GLIS Family Zinc Finger 1 was First Linked With Preaxial Polydactyly I in Humans by Stepwise Genetic Analysis

Background: Preaxial polydactyly (PPD) is one of the most common developmental malformations, with a prevalence of 0.8–1.4% in Asians. PPD is divided into four types, PPD I–IV, and PPD I is the most frequent type. Only six loci (GLI1, GLI3, STKLD1, ZRS, pre-ZRS, and a deletion located 240 kb from SHH) have been identified in non-syndromic PPD cases. However, pathogenesis of most PPD patients has never been investigated. This study aimed to understand the genetic mechanisms involved in the etiology of PPD I in a family with multiple affected members.Methods: We recruited a PPD I family (PPD001) and used stepwise genetic analysis to determine the genetic etiology. In addition, for functional validation of the identified GLIS1 variant, in vitro studies were conducted. GLIS1 variants were further screened in additional 155 PPD cases.Results: We identified a GLIS1 variant (NM_147193: c.1061G > A, p.R354H) in the PPD001 family. In vitro studies showed that this variant decreased the nuclear translocation of GLIS1 and resulted in increased cell viability and migration. RNA sequencing revealed abnormal TBX4 and SFRP2 expression in 293T cells transfected with mutant GLIS1. Additionally, we identified a GLIS1 variant (c.664G > A, p.D222N) in another PPD case.Conclusion: We identified two GLIS1 variants in PPD I patients and first linked GLIS1 with PPD I. Our findings contributed to future molecular and clinical diagnosis of PPD and deepened our knowledge of this disease.

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Essential Oil from Pinus Koraiensis Pinecones Inhibits Gastric Cancer Cells via the HIPPO/YAP Signaling Pathway

Molecules ◽

10.3390/molecules24213851 ◽

2019 ◽

Vol 24 (21) ◽

pp. 3851 ◽

Cited By ~ 5

Author(s):

Yandong Zhang ◽

Chao Xin ◽

Junqiang Qiu ◽

Zhenyu Wang

Keyword(s):

Essential Oil ◽

Signaling Pathway ◽

Rna Sequencing ◽

Gas Chromatography Mass Spectrometry ◽

Pinus Koraiensis ◽

Hippo Signaling ◽

Gastric Cancer Cells ◽

And Migration ◽

Anti Tumor Activity

Pinecone is a traditional folk herb, which has been used in China for many years. In this paper, the essential oil from Pinus koraiensis pinecones (PEO) was obtained by hydrodistillation and 41 compounds were identified by gas chromatography–mass spectrometry (GC-MS), mainly including α-Pinene (40.91%), Limonene (24.82%), and β-Pinene (7.04%). The purpose of this study was to investigate the anti-tumor activity of PEO on MGC-803 cells and its mechanism. Anti-tumor experiments in vitro showed PEO could significantly inhibit the proliferation and migration of MGC-803 cells, and it also could arrest the cell cycle in the G2/M phase, decrease the mitochondrial membrane potential, and induce apoptosis. Finally, the effects of PEO on genes expression on MGC-803 cells were analyzed by RNA sequencing, and results showed that after treatment with PEO, 100 genes were up-regulated, and 57 genes were down-regulated. According to the KEGG pathway and GSEA, FAT4, STK3, LATS2, YAP1, and AJUBA were down-regulated, which were related to HIPPO signaling pathway. Real-time PCR and western blot further confirmed the results of RNA sequencing. These results indicated that PEO may exert anti-tumor activity via the HIPPO/YAP signaling pathway. The anti-tumor mechanism of this oil can be further studied, which is important for the development of anti-tumor drugs.

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Histone deacetylase inhibitors reduce WB-F344 oval cell viability and migration capability by suppressing AKT/mTOR signaling in vitro

Archives of Biochemistry and Biophysics ◽

10.1016/j.abb.2015.11.004 ◽

2016 ◽

Vol 590 ◽

pp. 1-9 ◽

Cited By ~ 2

Author(s):

Peng Zhang ◽

Xiaofeng Zhu ◽

Ying Wu ◽

Ronglin Hu ◽

Dongming Li ◽

...

Keyword(s):

Cell Viability ◽

Histone Deacetylase ◽

Histone Deacetylase Inhibitors ◽

Mtor Signaling ◽

Oval Cell ◽

And Migration

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Antimicrobial ceragenins inhibit biofilms and affect mammalian cell viability and migration in vitro

FEBS Open Bio ◽

10.1002/2211-5463.12235 ◽

2017 ◽

Vol 7 (7) ◽

pp. 953-967 ◽

Cited By ~ 15

Author(s):

Melissa A. Olekson ◽

Tao You ◽

Paul B. Savage ◽

Kai P. Leung

Keyword(s):

Cell Viability ◽

Mammalian Cell ◽

And Migration

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Nanoparticles Loaded with the BET Inhibitor JQ1 Block the Growth of Triple Negative Breast Cancer Cells In Vitro and In Vivo

Cancers ◽

10.3390/cancers12010091 ◽

2019 ◽

Vol 12 (1) ◽

pp. 91 ◽

Cited By ~ 2

Author(s):

Valentina Maggisano ◽

Marilena Celano ◽

Rocco Malivindi ◽

Ines Barone ◽

Donato Cosco ◽

...

Keyword(s):

Breast Cancer ◽

Cell Viability ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Anticancer Efficacy ◽

Bet Inhibitor ◽

Physico Chemical ◽

And Migration

Inhibition of bromo-and extra-terminal domain (BET) proteins, epigenetic regulators of genes involved in cell viability, has been efficiently tested in preclinical models of triple negative breast cancer (TNBC). However, the use of the selective BET-inhibitor JQ1 on humans is limited by its very short half-life. Herein, we developed, characterized and tested a novel formulation of nanoparticles containing JQ1 (N-JQ1) against TNBC in vitro and in vivo. N-JQ1, prepared using the nanoprecipitation method of preformedpoly-lactid-co-glycolic acid in an aqueous solution containing JQ1 and poloxamer-188 as a stabilizer, presented a high physico-chemical stability. Treatment of MDA-MB 157 and MDA-MB 231 TNBC cells with N-JQ1 determined a significant decrease in cell viability, adhesion and migration. Intra-peritoneal administration (5 days/week for two weeks) of N-JQ1 in nude mice hosting a xenograft TNBC after flank injection of MDA-MB-231 cells determined a great reduction in the growth and vascularity of the neoplasm. Moreover, the treatment resulted in a minimal infiltration of nearby tissues. Finally, the encapsulation of JQ1 in nanoparticles improved the anticancer efficacy of this epigenetic compound against TNBC in vitro and in vivo, opening the way to test it in the treatment of TNBC.

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Effect of Glycosaminoglycan Replacement on Markers of Interstitial Cystitis In Vitro

Frontiers in Pharmacology ◽

10.3389/fphar.2020.575043 ◽

2020 ◽

Vol 11 ◽

Author(s):

Peadar Rooney ◽

Christina Ryan ◽

Barry J. McDermott ◽

Kapil Dev ◽

Abhay Pandit ◽

...

Keyword(s):

Cell Viability ◽

Interstitial Cystitis ◽

Pain Syndrome ◽

Bladder Pain Syndrome ◽

Receptor Expression ◽

Cell Growth And Migration ◽

Bladder Pain ◽

Inflammatory Models ◽

And Migration

Aims: To examine the effect of three commercial intravesical formulations of glycosaminoglycan on in vitro inflammatory models of IC/BPS to better understand there effect on specific markers of disease.Methods: Human urothelial cells (HTB-4) were cultured under four conditions in the presence or absence of commercial GAG formulations. Cells were cultured under a basal condition or pre-treated with protamine sulfate (100 ng/ml) (damages the endogenous glycosaminoglycan layer), hydrogen peroxide (1%) (a metabolic stressor) or TNFα (10 ng/ml) (creating an inflammatory environment). Each of these four culture conditions was then treated with one of three GAG formulations, CystistatⓇ, iAluRilⓇ and HyacystⓇ. Assays were then performed to examine the effect of the exogenous GAGs on cell viability, cell migration, sGAG production, cytokine and gene expression.Results: All GAG formulations were well tolerated by the HTB-4 cells and supported cell growth and migration. iAluRilⓇ was most effective at stimulating endogenous sGAG production under all conditions, increasing sGAGs by up to 15-fold. All GAG formulations significantly reduced the production of the pro-inflammatory cytokine IL-8 under basal conditions, while no GAG treatment suppressed cytokine production under any other condition. Only CystistatⓇ had a significant effect on HA receptor expression, significantly increasing ICAM-1 expression at 3 h that returned to basal levels at 24 h. No GAG treatment significantly changed the expression of GAG synthesis enzymes (CSGALNACT1, CSGALNACT2) or markers of tissue remodeling (MMP2, TIMP1) and pain (COX-1/PTGS-1, NGF).Conclusions: The data presented in this study reveal that commercial intravesical formulation support cell viability and migration. In addition, the commercial GAG formulations have a mild anti-inflammatory effect in the in vitro model of interstitial cystitis/bladder pain syndrome.

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Epidermal Growth Factor Promotes Proliferation and Migration of Follicular Outer Root Sheath Cells via Wnt/β-Catenin Signaling

Cellular Physiology and Biochemistry ◽

10.1159/000445630 ◽

2016 ◽

Vol 39 (1) ◽

pp. 360-370 ◽

Cited By ~ 15

Author(s):

Haihua Zhang ◽

Weixiao Nan ◽

Shiyong Wang ◽

Tietao Zhang ◽

Huazhe Si ◽

...

Keyword(s):

Egf Receptor ◽

Nuclear Translocation ◽

Hair Follicles ◽

Regulatory Genes ◽

Outer Root Sheath ◽

Daily Growth ◽

Root Sheath ◽

And Migration ◽

Proliferation And Migration

Background/Aims: To investigate the effect and molecular mechanism of EGF on the growth and migration of hair follicle outer root sheath (ORS) cells. Methods: Intact anagen hair follicles were isolated from mink skin and cultured with EGF in vitro to measure ORS daily growth. Meanwhile, purified primary ORS cells were treated or transfected with EGF, and their proliferation and migration were assessed by MTT assay and transwell assay, respectively. The signaling pathway downstream of EGF was characterized by using the Wnt/β-catenin signaling inhibitor, XAV-939. Results: EGF of 2-20 ng/ml, not higher or lower, promoted the growth of follicular ORS in vitro. EGF treatment or overexpression promoted the proliferation and migration of ORS cells. Moreover, EGF stimulation induced nuclear translocation of β-catenin, and upregulated the expression of Wnt10b, β-catenin, EGF receptor and SOX9. Inhibition of Wnt/β-catenin signaling by XAV-939 significantly reduced the basal and EGF-enhanced proliferation and migration of ORS cells. In addition, a number of follicle-regulatory genes, such as Survivin, Msx2 and SGK3, were upregulated by EGF in the ORS cells, which was also inhibited by XAV-939. Conclusion: EGF promotes the proliferation and migration of ORS cells and modulates the expression of several follicle-regulatory genes via Wnt/β-catenin signaling.

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Immune-modulating effects of alpha-1 antitrypsin

Biological Chemistry ◽

10.1515/hsz-2014-0161 ◽

2014 ◽

Vol 395 (10) ◽

pp. 1187-1193 ◽

Cited By ~ 56

Author(s):

Mario R. Ehlers

Keyword(s):

Nuclear Translocation ◽

Inflammatory Responses ◽

Graft Loss ◽

T Cell Subsets ◽

Intracellular Camp ◽

Alpha 1 Antitrypsin ◽

And Migration ◽

Pro Inflammatory Cytokines

Abstract Alpha-1 antitrypsin (AAT) is a circulating serine protease inhibitor (serpin) that inhibits neutrophil elastase in the lung, and AAT deficiency is associated with early-onset emphysema. AAT is also a liver-derived acute-phase protein that, in vitro and in vivo, reduces production of pro-inflammatory cytokines, inhibits apoptosis, blocks leukocyte degranulation and migration, and modulates local and systemic inflammatory responses. In monocytes, AAT has been shown to increase intracellular cAMP, regulate expression of CD14, and suppress NFκB nuclear translocation. These effects may be mediated by AAT’s serpin activity or by other protein-binding activities. In preclinical models of autoimmunity and transplantation, AAT therapy prevents or reverses autoimmune disease and graft loss, and these effects are accompanied by tolerogenic changes in cytokine and transcriptional profiles and T cell subsets. This review highlights advances in our understanding of the immune-modulating effects of AAT and their potential therapeutic utility.

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KCNQ1OT1 promotes the proliferation and migration of psoriatic keratinocytes by regulating miR-183-3p/GAB1

Allergologia et Immunopathologia ◽

10.15586/aei.v49i5.480 ◽

2021 ◽

Vol 49 (5) ◽

pp. 125-130

Author(s):

Ting Liu ◽

Xi Duan ◽

Jia He ◽

Chuan Yang

Keyword(s):

Cell Viability ◽

Cell Model ◽

Growth Factor Receptor ◽

Keratinocyte Proliferation ◽

Tnf Α ◽

Keratinocyte Cell Line Hacat ◽

Gated Channel ◽

And Migration ◽

Proliferation And Migration

Background: Differentially expressed lncRNAs have been reported to be involved in keratinocyte proliferation and migration, and participate in the development of psoriasis. Potassium voltage-gated channel subfamily Q member 1 overlapping transcript 1 (KCNQ1OT1) was implicated in the pathogenesis of various diseases, including cancer, sepsis, diabetic cardiomyopathy, and atherosclerosis. The influence of KCNQ1OT1 on proliferation and migration of psoriatic keratinocytes was unfolded in this study. Methods: Human keratinocyte cell line (HaCaT) was incubated with TNF-α to establish in vitro cell model of psoriasis. Cell viability and migration were assessed by MTT and wound healing, respectively. Target miRNA of KCNQ1OT1 was identified by luciferase activity and RNA immunoprecipitation (RIP) assays. Results: KCNQ1OT1 was up-regulated in TNF-α-induced HaCaT, and knockdown of KCNQ1OT1 reduced cell viability and suppressed migration of TNF-α-induced HaCaT. KCNQ1OT1 bind to miR-183-3p and negatively regulated expression of miR-183-3p. Over-expression of GAB1 (growth factor receptor binding 2-associated binding protein 1) counteracted with the suppressive effects of KCNQ1OT1 silence on cell viability and migration of TNF-α-induced HaCaT. Conclusion: Silence of KCNQ1OT1 suppressed proliferation and migration of TNF-α-induced HaCaT through regulation of miR-183-3p/GAB1, providing potential strategy for psoriasis.

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Carcinogenic effect of adenylosuccinate lyase (ADSL) in prostate cancer development and progression through the cell cycle pathway

Cancer Cell International ◽

10.1186/s12935-021-02174-6 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Jinling Liao ◽

Qiong Song ◽

Jie Li ◽

Kechen Du ◽

Yang Chen ◽

...

Keyword(s):

Prostate Cancer ◽

Cell Cycle ◽

Rna Sequencing ◽

Cancer Genomics ◽

Transcript Level ◽

Carcinogenic Effect ◽

Adenylosuccinate Lyase ◽

Cell Cycle Pathway ◽

And Migration

Abstract Background Prostate cancer (PCa) is still a serious male malignant disease across the world. However, no exact pathogenesis had been explained. Although adenylosuccinate lyase (ADSL) gene was identified to be important in PCa early in 1987, its comprehensive functions for PCa have not been presented. Methods The cBioPortal for Cancer Genomics, Oncomine and GEO database were retrieved to investigate the associations between of the ADSL gene and PCa. Then, the PC-3, DU145 and C4-2B cell lines were applied in vitro experiments. RNA sequencing and further western blot (WB) were applied to explore the potential mechanisms of ADSL gene in PCa. Results Based on PCa clinical datasets, we firstly found ADSL gene highly expressed in PCa tissues. Moreover, its transcript level increased in the metastatic PCa further. Elevated ADSL gene expression indicated a poor prognosis of PCa. While inhibiting the expression of ADSL with siRNA, the ability of cell proliferation and migration all declined markedly, with increased cell apoptosis inversely. Most of cells were blocked in the G0/G1 phase. Additionally, RNA sequencing also discovered the inactivity of cell cycle pathway after ADSL knockdown, which had also confirmed on the proteins levels. Conclusions Our study identified the ADSL as an oncogene of PCa through regulating the cell cycle pathway firstly, with explicit cell and clinical phenotypes. Further mechanisms were needed to confirm its carcinogenic effect.

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