年第48期13卷 6581-6587页

作者： Wen-Sheng Huang Jian-Ping Wang Ting Wang Jie-Yu Fang Ping Lan Jin-Ping Ma Surgery Department The First Affiliated Hospital Sun Yat-sen University Guangzhou 510080 Guangdong Province China

AIM: To observe the gene silencing mediated by the specific shRNA targeted against β-catenin and its effect on cell proliferation and cycle distribution in the human colon cancer cell line Colo205. METHODS: Two shRNA plasmid vectors against β-catenin were constructed and transfected into Colo205 cells with LipofectamineTM2000. The down-regulations of β-catenin, c-myc and cyclinD1 expressions were detected by RT-PCR and western blot analysis. The cell proliferation inhibitions were determined by MTT assay and soft agar colony formation assay. The effect of these two β-catenin shRNAs on cell cycle distribution and apoptosis was examined by flow cytometry. RESULTS: These two shRNA vectors targeted against β-catenin efficiently suppressed the expression of β-catenin and its down stream genes, c-myc and cyclinD1. The expression inhibition rates were around 40%-50% either at the mRNA or at the protein level. The shRNA-mediated gene silencing of β-catenin resulted in significant inhibition of cell growth both on the culture plates and in the soft agar. Moreover, the cancer cells showed significant G0/G1 arrest and increased apoptosis at 72 h post transfection due to gene silencing. CONCLUSION: These specific shRNAs targeted against β-catenin could have a gene silencing effect and block the WNT signaling pathway. They could inhibit cell growth, increase apoptosis, and induce cell cycle arrest in Colo205 cells. ShRNA interference against β-catenin is of potential value in gene therapy of colon cancer.

关键词： β-catenin RNA interference Apoptosis Colon cancer WNT

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Comparison of gene expression of the oncogenic Wnt/β-catenin signaling pathway components in the mouse and human epididymis

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Asian Journal of Andrology 2015年第6期17卷 1006-1011,I0011页

作者： Kai Wang Ning Li Ching-Hei Yeung Trevor G Cooper Xue-Xia Liu Juan Liu Wen-Ting Wang Yan Li Hui Shi Fu-Jun Liu School of Agriculture Ludong University Yantai Shandong China Central Laboratory Yantai Yuhuangding Hospital Yantai Shandong China College of Life Science Yantai University Yantai Shandong China

β-catenin is an integral part of the Wnt signaling pathway and has been linked to tumorigenesis and multiple developmental processes. The high β-catenin expression with low tumor incidence in the human epididymis is thus intriguing. In the present study, the β-catenin gene and protein was found to be highly expressed in the murine caput epididymidis, and the protein mainly localized along the lateral plasma membranes of adjacent epithelial cells throughout both human and mouse epididymides. Furthermore, the adult mouse epididymis was found to express almost all the Wnt/β-catenin signaling pathway genes that were determined previously by our group in the human organ. Despite the differences in epididymal structure, the similar location of β-catenin and the high concordance of this pathway＇s components＇ gene expression in both the adult human and mouse epididymides make the mouse a suitable animal model for studying the anti-tumor mechanism of the epididymis. In addition, both the mRNA and protein expression of β-catenin shared a similar spatial expression as the mRNA of Rosl, a proto-oncogene and a key developmental regulator of the initial segment of the mouse epididymis. The observations on the parallel temporal expression of β-catenin and Rosl during postnatal development raise the possibility that the canonical Writ signaling pathway has an additional role in the postnatal development of mouse epididymis.

关键词： epididymis postnatal development tumorigenesis Wnt/β-catenin pathway β-catenin

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KIF18B promotes tumor progression in osteosarcoma by activating β-catenin

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Cancer Biology & Medicine 2020年第2期17卷 371-386页

作者： Tian Gao Ling Yu Zhiwei Fang Jiayong Liu Chujie Bai Shu Li Ruifeng Xue Lu Zhang Zhichao Tan Zhengfu Fan Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of Bone and Soft Tissue TumorPeking University Cancer Hospital&InstituteBeijing 100142China Department of Orthopedics Renmin Hospital of Wuhan UniversityWuhan 430060China

Objective:Osteosarcoma is a common primary highly malignant bone *** family member 18B(K1F18B)has been identified as a potential oncogene involved in the development and metastasis of several cancer *** KIF18B overexpression in osteosarcoma tissue is clearly detected,its specific function in the disease process remains to be ***:K IF18B expression was assessed in osteosarcoma tissues and *** additionally evaluated the effects of KIF18B on proliferation,migration,and invasion of osteosarcoma cells,both in vitro and in ***:Our results showed overexpression of KIF18B in osteosarcoma tissues and *** of K IF18B induced G1/S phase arrest and significantly inhibited proliferation,migration,and invasion of osteosarcoma cells,both in vitro and in vivo.K IF18B regulated P-catenin expression at the transcriptional level by controlling nuclear aggregation of ATF2 and at the post-transcriptional level by interacting with the adenomatous polyposis coli(APC)tumor suppressor gene in osteosarcoma ***:KIF18B plays a carcinogenic role in osteosarcoma by regulating expression ofβ-catenin transcriptionally via decreasing nuclear aggregation of ATF2 or post-transcriptionally through interactions with *** collective findings support the potential utility of KIF18B as a novel prognostic biomarker for osteosarcoma.

关键词： β-catenin APC ATF2 KIF18B osteosarcoma

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