scholarly journals Bioinformatic Prediction of Signaling Pathways for Apurinic/Apyrimidinic Endodeoxyribonuclease 1 (APEX1) and Its Role in Cholangiocarcinoma Cells

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2587
Author(s):  
Doungdean Tummanatsakun ◽  
Tanakorn Proungvitaya ◽  
Sittiruk Roytrakul ◽  
Siriporn Proungvitaya
Keyword(s):  
Protein Expression ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Tumor Metastasis ◽  
Poor Survival ◽  
Interactive Analysis ◽  
Damage Repair ◽  
Son Of Sevenless ◽  
Human Protein Atlas ◽  
Related Proteins

Apurinic/apyrimidinic endodeoxyribonuclease 1 (APEX1) is involved in the DNA damage repair pathways and associates with the metastasis of several human cancers. However, the signaling pathway of APEX1 in cholangiocarcinoma (CCA) has never been reported. In this study, to predict the signaling pathways of APEX1 and related proteins and their functions, the effects of APEX1 gene silencing on APEX1 and related protein expression in CCA cell lines were investigated using mass spectrometry and bioinformatics tools. Bioinformatic analyses predicted that APEX1 might interact with cell division cycle 42 (CDC42) and son of sevenless homolog 1 (SOS1), which are involved in tumor metastasis. RNA and protein expression levels of APEX1 and its related proteins, retrieved from the Gene Expression Profiling Interactive Analysis (GEPIA) and the Human Protein Atlas databases, revealed that their expressions were higher in CCA than in the normal group. Moreover, higher levels of APEX1 expression and its related proteins were correlated with shorter survival time. In conclusion, the signaling pathway of APEX1 in metastasis might be mediated via CDC42 and SOS1. Furthermore, expression of APEX1 and related proteins is able to predict poor survival of CCA patients.

scholarly journals Genetic Polymorphism in Extracellular Regulators of Wnt Signaling Pathway

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Garima Sharma ◽  
Ashish Ranjan Sharma ◽  
Eun-Min Seo ◽  
Ju-Suk Nam
Keyword(s):  
Genetic Polymorphism ◽  
Wnt Signaling ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Wnt Signaling Pathway ◽  
The Other ◽  
Present Review ◽  
Receptor Complex ◽  
Related Proteins ◽  
Related Association

The Wnt signaling pathway is mediated by a family of secreted glycoproteins through canonical and noncanonical mechanism. The signaling pathways are regulated by various modulators, which are classified into two classes on the basis of their interaction with either Wnt or its receptors. Secreted frizzled-related proteins (sFRPs) are the member of class that binds to Wnt protein and antagonizes Wnt signaling pathway. The other class consists of Dickkopf (DKK) proteins family that binds to Wnt receptor complex. The present review discusses the disease related association of various polymorphisms in Wnt signaling modulators. Furthermore, this review also highlights that some of the sFRPs and DKKs are unable to act as an antagonist for Wnt signaling pathway and thus their function needs to be explored more extensively.

scholarly journals Notch Signaling Pathway Is Activated by Sulfate Reducing Bacteria

2021 ◽  
Vol 11 ◽  
Author(s):  
Sudha B. Singh ◽  
Cristina N. Coffman ◽  
Amanda Carroll-Portillo ◽  
Matthew G. Varga ◽  
Henry C. Lin
Keyword(s):  
Protein Expression ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Notch Pathway ◽  
Sulfate Reducing Bacteria ◽  
Notch Signaling Pathway ◽  
Sulfate Reducing ◽  
Inflammatory Conditions ◽  
Related Proteins ◽  
Reducing Bacteria

Sulfate Reducing Bacteria (SRB), usually rare residents of the gut, are often found in increased numbers (called a SRB bloom) in inflammatory conditions such as Inflammatory Bowel Disease (IBD), pouchitis, and periodontitis. However, the underlying mechanisms of this association remain largely unknown. Notch signaling, a conserved cell-cell communication pathway, is usually involved in tissue development and differentiation. Dysregulated Notch signaling is observed in inflammatory conditions such as IBD. Lipolysaccharide and pathogens also activate Notch pathway in macrophages. In this study, we tested whether Desulfovibrio, the most dominant SRB genus in the gut, may activate Notch signaling. RAW 264.7 macrophages were infected with Desulfovibrio vulgaris (DSV) and analyzed for the expression of Notch signaling pathway-related proteins. We found that DSV induced protein expression of Notch1 receptor, Notch intracellular domain (NICD) and p21, a downstream Notch target, in a dose-and time-dependent manner. DSV also induced the expression of pro-IL1β, a precursor of IL-1β, and SOCS3, a regulator of cytokine signaling. The gamma secretase inhibitor DAPT or Notch siRNA dampened DSV-induced Notch-related protein expression as well the expression of pro-IL1β and SOCS3. Induction of Notch-related proteins by DSV was not affected by TLR4 -IN -C34(C34), a TLR4 receptor antagonist. Additionally, cell-free supernatant of DSV-infected macrophages induced NICD expression in uninfected macrophages. DSV also activated Notch pathway in the human epithelial cell line HCT116 and in mouse small intestine. Thus, our study uncovers a novel mechanism by which SRB interact with host cells by activating Notch signaling pathway. Our study lays a framework for examining whether the Notch pathway induced by SRB contributes to inflammation in conditions associated with SRB bloom and whether it can be targeted as a therapeutic approach to treat these conditions.

scholarly journals FTO demethylates m6A modifications in HOXB13 mRNA and promotes endometrial cancer metastasis by activating the WNT signaling pathway

2020 ◽  
Author(s):  
Lin Zhang ◽  
Yicong Wan ◽  
Zihan Zhang ◽  
Yi Jiang ◽  
Jinghe Lang ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Protein Expression ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Tumor Metastasis ◽  
Cancer Metastasis ◽  
Wnt Signaling Pathway ◽  
Luciferase Reporter ◽  
Cell Metastasis

Abstract Background Abnormal FTO expression causes faulty m6A modifications in mRNA and affects tumor progression. However, the expression and function of FTO in endometrial cancer (EC) and the genes regulated by FTO remain unclear.Methods qPCR detected the FTO expression level in EC tissues, and IHC staining determined the FTO protein expression in tissue arrays. FTO was stably overexpressed or knocked down in EC cell lines by lentiviruses. The biological roles of FTO in cancer cell metastasis and invasion were evaluated by wound-healing, Transwell assays and mouse intra-abdominal implantation models. mRNA-seq, RIP-seq, and MeRIP-seq were combined to comprehensively map the genes regulated by FTO. RNA pull-down, dual-luciferase reporter and RNA stability experiments confirmed that YTHDF2 regulates the metabolism of HOXB13 mRNA via m6A. Western blot analysis confirmed that HOXB13 regulates EC cell metastasis and invasion through the WNT signaling pathway.Results FTO is more highly expressed in metastatic EC and can promote tumor metastasis and invasion in vivo and in vitro. By removing the m6A modification in the 3'UTR region of HOXB13, FTO abolishes m6A recognition by YTHDF2 and promotes the stability of HOXB13 mRNA and protein expression. High HOXB13 expression activates the WNT signaling pathway, promotes c-myc, snail, MMP2, MMP7, and MMP9 expression, and inhibits E-cadherin expression, leading to tumor metastasis and invasion.Conclusions FTO promotes HOXB13 expression through m6A, activates the WNT signaling pathway, and promotes EC invasion and metastasis. FTO is a new potential target for the treatment of tumor metastasis.

scholarly journals Yi-Qi-Ping-Chuan-Fang Reduces TSLP Elevation Caused by LPS + Poly(I:C) via Inhibiting TLR4/MYD88/NF-κB Signaling Pathway

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Minye Qu ◽  
Xiang Tao ◽  
Jian Ma
Keyword(s):  
Signaling Pathways ◽  
Signaling Pathway ◽  
Primary Response ◽  
Poly I:C ◽  
Myeloid Differentiation ◽  
Bronchial Epithelial ◽  
Chinese Medicine Formula ◽  
Primary Response Gene ◽  
Protein Expressions ◽  
Related Proteins

Objective. To explore the correlation between Thymic Stromal Lymphopoietin (TSLP) and the Nuclear Factor- (NF-) κB signaling pathways in bronchial epithelial cells and to clarify whether the traditional Chinese medicine formula Yi-Qi-Ping-Chuan-Fang (YQPC) reduces inflammation by inhibiting TSLP/NF-κB signaling pathways. Methods. Cells were stimulated with LPS + Poly(I:C) and treated with YQPC. The expressions of TSLP and NF-κB signaling pathways related proteins P65, IκK, IκBa, P-P65, P-IκK, P-IκBa were detected. The effects of NF-κB upstream molecules, Toll-like receptors 3 and 4, myeloid differentiation primary response gene 88 (Myd88), TIR-domain-containing adapter-inducing interferon-β (TRIF), and downstream inflammatory cytokines, TNF-α, IL-1β, IL-6, and IL-8, were assessed. Results. The mRNA and protein expressions of TSLP were significantly increased after LPS + Poly(I:C) stimulation, the total protein IκBa and IκK decreased (P < 0.05), and the phosphorylated protein P-P65, P-IκK, and P-IκBα increased. After YQPC treatment, the expression of TSLP, P-P65, P-IκBa, and P-IκK was significantly inhibited (P < 0.05). The activation of TLR4 and MyD88 decreased, and release of IL-1β, IL-6, IL-8, and TNF-α reduced (P < 0.05). Conclusion. In summary, the expression of TSLP is activated by the NF-κB signaling pathway. YQPC alleviated inflammation by inhibiting TSLP through regulating the NF-κB activation and translocation.

Calmodulin and son of sevenless dependent signaling pathways regulate midline crossing of axons in the Drosophila CNS

Development ◽  
2000 ◽  
Vol 127 (9) ◽  
pp. 1991-2000 ◽  
Author(s):  
J.L. Fritz ◽  
M.F. Van Berkum
Keyword(s):  
Signaling Pathways ◽  
Signaling Pathway ◽  
Intracellular Signaling ◽  
Genetic Approach ◽  
Intracellular Signaling Pathways ◽  
Midline Crossing ◽  
Son Of Sevenless

The establishment of axon trajectories is ultimately determined by the integration of intracellular signaling pathways. Here, a genetic approach in Drosophila has demonstrated that both Calmodulin and Son of sevenless signaling pathways are used to regulate which axons cross the midline. A loss in either signaling pathway leads to abnormal projection of axons across the midline and these increase with roundabout or slit mutations. When both Calmodulin and Son of sevenless are disrupted, the midline crossing of axons mimics that seen in roundabout mutants, although Roundabout remains expressed on crossing axons. Calmodulin and Son of sevenless also regulate axon crossing in a commissureless mutant. These data suggest that Calmodulin and Son of sevenless signaling pathways function to interpret midline repulsive cues which prevent axons crossing the midline.

Targeted Delivery of Natural Bioactives and Lipid-nanocargos against Signaling Pathways Involved in Skin Cancer

2020 ◽  
Vol 27 ◽  
Author(s):  
Mohammad Kashif Iqubal ◽  
Aiswarya Chaudhuri ◽  
Ashif Iqubal ◽  
Sadaf Saleem ◽  
Madan Mohan Gupta ◽  
...  
Keyword(s):  
Skin Cancer ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Targeted Delivery ◽  
Skin Pigmentation ◽  
Wnt Signaling Pathway ◽  
Human Beings ◽  
Radiation Chemical ◽  
Cell Leukemia Virus Type ◽  
Human T Cell

: At present, skin cancer is a widespread malignancy in human beings. Among diverse population types, Caucasian populations are much more prone in comparison to darker skin populations due to the comparative lack of skin pigmentation. Skin cancer is divided into malignant and non-melanoma skin cancer, which is additionally categorized as basal and squamous cell carcinoma. The exposure to ultraviolet radiation, chemical carcinogen (polycyclic aromatic hydrocarbons, arsenic, tar, etc.), and viruses (herpes virus, human papillomavirus, and human T-cell leukemia virus type-1) are major contributing factors of skin cancer. There are distinct pathways available through which skin cancer develops, such as the JAKSTAT pathway, Akt pathway, MAPKs signaling pathway, Wnt signaling pathway, to name a few. Currently, several targeted treatments are available, such as monoclonal antibodies, which have dramatically changed the line of treatment of this disease but possess major therapeutic limitations. Thus, recently many phytochemicals have been evaluated either alone or in combination with the existing synthetic drugs to overcome their limitations and have found to play a promising role in the prevention and treatment. In this review, complete tracery of skin cancer, starting from the signaling pathways involved, newer developed drugs with their targets and limitations along with the emerging role of natural products alone or in combination as potent anticancer agents and their molecular mechanism involved has been discussed. Apart from this, various nanocargos have also been mentioned here, which can play a significant role in the management and treatment of different types of skin cancer.

Biological role of AKT, and regulation of AKT signaling pathway by thymoquinone: perspectives in cancer therapeutics

2020 ◽  
Vol 20 ◽  
Author(s):  
Md. Junaid ◽  
Yeasmin Akter ◽  
Syeda Samira Afrose ◽  
Mousumi Tania ◽  
Md. Asaduzzaman Khan
Keyword(s):  
Clinical Trials ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Inhibitory Effect ◽  
Akt Signaling ◽  
Review Article ◽  
Therapeutic Drug ◽  
Akt Signaling Pathway ◽  
Anti Cancer

Background: AKT/PKB is an important enzyme with numerous biological functions, and its overexpression is related to the carcinogenesis. AKT stimulates different signaling pathways that are downstream of activated tyrosine kinases and phosphatidylinositol 3-kinase, hence functions as an important target for anti-cancer drugs. Objective: In this review article, we have interpreted the role of AKT signaling pathways in cancer and natural inhibitory effect of Thymoquinone (TQ) in AKT and its possible mechanism. Method: We have collected the updated information and data on AKT, their role in cancer and inhibitory effect of TQ in AKT signaling pathway from google scholar, PubMed, Web of Science, Elsevier, Scopus and many more. Results: There are many drugs already developed, which can target AKT, but very few among them have passed clinical trials. TQ is a natural compound, mainly found in black cumin, which has been found to have potential anti-cancer activities. TQ targets numerous signaling pathways, including AKT, in different cancers. In fact, many studies revealed that AKT is one of the major targets of TQ. The preclinical success of TQ suggests its clinical studies on cancer. Conclusion: This review article summarizes the role of AKT in carcinogenesis, its potent inhibitors in clinical trials, and how TQ acts as an inhibitor of AKT and TQ’s future as a cancer therapeutic drug.

Mass Spectrometry-based Label-free Quantitative Proteomic Analysis of CCl4-induced Acute Liver Injury in Mice Intervened by Total Glycosides from Ligustri Lucidi Fructus

2020 ◽  
Vol 17 ◽  
Author(s):  
Qian Lu ◽  
Hai-Zhu Xing ◽  
Nian-Yun Yang
Keyword(s):  
Insulin Resistance ◽  
Liver Injury ◽  
Protein Expression ◽  
Signaling Pathway ◽  
Proteomic Analysis ◽  
Acute Liver Injury ◽  
Liver Cells ◽  
Differentially Expressed ◽  
Liver Protein ◽  
Differentially Expressed Proteins

Background: CCl4 acute liver injury (ALI) is a classical model for experimental research. However, there are few reports involved in the fundamental research of CCl4-induced ALI Ligustri Lucidi Fructus (LLF) are and its prescription have been used to treat hepatitis illness clinically. LLF and its active ingredients displayed anti-hepatitis effects, but the mechanism of function has not been fully clarified Objective: To investigate the proteomic analysis of CCl4-induced ALI, and examine the effects of active total glycosides (TG) from LLF on ALI of mice4, including histopathological survey and proteomic changes of liver tissues, and delineate the possible underlying mechanism. Methods: CCl4 was used to produce ALI mice model. The model mice were intragastrically administrated with TG and the liver his-topathological changes of mice were examined. At the end of test, mice liver samples were collected, after protein denaturation, re-duction, desalination and enzymatic hydrolysis, identification was carried out by nano LC-ESI-OrbiTrap MS/MS technology. The data was processed by Maxquant software. The differentially-expressed proteins were screened and identified, and their biological information was also analyzed based on GO and KEGG analysis. Key protein expression was validated by Western blot analysis Results: A total of 705 differentially-expressed proteins were identified during the normal, model and administration group. 9 signifi-cant differential proteins were focused based on analysis. Liver protein expression changes of CCl4-induced ALI mice were mainly involved in several important signal channels, namely FoxO signaling pathway, autophagy-animal, insulin signaling pathway. TG has anti-liver damnification effect in ALI mice, the mechanism of which is related to FoxO1 and autophagy pathways Conclusion: CCl4 inhibited expression of insulin-Like growth factor 1 (Igf1) and 3-phosphoinositide-dependent protein kinase 1 (Pdpk1) in liver cells and induced insulin resistance, thus interfered with mitochondrial autophagy and regeneration of liver cells and the metabolism of glucose and lipid, and caused hepatic necrosis in mice. TG resisted liver injury in mice. TG adjusted the expression level of key proteins Igf1 and Pdpk1 after liver injury and improved insulin resistance, thus promoted autophagy and resisted the liver damage

scholarly journals CHN1 promotes epithelial–mesenchymal transition via the Akt/GSK-3β/Snail pathway in cervical carcinoma

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Haoqi Zhao ◽  
Lan Wang ◽  
Shufang Wang ◽  
Xihua Chen ◽  
Min Liang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Lymph Node ◽  
Signaling Pathway ◽  
Cervical Carcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Xenograft Tumor ◽  
Mesenchymal Transition ◽  
Gsk 3Β ◽  
Related Proteins

Abstract Background Metastasis and invasion are crucial in determining the mortality of cervical carcinoma (CC) patients. The epithelial–mesenchymal transition (EMT) is now a universal explanation for the mechanisms of tumor metastasis. Α-chimeric protein (α-chimaerin, CHN1) plays an important role in the regulation of signal transduction and development. However, the molecular regulatory relationships between CHN1 and CC progression in relation to EMT have not yet been identified. Methods The expression of CHN1 in CC tissues, adjacent tissues, and lymph node metastases from CC patients was detected by immunohistochemistry. Upregulation and knockdown of CHN1 were achieved by transfection of CC cells. The effect of CHN1 on cell proliferation was determined by CCK-8 and plate clone formation assays. Changes in migration and invasion capabilities were evaluated using scratch migration and transwell invasion assays. The effect of CHN1 overexpression and interference on xenograft tumor growth was determined by tumor weight and pathological analyses. The expression of EMT-related mRNAs was measured by qRT-PCR in transfected CC cells. EMT-related proteins and Akt/GSK-3β/Snail signaling pathway-related proteins were also evaluated by western blotting. Results CHN1 was overexpressed in CC tissues and was associated with lymph node metastasis and low survival in CC patients. Overexpression of CHN1 promoted cell proliferation, migration, and invasion in CC cells. In contrast, silencing of CHN1 inhibited these phenomena. Overexpression of CHN1 promoted tumor formation in an in vivo xenograft tumor mouse model, with increased tumor volumes and weights. In addition, CHN1 induced the expression of EMT-related transcription factors, accompanied by the decreased expression of epithelial markers and increased expression of mesenchymal markers. The Akt/GSK-3β/Snail signaling pathway was activated by overexpression of CHN1 in vitro, and activation of this pathway was inhibited by the signaling pathway inhibitor LY294002. Conclusion These results suggest that CHN1 promotes the development and progression of cervical carcinoma via the Akt/GSK-3β/Snail pathway by inducing EMT.

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