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1.
Aging (Albany NY) ; 12(1): 156-177, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31896739

RESUMO

A promising new strategy for cancer therapy is to target the autophagic pathway. However, comprehensive characterization of autophagy genes and their clinical relevance in cancer is still lacking. Here, we systematically characterized alterations of autophagy genes in multiple cancer lines by analyzing data from The Cancer Genome Atlas and CellMiner database. Interactions between autophagy genes and clinically actionable genes (CAGs) were identified by analyzing co-expression, protein-protein interactions (PPIs) and transcription factor (TF) data. A key subnetwork was identified that included 18 autophagy genes and 22 CAGs linked by 28 PPI pairs and 1 TF-target pair, which was EGFR targeted by RARA. Alterations in the expression of autophagy genes were associated with patient survival in multiple cancer types. RARA and EGFR were associated with worse survival in colorectal cancer patients. The regulatory role of EGFR in 5-FU resistance was validated in colon cancer cells in vivo and in vitro. EGFR contributed to 5-FU resistance in colon cancer cells through autophagy induction, and EGFR overexpression in 5-FU resistant colon cancer was regulated by RARA. The present study provides a comprehensive analysis of autophagy in different cancer cell lines and highlights the potential clinical utility of targeting autophagy genes.

2.
J Nanosci Nanotechnol ; 20(5): 3105-3116, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31635654

RESUMO

The Z-scheme Bi2WO6/NaBiO3 nanocomposites were first fabricated by a facile hydrothermal method, and were then characterized by X-ray diffraction, transmission electron microscopy, scanning electron microscopy, energy dispersive spectrometer, Fourier-transform-infrared spectroscopy, X-ray photoelectron spectroscopy and N2 adsorption-desorption. The as-prepared Bi2WO6/NaBiO3 nanocomposites exhibit outstanding photocatalytic activity and recyclability. A 98.4% photodegradation of 2,3-dichlorophenol (50 mg·L-1) was attained in the presence of Bi2WO6/NaBiO3 (1:10) under the visible-light irradiation in 30 min. In particular, the photocatalytic mechanism has been discussed in detail, based on four aspects: (1) oxidative species, (2) photoelectrochemical performance, (3) conduction band and valence band energy levels and (4) possible transition states and reactions. In conclusion, O-2 is the main active oxidative species in the Bi2WO6/NaBiO3 nanocomposite. The material has higher photocurrent and visible light adsorption but lower electron-hole pairs recombination, which contributes to distinguished photocatalytic efficiency. The Z-scheme photocatalytic path was proposed and the possible degradation process and routes have been summarized.

3.
Phytochemistry ; 147: 125-131, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29306798

RESUMO

The investigation of the fruits of Solanum nigrum led to the isolation of four previously undescribed steroidal alkaloids, named solanine A, 7α-OH khasianine, 7α-OH solamargine and 7α-OH solasonine, together with six known ones. The structures of the isolated compounds were elucidated unambiguously by spectroscopic data analyses and chemical methods. Solanine A represents an unusual steroidal alkaloid with an unprecedented 6/5/6/5/5/6 hexacyclic ring system, and its structure was confirmed by X-ray single crystal diffraction analysis. Compounds 2-4 were rare naturally occurring steroidal alkaloid glycosides bearing a hydroxyl group at C-7 position. Solanine A showed the most potent inhibitory activity against the LPS-induced NO production in murine RAW264.7 macrophages with an IC50 value of 3.85 ± 0.71 µM and significant cytotoxicity against MGC803, HepG2 and SW480 cancer cell lines with IC50 values of 6.00 ± 0.52 µM, 9.25 ± 0.49 µM and 6.23 ± 0.26 µM, respectively.


Assuntos
Alcaloides/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Medicamentos de Ervas Chinesas/química , Frutas/química , Solanum nigrum/química , Esteroides/farmacologia , Alcaloides/química , Alcaloides/isolamento & purificação , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Medicina Tradicional Chinesa , Camundongos , Estrutura Molecular , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Células RAW 264.7 , Esteroides/química , Esteroides/isolamento & purificação , Relação Estrutura-Atividade
4.
Fitoterapia ; 118: 6-12, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28214554

RESUMO

Four new C21 steroidal glycosides (1-4), named perisepiumosides FI (1-4) together with six known steroidal glycosides (5-10) and four oligosaccharides (11-14), were isolated from the root bark of Periploca sepium. Their structures were characterized on the basis of 1D and 2D-NMR spectroscopic data as well as HR-ESI-MS analysis. The evaluation of inhibition activity against human A-549 and HepG2 cell lines indicated that compounds 2, 8, 10 and 13 showed different levels of cytotoxic activities with IC50 values ranging from 0.61 to 7.86µM.


Assuntos
Glicosídeos/química , Oligossacarídeos/química , Periploca/química , Raízes de Plantas/química , Células A549 , Glicosídeos/isolamento & purificação , Células Hep G2 , Humanos , Estrutura Molecular , Oligossacarídeos/isolamento & purificação
5.
Mol Cancer ; 16(1): 9, 2017 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-28086904

RESUMO

BACKGROUND: With more than 600,000 mortalities each year, colorectal cancer (CRC) is the third most commonly diagnosed type of cancer worldwide. Recently, mechanisms involving noncoding RNAs have been implicated in the development of CRC. METHODS: We examined expression levels of lncRNA CRNDE and miR-181a-5p in 64 cases of CRC tissues and cell lines by qRT-PCR. Gain-of-function and loss-of-function assays were performed to examine the effect of CRNDE and miR-181a-5p on proliferation and chemoresistance of CRC cells. Using fluorescence reporter and western blot assays, we also explored the possible mechanisms of CRNDE in CRC cells. RESULTS: In this study, we found that the expression levels of the CRNDE were upregulated in CRC clinical tissue samples. We identified microRNA miR-181a-5p as an inhibitory target of CRNDE. Both CRNDE knockdown and miR-181a-5p overexpression in CRC cell lines led to inhibited cell proliferation and reduced chemoresistance. We also determined that ß-catenin and TCF4 were inhibitory targets of miR-181a-5p, and that Wnt/ß-catenin signaling was inhibited by both CRNDE knockdown and miR-181a-5p overexpression. Significantly, we found that the repression of cell proliferation, the reduction of chemoresistance, and the inhibition of Wnt/ß-catenin signaling induced by CRNDE knockdown would require the increased expression of miR-181a-5p. CONCLUSIONS: Our study demonstrated that the lncRNA CRNDE could regulate the progression and chemoresistance of CRC via modulating the expression levels of miR-181a-5p and the activity of Wnt/ß-catenin signaling.


Assuntos
Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , RNA Longo não Codificante/genética , Via de Sinalização Wnt , Adulto , Idoso , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Interferência de RNA , Fator de Transcrição 4 , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Carga Tumoral , beta Catenina/genética , beta Catenina/metabolismo
6.
Oncotarget ; 7(21): 31111-21, 2016 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-27145271

RESUMO

The erythropoietin-producing hepatocyte (Eph) family tyrosine kinases play important roles in tumorigenesis and cancer aggression. In this study, we investigated the role of EphB6 in oncogenic transformation of colorectal epithelial cells in vitro and in vivo. EphB6 is upregulated in human colorectal cancer (CRC) tissues as compared to normal tissues, and its overexpression promotes proliferation, migration and invasion by IMCE colorectal adenoma cells, in which one Apc allele is mutated. EphB6 overexpression together with Apc mutation leads to the development of colorectal tumors in vivo. Expression microarrays using mRNAs and lncRNAs isolated from EphB6-overexpresssing IMCE and control cells revealed a large number of dysregulated genes involved in cancer-related functions and pathways. The present study is the first to demonstrate that EphB6 overexpression together with Apc gene mutations may enhance proliferation, invasion and metastasis by colorectal epithelial cells. Microarray data and pathway analysis of differentially expressed genes provided insight into possible EphB6-regulated mechanisms promoting tumorigenesis and cancer progression. EphB6 overexpression may represent a novel, effective biomarker predictive of cell proliferation, invasion and metastasis patterns in CRC tumors.


Assuntos
Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Genes APC , Mutação , Receptores da Família Eph/biossíntese , Animais , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Colorretais/patologia , Regulação Neoplásica da Expressão Gênica , Xenoenxertos , Humanos , Camundongos , Camundongos Nus , Ratos , Receptores da Família Eph/genética , Transdução de Sinais , Transfecção
7.
Ultrastruct Pathol ; 36(6): 381-6, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23216236

RESUMO

The aim was to investigate the expression of the CXCR4 protein in five molecular subtypes of breast cancer. The authors randomly selected the breast cancer paraffin-embedded specimens of the Affiliated Third Hospital of Harbin Medical University between 2007 and 2009. Details are as follows: basal-like subtype-ER (-), PR (-), C-erbB-2 (-), CK5/6 (+), n = 36; normal breast subtype-ER (-), PR (-), C-erbB-2 (-), CK5/6(-), n = 40; luminal A subtype-ER/PR (+), C-erbB-2 (-), n = 38; luminal B subtype-ER/PR (+), C-erbB-2 (+), n = 60; C-erbB-2 (+) subtype-ER (-), PR (-), C-erbB-2 (+), n = 58. Using the immunohistochemistry method, the authors detected the expression of the CXCR4 protein in the five subtypes. The CXCR4 protein expression in the basal-like subtype was the highest, and that in the luminal A subtype was the lowest. In terms of five molecular subtypes of breast cancer, the differences in CXCR4 protein expression were significant (p < .001). In terms of C-erbB-2 expression, tumor stage, and lymph node metastasis of breast cancer, the differences in CXCR4 protein expression were significant (p < .01).


Assuntos
Biomarcadores Tumorais/análise , Neoplasias da Mama/química , Receptores CXCR4/análise , Neoplasias da Mama/classificação , Neoplasias da Mama/patologia , Distribuição de Qui-Quadrado , Feminino , Humanos , Imuno-Histoquímica , Queratina-5/análise , Queratina-6/análise , Metástase Linfática , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Receptor ErbB-2/análise , Receptores Estrogênicos/análise , Receptores de Progesterona/análise
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