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1.
Zhonghua Kou Qiang Yi Xue Za Zhi ; 56(6): 549-556, 2021 Jun 09.
Artigo em Chinês | MEDLINE | ID: mdl-34098670

RESUMO

Objective: To investigate the effects of Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) of type Ⅰand Ⅳ fimA on the proliferation and migration of human umbilical artery smooth muscle cells (HUASMC) under co-culture conditions and to explore the biological basis and possible mechanisms of the relationship between periodontitis and atherosclerosis (As). Methods: Type Ⅰ and Ⅳ fimA Pg were anaerobically cultured and the Pg-LPS was extracted, purified and identified. Human umbilical vein endothelial cells (HUVEC) and HUASMC were cultured in vitro and the HUVEC-HUASMC co-cultured cell model was established using rat tail type Ⅰ collagen. The experiment was divided into three groups: group T1 (co-cultured cells were stimulated with type Ⅰ fimA Pg-LPS at the mass concentrations of 0.5, 1.0, 2.0, 5.0, 10.0 mg/L), group T2 (co-cultured cells were stimulated with type Ⅳ fimA Pg-LPS at the mass concentrations of 0.5, 1.0, 2.0, 5.0, 10.0 mg/L), and negative control group (without LPS). Cell counting kit-8 (CCK-8) was used to detect the proliferation ability of HUASMC and the migration ability of HUASMC was observed by using the Transwell migration chamber. Comparasons of the changes in the proliferation and migration ability of HUASMC after 2, 8, 24 and 48 h of Pg-LPS stimulated co-cultured cells with various mass concentrations of Pg-LPS were conducted. Results: For the co-cultured cells under the action of type Ⅰ and Ⅳ fimA Pg-LPS, at 24 and 48 h, in each mass concentration group of the two types of Pg-LPS (0.5, 1.0, 2.0, 5.0, 10.0 mg/L), HUASMC's A values were significantly up-regulated compared to the negative control group (P<0.05) and for the co-cultured cells after the stimulation of type Ⅳ fimA Pg-LPS at concentrations of 5 and 10 mg/L at 48 h, the A values (1.386±0.044, 1.455±0.058) of HUASMC were significantly higher than that of HUASMC (1.168±0.064, 1.204±0.088) in the same concentrations of type Ⅰ fimA Pg-LPS (P<0.05). In addition, the A values of HUASMC in stimulated co-cultured cells under concentrations of 5.0 and 10.0 mg/L of type Ⅳ fimA Pg-LPS at 48 h were significantly higher than that in stimulated co-culture cells under the concentrations of 0.5 and 1.0 mg/L of type Ⅳ fimA Pg-LPS (1.170±0.082, 1.239±0.089) (P<0.05). The migration results of HUASMC showed that at 8, 24, and 48 h, the numbers of migration of HUASMC in each mass concentration group of type Ⅰ and Ⅳ fimA Pgas-LPS were significantly higher than that of HUASMC under the same Pg-LPS mass concentration at 2 h in the same group (P<0.05). The migration quantities of HUASMC in the other Pg-LPS mass concentration groups at 48 h were significantly higher than that of HUASMC under the same Pg-LPS mass concentration at 24 h in the same group (P<0.05), except for 10.0 mg/L type Ⅳ fimA Pg-LPS. The numbers of HUASMC migration in 2.0 mg/L type Ⅳ fimA Pg-LPS stimulated co-cultured cells at 48 h (204.00±20.98) were significantly higher than that in type Ⅰ fimA Pg-LPS stimulated co-culture cells at the same concentration (141.89±18.28) (P<0.05). Further more, at the same observation time point, the higher the Pg-LPS concentration, the greater the number of HUASMC migration (P<0.05). Conclusions: Both Ⅰ and Ⅳ fimA Pg-LPS could enhance the proliferation and migration ability of HUASMC in the co-culture system, and the virulence of Pg-LPS might be related to the fimA genotype. Ⅳ fimA Pg-LPS showed a more significant stimulating effect and more likely to cause HUASMC dysfunction than Ⅰ fimA Pg-LPS, which provided part of the basis for the progression of As in severe periodontitis.


Assuntos
Lipopolissacarídeos , Porphyromonas gingivalis , Animais , Proliferação de Células , Técnicas de Cocultura , Humanos , Miócitos de Músculo Liso , Ratos , Artérias Umbilicais
2.
Zhonghua Kou Qiang Yi Xue Za Zhi ; 56(6): 604-607, 2021 Jun 09.
Artigo em Chinês | MEDLINE | ID: mdl-34098679

RESUMO

Dental pulp stem cell (DPSC), with a high capacity of multidirectional differentiation, is the key and preferred cell in the study of dental pulp and dentin regeneration. The effect of trace elements on the differentiation of DPSC is one of the research hotspots in the field of oral tissue engineering in recent years. Trace elements have a wide range of physiological and biochemical functions. It can directly regulate the differentiation, migration and proliferation capacity of DPSC, while can indirectly affect the differentiation of DPSC by exerting antibacterial and immune function regulation or changing the physical and chemical properties of the scaffold material. To clarify the role of trace elements in the differentiation of DPSC can provide more reference for the realization of pulp and dentin regeneration. This paper will review the recent research progress on the effects of relevant trace elements on the differentiation of DPSC into odontogenesis and angiogenesis.


Assuntos
Polpa Dentária , Oligoelementos , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Odontogênese , Células-Tronco
3.
Gen Physiol Biophys ; 40(3): 207-219, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34100377

RESUMO

Circular RNAs (circRNAs) are related to rheumatoid arthritis (RA) development. However, the function and mechanism of circRNA pituitary tumor-transforming 1 interacting protein (circ- PTTG1IP) in RA are unknown. The expression of circ-PTTG1IP in synovial tissues of RA patients and fibroblast-like synoviocytes from RA patients (RA-FLSs) were detected by RT-qPCR. The results uncovered that circ-PTTG1IP was overexpressed in RA patients and RA-FLSs, and circ-PTTG1IP knockdown suppressed cell proliferation, migration, invasion and inflammatory response in RA-FLSs. Besides, we found that circ-PTTG1IP could directly bind to miR-671-5p, and toll-like receptor 4 (TLR4) was a target of miR-671-5p, which was confirmed by dual-luciferase reporter assay. miR-671-5p inhibitor attenuated the effects of circ-PTTG1IP knockdown on RA-FLSs, while the effects of miR-671-5p mimic on RA-FLSs were partly reversed by TLR4 overexpression. Furthermore, circ-PTTG1IP could upregulate TLR4 expression by miR-671-5p. Thus, circ-PTTG1IP knockdown repressed cell proliferation, migration, invasion and inflammatory response in RA-FLSs by regulating the miR-671-5p/TLR4 axis.


Assuntos
Artrite Reumatoide , MicroRNAs , Sinoviócitos , Apoptose , Artrite Reumatoide/genética , Proliferação de Células , Células Cultivadas , Fibroblastos , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , MicroRNAs/genética , Receptor 4 Toll-Like/genética
4.
Gen Physiol Biophys ; 40(3): 245-252, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34100380

RESUMO

Although the medical science has been developed for decades, the molecular mechanism of endometrial cancer (EC) is not yet completely clear. Previous studies have shown that the tripartite motif containing 28 (TRIM28) plays a crucial role in tumor development. However, TRIM28 is rarely studied in EC, and its role and mechanism need to be further determined. This study was aimed to delve into the related molecular mechanism underling the role of TRIM28 in EC cell growth and migration. qPCR assays and Western blot assays revealed that the expression level of TRIM28 was higher in EC tissues or cell lines (HEC1B, AN3CA, and Ishikawa) than normal tissue or human endometrial epithelial cells (hEEC), respectively. Then, CCK-8 cell viability assay and clone formation assay were performed in HEC1B and AN3CA cell lines after overexpression or knockdown of TRIM28. The results verified that suppression of TRIM28 expression inhibited the proliferation of EC cells. The wound scratch healing assay and transwell assay were performed in HEC1B and AN3CA cell lines after overexpression or knockdown of TRIM28. The results showed that suppression of TRIM28 expression inhibited the invasion and migration of EC cells. Finally, the Western blot assays hinted that overexpression or knockdown of TRIM28 in HEC1B and AN3CA cell lines would promote or inhibit the phosphorylation of AKT and mTOR protein. These findings indicated that TRIM28 promoted the growth and migration of EC cells via regulating the AKT/mTOR pathway.


Assuntos
Neoplasias do Endométrio , Proteínas Proto-Oncogênicas c-akt , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Neoplasias do Endométrio/genética , Feminino , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Proteína 28 com Motivo Tripartido
5.
Nat Commun ; 12(1): 3444, 2021 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-34103528

RESUMO

AKT is involved in a number of key cellular processes including cell proliferation, apoptosis and metabolism. Hyperactivation of AKT is associated with many pathological conditions, particularly cancers. Emerging evidence indicates that arginine methylation is involved in modulating AKT signaling pathway. However, whether and how arginine methylation directly regulates AKT kinase activity remain unknown. Here we report that protein arginine methyltransferase 5 (PRMT5), but not other PRMTs, promotes AKT activation by catalyzing symmetric dimethylation of AKT1 at arginine 391 (R391). Mechanistically, AKT1-R391 methylation cooperates with phosphatidylinositol 3,4,5 trisphosphate (PIP3) to relieve the pleckstrin homology (PH)-in conformation, leading to AKT1 membrane translocation and subsequent activation by phosphoinositide-dependent kinase-1 (PDK1) and the mechanistic target of rapamycin complex 2 (mTORC2). As a result, deficiency in AKT1-R391 methylation significantly suppresses AKT1 kinase activity and tumorigenesis. Lastly, we show that PRMT5 inhibitor synergizes with AKT inhibitor or chemotherapeutic drugs to enhance cell death. Altogether, our study suggests that R391 methylation is an important step for AKT activation and its oncogenic function.


Assuntos
Arginina/metabolismo , Carcinogênese/metabolismo , Carcinogênese/patologia , Proteína-Arginina N-Metiltransferases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Antineoplásicos/farmacologia , Biocatálise/efeitos dos fármacos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Proliferação de Células/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Feminino , Células HEK293 , Humanos , Metilação/efeitos dos fármacos , Camundongos Nus , Mutação/genética , Ligação Proteica/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Proteína-Arginina N-Metiltransferases/deficiência , Proteínas Proto-Oncogênicas c-akt/química , Piruvato Desidrogenase Quinase de Transferência de Acetil/metabolismo , RNA Interferente Pequeno/metabolismo , Transdução de Sinais/efeitos dos fármacos
6.
Hematol Oncol ; 39 Suppl 1: 83-87, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34105816

RESUMO

Follicular lymphoma (FL) is a paradigm of tumors that require the interaction between tumor and microenvironment cells to foster their development from initial steps to progression. Recent large-scale genome studies have uncovered multiple genetic alterations of FL that influence the microenvironment in two main directions, promoting tumor cell survival and proliferation and facilitating their evasion from immune antitumor signals. Understanding the crosstalk between tumor B-cells and the microenvironment will facilitate the identification of vulnerabilities that may offer novel targets for treatment of the patients. This review highlights recent findings showing the effect of common genetic mutations modulating the cell composition of the tumor microenvironment and the novel therapeutic perspectives to target these interactions.


Assuntos
Linfócitos B , Proliferação de Células , Linfoma Folicular , Mutação , Microambiente Tumoral , Linfócitos B/imunologia , Linfócitos B/patologia , Sobrevivência Celular/genética , Sobrevivência Celular/imunologia , Humanos , Linfoma Folicular/genética , Linfoma Folicular/imunologia , Linfoma Folicular/patologia , Linfoma Folicular/terapia , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia
7.
Int J Mol Sci ; 22(11)2021 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-34072471

RESUMO

Organochlorine pesticides constitute the majority of the total environmental pollutants, and a wide range of compounds have been found to be carcinogenic to humans. Among all, growing interest has been focused on ß-hexachlorocyclohexane (ß-HCH), virtually the most hazardous and, at the same time, the most poorly investigated member of the hexachlorocyclohexane family. Considering the multifaceted biochemical activities of ß-HCH, already established in our previous studies, the aim of this work is to assess whether ß-HCH could also trigger cellular malignant transformation toward cancer development. For this purpose, experiments were performed on the human normal bronchial epithelium cell line BEAS-2B exposed to 10 µM ß-HCH. The obtained results strongly support the carcinogenic potential of ß-HCH, which is achieved through both non-genotoxic (activation of oncogenic signaling pathways and proliferative activity) and indirect genotoxic (ROS production and DNA damage) mechanisms that significantly affect cellular macroscopic characteristics and functions such as cell morphology, cell cycle profile, and apoptosis. Taking all these elements into account, the presented study provides important elements to further characterize ß-HCH, which appears to be a full-fledged carcinogenic agent.


Assuntos
Carcinógenos/farmacologia , Transformação Celular Neoplásica/induzido quimicamente , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Hexaclorocicloexano/farmacologia , Mucosa Respiratória/efeitos dos fármacos , Mucosa Respiratória/patologia , Apoptose/efeitos dos fármacos , Biomarcadores , Biomarcadores Tumorais , Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células , Células Cultivadas , Células Epiteliais/metabolismo , Expressão Gênica , Hexaclorocicloexano/efeitos adversos , Humanos , Espécies Reativas de Oxigênio/metabolismo , Mucosa Respiratória/metabolismo , Transdução de Sinais/efeitos dos fármacos
8.
Braz J Med Biol Res ; 54(9): e10390, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34076140

RESUMO

Sorafenib (SOR) resistance is still a significant challenge for the effective treatment of hepatocellular carcinoma (HCC). The mechanism of sorafenib resistance remains unclear. Several microRNAs (miRNAs) have been identified as playing a role in impairing the sensitivity of tumor cells to treatment. We examined the mechanism behind the role of miR-92b in mediating sorafenib resistance in HCC cells. We detected that miR-92b expression was significantly upregulated in SOR-resistant HepG2/SOR cells compared to parental HepG2/WT cells. After transfection with miR-92b inhibitor, the proliferation of HepG2/SOR cells was remarkably weakened and rates of apoptosis significantly increased. PTEN was considered to be a functional target of miR-92b according to a luciferase reporter assay. Knockdown of PTEN significantly impaired the ability of miR-92b inhibitor on increasing sorafenib sensitivity of HepG2/SOR cells. Furthermore, we confirmed by western blotting and immunofluorescence that miR-92b can mediate sorafenib resistance by activating the PI3K/AKT/mTOR pathway in HCC cells by directly targeting PTEN. These findings further validate the mechanism of miR-92b in SOR resistance in HCC treatment.


Assuntos
Carcinoma Hepatocelular , Resistencia a Medicamentos Antineoplásicos , Neoplasias Hepáticas , MicroRNAs , Sorafenibe , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , MicroRNAs/genética , PTEN Fosfo-Hidrolase/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Sorafenibe/farmacologia , Serina-Treonina Quinases TOR
9.
Cells ; 10(5)2021 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-34066434

RESUMO

Viral pathogens often exploit host cell regulatory and signaling pathways to ensure an optimal environment for growth and survival. Several studies have suggested that 5'-adenosine monophosphate-activated protein kinase (AMPK), an intracellular serine/threonine kinase, plays a significant role in the modulation of infection. Traditionally, AMPK is a key energy regulator of cell growth and proliferation, host autophagy, stress responses, metabolic reprogramming, mitochondrial homeostasis, fatty acid ß-oxidation and host immune function. In this review, we highlight the modulation of host AMPK by various viruses under physiological conditions. These intracellular pathogens trigger metabolic changes altering AMPK signaling activity that then facilitates or inhibits viral replication. Considering the COVID-19 pandemic, understanding the regulation of AMPK signaling following infection can shed light on the development of more effective therapeutic strategies against viral infectious diseases.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Antivirais/farmacologia , Transdução de Sinais/imunologia , Viroses/imunologia , Antivirais/uso terapêutico , Autofagia/efeitos dos fármacos , Autofagia/imunologia , COVID-19/tratamento farmacológico , COVID-19/epidemiologia , COVID-19/imunologia , Proliferação de Células/efeitos dos fármacos , Desenvolvimento de Medicamentos , Humanos , Pandemias/prevenção & controle , SARS-CoV-2/imunologia , Transdução de Sinais/efeitos dos fármacos , Viroses/tratamento farmacológico , Replicação Viral/efeitos dos fármacos , Replicação Viral/imunologia
10.
Int J Mol Sci ; 22(10)2021 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-34068421

RESUMO

Resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) is a major obstacle in managing lung cancer. The root of Scutellaria baicalensis (SB) traditionally used for fever clearance and detoxification possesses various bioactivities including anticancer effects. The purpose of this study was to investigate whether SB exhibited anticancer activity in EGFR TKI-resistant lung cancer cells and to explore the underlying mechanism. We used four types of human lung cancer cell lines, including H1299 (EGFR wildtype; EGFR TKI-resistant), H1975 (acquired TKI-resistant), PC9/ER (acquired erlotinib-resistant), and PC9/GR (acquired gefitinib-resistant) cells. The ethanol extract of SB (ESB) decreased cell viability and suppressed colony formation in the four cell lines. ESB stimulated nuclear fragmentation and the cleavage of poly(ADP-ribose) polymerase (PARP) and caspase-3. Consistently, the proportion of sub-G1 phase cells and annexin V+ cells were significantly elevated by ESB, indicating that ESB induced apoptotic cell death in EGFR TKI-resistant cells. ESB dephosphorylated signal transducer and activator of transcription 3 (STAT3) and downregulated the target gene expression. The overexpression of constitutively active STAT3 reversed ESB-induced apoptosis, suggesting that ESB triggered apoptosis in EGFR TKI-resistant cells by inactivating STAT3. Taken together, we propose the potential use of SB as a novel therapeutic for lung cancer patients with EGFR TKI resistance.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Neoplasias Pulmonares/patologia , Extratos Vegetais/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Fator de Transcrição STAT3/antagonistas & inibidores , Scutellaria baicalensis/química , Apoptose , Proliferação de Células , Receptores ErbB/antagonistas & inibidores , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Raízes de Plantas/química , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Células Tumorais Cultivadas
11.
Int J Mol Sci ; 22(10)2021 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-34068438

RESUMO

Histone deacetylase inhibitors (HDIs) are promising anti-cancer agents that inhibit proliferation of many types of cancer cells including breast carcinoma (BC) cells. In the present study, we investigated the influence of the Notch1 activity level on the pharmacological interaction between cisplatin (CDDP) and two HDIs, valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA, vorinostat), in luminal-like BC cells. The type of drug-drug interaction between CDDP and HDIs was determined by isobolographic analysis. MCF7 cells were genetically modified to express differential levels of Notch1 activity. The cytotoxic effect of SAHA or VPA was higher on cells with decreased Notch1 activity and lower for cells with increased Notch1 activity than native BC cells. The isobolographic analysis demonstrated that combinations of CDDP with SAHA or VPA at a fixed ratio of 1:1 exerted additive or additive with tendency toward synergism interactions. Therefore, treatment of CDDP with HDIs could be used to optimize a combined therapy based on CDDP against Notch1-altered luminal BC. In conclusion, the combined therapy of HDIs and CDDP may be a promising therapeutic tool in the treatment of luminal-type BC with altered Notch1 activity.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Cisplatino/farmacologia , Interações Medicamentosas , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Inibidores de Histona Desacetilases/farmacologia , Receptor Notch1/metabolismo , Antineoplásicos/farmacologia , Apoptose , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Proliferação de Células , Sinergismo Farmacológico , Quimioterapia Combinada , Feminino , Humanos , Células MCF-7 , Receptor Notch1/genética
12.
Int J Mol Sci ; 22(10)2021 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-34068442

RESUMO

Advanced glycation end products (AGEs) are produced in response to a high-glucose environment and oxidative stress and exacerbate various diseases. Nε-(Carboxymethyl)lysine (CML) is an AGE that is produced by the glycation of lysine residues of proteins. There are a few reports on alterations in protein function due to CML modification; however, its association with cancer is not clear. We investigated the significance of CML modification in high mobility group box protein-1 (HMGB1), a cytokine that is significantly associated with cancer progression. Treatment of the gastric cancer cell lines TMK1 and MKN74 with glyoxal or glucose resulted in increased CML modification compared to untreated cells. CML-HMGB1 was modified via oxidation and more pronouncedly activated the receptor for AGE and downstream AKT and NF-κB compared to naïve HMGB1 and oxidized HMGB1. CML-HMGB1 bound with reduced affinity to DNA and histone H3, resulting in enhanced extranuclear translocation and extracellular secretion. Treatment of gastric cancer cells with CML-HMGB1 enhanced cell proliferation and invasion, sphere formation, and protection from thapsigargin-induced apoptosis, and decreased 5-FU sensitivity in comparison to HMGB1. Further, CML-HMGB1 was detected at various levels in all the 10 gastric cancer tumor specimens. HMGB1 levels correlated with primary tumor progression and distant metastasis, whereas CML-HMGB1 levels were associated with primary tumor progression, lymph node metastasis, distant metastasis, and stage. In addition, CML-HMGB1 levels correlated with oxidative stress in cancer tissues and resistance to neoadjuvant therapy. Therefore, CML modification of HMGB1 enhanced the cancer-promoting effect of HMGB1. In this study, CML-HMGB1 has been highlighted as a new therapeutic target, and analysis of the molecular structure of CML-HMGB1 is desired in the future.


Assuntos
Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , Produtos Finais de Glicação Avançada/metabolismo , Proteína HMGB1/metabolismo , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Neoplasias Gástricas/patologia , Apoptose , Biomarcadores Tumorais/genética , Movimento Celular , Proliferação de Células , Glicosilação , Proteína HMGB1/genética , Humanos , Prognóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Células Tumorais Cultivadas
13.
Int J Mol Sci ; 22(10)2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-34068980

RESUMO

Ultraviolet (UV) exposure has been linked to skin damage and carcinogenesis, but recently UVB has been proposed as a therapeutic approach for cancer. Herein, we investigated the cellular and molecular effects of UVB in immortal and tumorigenic HPV positive and negative cells. Cells were irradiated with 220.5 to 1102.5 J/m2 of UVB and cell proliferation was evaluated by crystal violet, while cell cycle arrest and apoptosis analysis were performed through flow cytometry. UVB effect on cells was recorded at 661.5 J/m2 and it was exacerbated at 1102.5 J/m2. All cell lines were affected by proliferation inhibition, cell cycle ablation and apoptosis induction, with different degrees depending on tumorigenesis level or HPV type. Analysis of the well-known UV-responsive p53, E2F1 and microtubules system proteins was performed in SiHa cells in response to UVB through Western-blotting assays. E2F1 and the Microtubule-associated protein 2 (MAP2) expression decrease correlated with cellular processes alteration while p53 and Microtubule-associated Protein 1S (MAP1S) expression switch was observed since 882 J/m2, suggesting they were required under more severe cellular damage. However, expression transition of α-Tubulin3C and ß-Tubulin was abruptly noticed until 1102.5 J/m2 and particularly, γ-Tubulin protein expression remained without alteration. This study provides insights into the effect of UVB in cervical cancer cell lines.


Assuntos
Fator de Transcrição E2F1/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Microtúbulos/efeitos da radiação , Proteína Supressora de Tumor p53/metabolismo , Raios Ultravioleta , Neoplasias do Colo do Útero/patologia , Apoptose , Ciclo Celular , Proliferação de Células , Fator de Transcrição E2F1/genética , Feminino , Humanos , Células Tumorais Cultivadas , Proteína Supressora de Tumor p53/genética , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/radioterapia
14.
Int J Mol Sci ; 22(10)2021 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-34069970

RESUMO

Prostate cancer (PCa) is the second most leading cause of death in males. Our previous studies have demonstrated that δ-catenin plays an important role in prostate cancer progression. However, the molecular mechanism underlying the regulation of δ-catenin has not been fully explored yet. In the present study, we found that δ-catenin could induce phosphorylation of p21Waf and stabilize p21 in the cytoplasm, thus blocking its nuclear accumulation for the first time. We also found that δ-catenin could regulate the interaction between AKT and p21, leading to phosphorylation of p21 at Thr-145 residue. Finally, EGF was found to be a key factor upstream of AKT/δ-catenin/p21 for promoting proliferation and metastasis in prostate cancer. Our findings provide new insights into molecular controls of EGF and the development of potential therapeutics targeting δ-catenin to control prostate cancer progression.


Assuntos
Cateninas/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Fator de Crescimento Epidérmico/metabolismo , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transporte Ativo do Núcleo Celular , Sítios de Ligação/genética , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Inibidor de Quinase Dependente de Ciclina p21/química , Inibidor de Quinase Dependente de Ciclina p21/genética , Humanos , Ligantes , Masculino , Modelos Biológicos , Mutagênese Sítio-Dirigida , Invasividade Neoplásica/patologia , Invasividade Neoplásica/fisiopatologia , Células PC-3 , Fosforilação , Neoplasias da Próstata/genética , Domínios e Motivos de Interação entre Proteínas , Estabilidade Proteica , Proteínas Proto-Oncogênicas c-akt/química , Transdução de Sinais , Treonina/química
15.
Int J Mol Sci ; 22(10)2021 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-34070163

RESUMO

Preeclampsia is associated with an increased cardiovascular morbidity of mother and offspring, thus contributing to a substantial burden in women and children's health. It has been proven that endothelial progenitor cell (EPC) numbers and functional characteristics are impaired in cardiovascular disease and preeclampsia, although causative factors for the latter have remained elusive. MicroRNA (miRNA) modifications are a potential mechanism through which exposure to an altered environment translates into the development of chronic disease. In this study, we examined whether development of preeclampsia corresponds to alterations of miRNAs in maternal- and cord-blood-derived EPC. To test this end, we analyzed maternal and neonatal miRNAs via RNA sequencing from endothelial cells of preeclamptic and healthy controls in different cell culture passages. We were able to demonstrate differentially represented miRNAs in all groups. Hsa-miR-1270 showed significantly different levels in cord blood EPC from preeclampsia versus control and was negatively correlated with mRNA levels of its predicted targets ANGPTL7 and TFRC. Transfection with an hsa-miR-1270 inhibitor decreased the tube formation capacity and chemotactic motility but did not change proliferation in vitro. Target predictions and gene set enrichment analyses identified alternative splicing as a significantly enriched pathway for hsa-miR-1270. The top miRNAs in three other groups were predicted to target transcriptional and developmental pathways. Here, we showed for the first time significantly different levels of miRNAs and differently represented mRNA levels of predicted target genes in EPC derived from preeclampsia. Understanding the effects of preeclampsia on the epigenetic mechanisms of EPC will be crucial and may provide initial insights for further evaluation of the benefits of therapies targeting this cell population.


Assuntos
Células Progenitoras Endoteliais/metabolismo , MicroRNAs/genética , Pré-Eclâmpsia/genética , Adulto , Proteínas Semelhantes a Angiopoietina/genética , Antígenos CD/genética , Estudos de Casos e Controles , Proliferação de Células , Células Cultivadas , Quimiotaxia , Feminino , Sangue Fetal/citologia , Sangue Fetal/metabolismo , Perfilação da Expressão Gênica , Humanos , Recém-Nascido , Masculino , MicroRNAs/sangue , MicroRNAs/metabolismo , Neovascularização Patológica/genética , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/metabolismo , Gravidez , RNA Mensageiro/sangue , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores da Transferrina/genética , Adulto Jovem
16.
Int J Mol Sci ; 22(10)2021 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-34070207

RESUMO

In domestic ruminants, endometrial receptivity is related to successful pregnancy and economic efficiency. Despite several molecules having been reported in the past regarding endometrial receptivity regulation, much regarding the mechanism of endometrial receptivity regulation remains unknown due to the complex nature of the trait. In this work, we demonstrated that the cysteine-rich transmembrane bone morphogenetic protein (BMP) regulator 1 (CRIM1) served as a novel regulator in the regulation of goat endometrial receptivity in vitro. Our results showed that hormones and IFN-τ increased the expression of CRIM1 in goat endometrial epithelial cells (EECs). Knockdown of CRIM1 via specific shRNA hindered cell proliferation, cell adhesion and prostaglandins (PGs) secretion and thus derailed normal endometrial receptivity. We further confirmed that receptivity defect phenotypes due to CRIM1 interference were restored by ATG7 overexpression in EECs while a loss of ATG7 further impaired receptivity phenotypes. Moreover, our results showed that changing the expression of ATG7 affected the reactive oxygen species (ROS) production. Moreover, mR-143-5p was shown to be a potential upstream factor of CRIM1-regulated endometrial receptivity in EECs. Overall, these results suggest that CRIM1, as the downstream target of miR-143-5p, has effects on ATG7-dependent autophagy, regulating cell proliferation, cell adhesion and PG secretion, and provides a new target for the diagnosis and treatment of early pregnancy failure and for improving the success rates of artificial reproduction.


Assuntos
Receptores de Proteínas Morfogenéticas Ósseas/fisiologia , Implantação do Embrião/genética , Endométrio/fisiologia , Cabras/fisiologia , Animais , Autofagia/efeitos dos fármacos , Autofagia/genética , Autofagia/fisiologia , Proteína 7 Relacionada à Autofagia/deficiência , Proteína 7 Relacionada à Autofagia/genética , Proteína 7 Relacionada à Autofagia/fisiologia , Receptores de Proteínas Morfogenéticas Ósseas/antagonistas & inibidores , Receptores de Proteínas Morfogenéticas Ósseas/genética , Adesão Celular , Proliferação de Células , Células Cultivadas , Implantação do Embrião/fisiologia , Endométrio/citologia , Endométrio/efeitos dos fármacos , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/fisiologia , Estradiol/farmacologia , Feminino , Técnicas de Silenciamento de Genes , Cabras/genética , Interferon Tipo I/farmacologia , MicroRNAs/genética , MicroRNAs/metabolismo , Modelos Biológicos , Gravidez , Proteínas da Gravidez/farmacologia , Progesterona/farmacologia , Prostaglandinas/metabolismo , RNA Interferente Pequeno/genética , Espécies Reativas de Oxigênio/metabolismo , Regulação para Cima
17.
Nat Prod Res ; 35(12): 2060-2065, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34096432

RESUMO

In this work was to develop an inedited nanocapsule with tucumã oil (Astrocaryum vulgare). The oil presents of phytosterols (squalene and ß-sitosterol), all-trans-beta-carotene, acids oleic and palmitic. Antioxidant activity showed a good performance in DPPH and ABTS assays. The nanocapsules were prepared and demonstrated in their characterization particle size (206 ± 0.69 nm). The cytogenotoxicity evaluation was performed using the MTT, dichlorofluorescein, nitric oxide and dsDNA PicoGreen® assays. Antitumor efficacy assays in MCF-7 cells demonstrated that free oil and tucumã nanocapsules had IC50 of 130 and 50 µg/mL, respectively. Thus, previous studies of toxicity are relevant, as they generate future subsidies, aiming at the potential application of nanostructures and in addition, the promising effect of NCs of tucumã oil on the antiproliferative effect in breast adenocarcinoma cells was evidenced.


Assuntos
Antioxidantes/farmacologia , Arecaceae/química , Nanocápsulas/química , Compostos Fitoquímicos/farmacologia , Óleos Vegetais/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/análise , Proliferação de Células/efeitos dos fármacos , Feminino , Humanos , Células MCF-7 , Tamanho da Partícula , Compostos Fitoquímicos/análise , Fitosteróis/análise , Óleos Vegetais/química
18.
Artigo em Inglês | MEDLINE | ID: mdl-34065031

RESUMO

COVID-19 has sparked a debate on the vulnerability of densely populated cities. Some studies argue that high-density urban centers are more vulnerable to infectious diseases due to a higher chance of infection in crowded urban environments. Other studies, however, argue that connectivity rather than population density plays a more significant role in the spread of COVID-19. While several studies have examined the role of urban density and connectivity in Europe and the U.S., few studies have been conducted in Asian countries. This study aims to investigate the role of urban spatial structure on COVID-19 by comparing different measures of urban density and connectivity during the first eight months of the outbreak in Korea. Two measures of density were derived from the Korean census, and four measures of connectivity were computed using social network analysis of the Origin-Destination data from the 2020 Korea Transport Database. We fitted both OLS and negative binomial models to the number of confirmed COVID-19 patients and its infection rates at the county level, collected individually from regional government websites in Korea. Results show that both density and connectivity play an important role in the proliferation of the COVID-19 outbreak in Korea. However, we found that the connectivity measure, particularly a measure of network centrality, was a better indicator of COVID-19 proliferation than the density measures. Our findings imply that policies that take into account different types of connectivity between cities might be necessary to contain the outbreak in the early phase.


Assuntos
COVID-19 , Ásia , Proliferação de Células , Cidades , Europa (Continente) , Humanos , República da Coreia/epidemiologia , SARS-CoV-2
19.
Magy Onkol ; 65(2): 157-166, 2021 Jun 03.
Artigo em Húngaro | MEDLINE | ID: mdl-34081763

RESUMO

Insufficient tissue perfusion in malignancies results in hypoxic areas, favoring neoplastic progression. Tumor cells under hypoxia undergo an adaptive program by activating alternative metabolic pathways, which is regulated by hypoxia inducible factor-1 (HIF1) in order to overcome microenvironmental changes. The expression of carbonic anhydrase IX (CAIX) is a prominent protective mechanism against intracellular acidosis occurring in cancer cells suffering from hypoxia. Due to the activity of CAIX, the restored intracellular pH (pHi) supports tumor cell proliferation and migration, while the compensatory extracellular acidosis contributes to immunoprotection and to chemo- and radioresistance. In vitro and animal model experiments showed that the chemotherapeutic efficiency could be significantly improved by the selective inhibition of CAIX, thus, its adjuvant therapeutic potential is under active investigation.


Assuntos
Antígenos de Neoplasias , Neoplasias , Animais , Anidrase Carbônica IX/metabolismo , Hipóxia Celular , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Neoplasias/tratamento farmacológico
20.
J Int Med Res ; 49(6): 3000605211018592, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34082605

RESUMO

OBJECTIVE: To explore the neddylation pathway, found to be highly activated in various cancers, as a potential therapeutic target in endometrial carcinoma, one of the three most frequent malignant tumours in the female reproductive system. METHODS: Data from The Cancer Genome Atlas were analysed using online servers. Expression levels of key neddylation genes were validated by reverse-transcription polymerase chain reaction and western blots of tumour and adjacent tissues. Underlying mechanisms and the effects on cell activities of the neddylation pathway-specific inhibitor, MLN4924, were investigated in endometrial cancer cell lines. RESULTS: Key neddylation enzymes, ubiquitin conjugating enzyme E2 M (UBC12), ubiquitin conjugating enzyme E2 F (UBE2F), ring-box 1 (RBX1) and ring finger protein 7 (RBX2), were significantly overexpressed in endometrial carcinoma tissues versus normal tissues, but only UBE2F and RBX2 positively correlated with patient survival. MLN4924 significantly suppressed proliferation and colony formation in EC cells by inducing DNA re-replication, cell cycle arrest and apoptosis. Mechanism study revealed that MLN4924 induced the accumulation of cullin-RING ligase substrates in vitro. CONCLUSIONS: The neddylation pathway was identified to play an important role in endometrial cancer. The neddylation specific inhibitor, MLN4924, may be a potential therapeutic drug for endometrial carcinoma.


Assuntos
Neoplasias do Endométrio , Ubiquitinas , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Ciclopentanos/farmacologia , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/genética , Feminino , Humanos , Proteína NEDD8/genética , Pirimidinas , Ubiquitinas/genética
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