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1.
Aging (Albany NY) ; 14(15): 6316-6337, 2022 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-35963646

RESUMO

Serum amyloid A-like 1 (SAAL1) was recently identified as a novel oncogene in hepatocellular carcinoma (HCC). To explore the potential role of SAAL1 in other cancers, we conducted a pan-cancer analysis of SAAL1 expression and its association with tumor microenvironment (TME) immunological profiles, sensitivity to chemotherapy agents, response to immunotherapy, and patient prognosis. SAAL1 was overexpressed in most malignant tumors in association with poor prognosis. Moreover, its expression was positively correlated with TME-relevant immune and mismatch signatures, immunostimulatory infiltrating cells (CD4+ memory T cells, activated NK cells, M1 macrophages, and cytotoxic CD8+ T cells), microsatellite instability (MSI), tumor mutational burden (TMB), neoantigen load, and immune checkpoint markers (PD-L1, LAG-3 and CTLA-4) in multiple cancers. SAAL1 overexpression was also associated with immunotherapy response and overall survival (OS) in bladder cancer (BLCA) patients who had received anti-PD-L1 treatment. Gene set enrichment analysis (GSEA) further showed significant enrichment of SAAL1 in immune cell signaling, cell cycle, and cell adhesion pathways. Moreover, we detected tumor-specific correlations between SAAL1 expression and either chemoresistance or sensitivity to common chemotherapeutics. Lastly, we showed that SAAL1 silencing suppresses both malignant phenotype and expression of PD-L1 in lung cancer A549 cells in vitro. These findings suggest that SAAL1 contributes to tumorigenesis and antitumor immunity mechanisms in different cancer types, and may thus serve as both a prognostic biomarker and potential target for cancer immunotherapy.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Biomarcadores Tumorais/metabolismo , Linfócitos T CD8-Positivos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Humanos , Imunoterapia , Neoplasias Hepáticas/genética , Oncogenes , Prognóstico , Microambiente Tumoral/genética
2.
Int J Oncol ; 61(1)2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35583005

RESUMO

Recent studies have indicated that mineral dust­induced gene (MDIG) is an oncogene induced by environmental factors, which has a key role in the development and progression of various tumor types, through epigenetic modifications; however, there are no previous pan­cancer analyses of MDIG. In the present study, a comprehensive pan­cancer analysis of MDIG was performed using public databases. The results demonstrated that MDIG was upregulated in tumor tissue samples compared with normal tissue, that it was present in all cancer cell lines and it was closely associated with the prognosis of patients with different tumor types. Furthermore, MDIG expression was closely associated with the immunological characteristics of the tumor microenvironment (TME), such as the frequency of tumor­infiltrating immune cells, TME­relevant signatures, immunostimulatory genes, immune checkpoint genes, chemokine receptor genes, tumor mutational burden and microsatellite instability. In parallel, high expression of MDIG was associated with improved overall survival of patients and this was verified in a cohort of patients who had received anti­programmed cell death 1 ligand 1 treatment. Furthermore, high expression of MDIG led to multiple drug resistance in The Cancer Genome Atlas­lung adenocarcinoma cohort. In addition, gene set variant analysis and gene set enrichment analysis indicated that MDIG was involved in cell cycle regulation. In vitro experiments suggested that MDIG promoted cell proliferation through the mTOR complex 2/Akt and pyruvate dehydrogenase kinase 1/Akt signaling pathways. In summary, the present study suggests that MDIG may be a prognostic biomarker and therapeutic target for various cancer types.


Assuntos
Dioxigenases/metabolismo , Histona Desmetilases/metabolismo , Neoplasias Pulmonares , Proteínas Nucleares/metabolismo , Oncogenes , Biomarcadores Tumorais/genética , Dioxigenases/genética , Humanos , Ácidos Cetoglutáricos , Neoplasias Pulmonares/genética , Proteínas Nucleares/genética , Oxigenases/metabolismo , Prognóstico , Proteínas Proto-Oncogênicas c-akt/genética , Microambiente Tumoral/genética
3.
Oncol Rep ; 45(5)2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33760153

RESUMO

Mineral dust­induced gene (mdig) is a novel lung cancer­related oncogene. The aim of this study was to explore the effects of mdig on angiogenesis and lymphangiogenesis by vascular endothelial growth factor (VEGF) in lung adenocarcinoma. mdig­overexpressing A549, H1299 and 293T cells, mdig­silenced A549, human umbilical vein endothelial cells (HUVECs) and human lymphatic endothelial cells (HLECs) were cultured under normoxic and hypoxic conditions. Protein expression levels of mdig, epidermal growth factor receptor (EGFR), phospho(p)­EGFR Tyr1068, hypoxia­inducible factor­1α (HIF­1α), VEGF­A/C/D and VEGF­R1/R2/R3 were assessed using western blotting. mRNA expression levels of mdig, EGFR and HIF­1α were measured using RT­qPCR. Tube formation and xenograft tumor experiments were performed to examine the mechanism of mdig in angiogenesis and lymphangiogenesis. Protein expression levels of EGFR, HIF­1α and VEGF­A/C/D were significantly upregulated in cells cultured under hypoxic conditions compared with those cultured under normoxic conditions, whereas the levels of mdig were decreased. Protein expression levels of EGFR, p­EGFR and VEGF­A/R1/R2 were significantly increased in the mdig­overexpressing cells, whereas the levels of HIF­1α and VEGF­C/D/R3 were decreased compared with those in control cells, all of which were reversed in mdig­silenced cells. Tumor volumes and density of angiogenesis in the mdig­overexpressing group were significantly increased compared with those in the control group, whereas the density of lymphangiogenesis was decreased. No tumors formed in the mdig­silenced group after 3 weeks of assessment in vivo. Protein expression levels of EGFR, p­EGFR, VEGF­A and angiogenesis density were significantly reduced in the mdig­overexpressing cells treated with an EGFR inhibitor, whereas the levels of HIF­1α, VEGF­C/D and the lymphangiogenesis density were significantly increased in mdig­overexpressing cells treated with a HIF­1α agonist. All changes in protein expression were reversed in EGFR agonist and HIF­1α inhibitor treated mdig­silenced cells. In conclusion, mdig is an oxygen­sensitive protein that promotes tumor growth and angiogenesis by activating the EGFR/p­EGFR/VEGF­A/VEGF­R1/R2 pathway and inhibits lymphangiogenesis by blocking the HIF­1α/VEGF­C/D/VEGF­R3 pathway.


Assuntos
Adenocarcinoma de Pulmão/patologia , Dioxigenases/metabolismo , Histona Desmetilases/metabolismo , Neoplasias Pulmonares/patologia , Linfangiogênese/genética , Neovascularização Patológica/genética , Proteínas Nucleares/metabolismo , Adenocarcinoma de Pulmão/irrigação sanguínea , Adenocarcinoma de Pulmão/genética , Animais , Linhagem Celular Tumoral , Desmetilação do DNA , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HEK293 , Histonas/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/agonistas , Subunidade alfa do Fator 1 Induzível por Hipóxia/antagonistas & inibidores , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Pulmão/irrigação sanguínea , Pulmão/patologia , Neoplasias Pulmonares/irrigação sanguínea , Neoplasias Pulmonares/genética , Linfangiogênese/efeitos dos fármacos , Camundongos , Neovascularização Patológica/induzido quimicamente , Neovascularização Patológica/patologia , Transdução de Sinais/genética , Carga Tumoral , Hipóxia Tumoral/genética , Regulação para Cima , Fatores de Crescimento do Endotélio Vascular/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
4.
Oncol Lett ; 18(4): 4294-4307, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31579066

RESUMO

Mineral dust-induced gene (MDIG) is a proto- oncogene associated with lung cancer that serves a key role in the biological processes of tumorigenesis. The aim of the present study was to determine whether MDIG is involved in cisplatin (DDP) resistance in lung adenocarcinoma, and to investigate the associated molecular mechanism. In the present study, MDIG-knockdown and MDIG-overexpressing A549 cells and DDP-resistant A549/DDP cells were initially constructed, and then the mRNA and protein expression levels of MDIG and ATP-binding cassette (ABC) transporters (ABCB1, ABCC1, ABCG2), and the expression levels of the major associated proteins in the WNT/ß-catenin pathway were determined by reverse transcription-quantitative PCR and Western blotting experiments. The results revealed that the mRNA and protein expression levels of MDIG in A549/DDP cells were significantly higher compared with those in A549 cells, and that the protein expression levels of MDIG increased in a dose-dependent manner with increasing DDP concentrations. Overexpression of MDIG in A549 and A549/DDP cells led to an increase in the IC50 value, whereas silencing of MDIG led to a clear reduction in the IC50 value. The overexpression of MDIG in the A549 and A549/DDP cells markedly upregulated the mRNA and protein expression levels of ABCB1, ABCC1, ABCG2, WNT family member 5A, WNT family member 3A and active ß-catenin, and these were markedly decreased following MDIG silencing. Taken together, these results demonstrated that the DDP resistance of lung adenocarcinoma may be associated with an upregulation of MDIG expression, and that the expression levels of MDIG are positively associated with the degree of DDP resistance. Furthermore, MDIG promoted the expression of ABC transporters in tumor cells by activating the WNT/ß-catenin signaling pathway, which may, in turn, lead to DDP resistance in lung adenocarcinoma.

5.
Wei Sheng Wu Xue Bao ; 56(11): 1776-85, 2016 Nov 04.
Artigo em Chinês | MEDLINE | ID: mdl-29741841

RESUMO

Objective: To analyze adenovirus-mediated endosome lysis of T cells, we developed a novel approach based on pHrodo dextran (pH-sensitive fluorescent dye). Methods: After incubating Jurkat cells (T cell leukemia) with serotype 5 adenovirus (Ad5) and pHrodo dextran, we determined the optimal incubation time and concentration of pHrodo dextran. To assess viral lysis of the endosome, we monitored the ratio changes of mean fluorescence intensity in different time points by laser scanning confocal microscopy. Results: After incubating Jurkat cells with Ad5 and 80 µg/mL pHrodo dextran for 10 minutes, we observed the fluorescence intensity was significantly reduced at 30 minutes compared with that of endosomes at 0 minute. However, we found the mean fluorescence intensity was only slightly reduced by inhibiting V-ATPase with the bafilomycin A1 treatment. Conclusion: The method based on pH-sensitive dye can be used to analyze the adenovirus-mediated endosome lysis of T cells.


Assuntos
Adenoviridae/fisiologia , Endossomos/química , Microscopia Confocal/métodos , Linfócitos T/química , Adenoviridae/genética , Linhagem Celular , Endossomos/virologia , Fluorescência , Corantes Fluorescentes/química , Humanos , Concentração de Íons de Hidrogênio , Linfócitos T/virologia
6.
J Colloid Interface Sci ; 455: 125-33, 2015 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-26057945

RESUMO

A novel ionic liquid modified copolymer hydrogel (PAMDA) was successfully synthesized by a simple water solution copolymerization using acrylamide (AM), dimethyldiallylammonium chloride (DADMAC) and ionic liquid (1-allyl-3-methylimidazolium chloride; [Amim]Cl) as copolymerization monomers. The structure and morphology of as-prepared copolymer hydrogel PAMDA were confirmed by Fourier transform infrared (FT-IR), field-emission scanning electron microscope (FE-SEM) and thermogravimetric analysis (TG). The copolymer hydrogel was applied as a novel adsorbent for the rapid removal of Cr (VI) from aqueous solution. The effects of several parameters such as the content of ionic liquid [Amim]Cl, solution pH, contact time, adsorbent dosage and initial Cr (VI) concentration on the adsorption were also investigated. The modification of [Amim]Cl significantly enhanced Cr (VI) adsorption. The adsorption equilibrium data fitted with Langmuir isotherm model better than Freundlich isotherm model. The maximum adsorption capacity for Cr (VI) ions was 74.5 mg L(-1) at 323 K based on Langmuir isotherm model. The removal rate could reach 95.9% within 10 min at 323 K and the adsorption process of Cr (VI) on PAMDA was well described by the pseudo-second-order kinetic model. The activation energy of adsorption was further investigated and found to be 1.094 kJ mol(-1), indicating the adsorption of Cr (VI) onto PAMDA was physisorption.

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