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1.
Cell Commun Signal ; 22(1): 343, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38907279

RESUMEN

Mitochondria are central to endothelial cell activation and angiogenesis, with the RNA polymerase mitochondrial (POLRMT) serving as a key protein in regulating mitochondrial transcription and oxidative phosphorylation. In our study, we examined the impact of POLRMT on angiogenesis and found that its silencing or knockout (KO) in human umbilical vein endothelial cells (HUVECs) and other endothelial cells resulted in robust anti-angiogenic effects, impeding cell proliferation, migration, and capillary tube formation. Depletion of POLRMT led to impaired mitochondrial function, characterized by mitochondrial depolarization, oxidative stress, lipid oxidation, DNA damage, and reduced ATP production, along with significant apoptosis activation. Conversely, overexpressing POLRMT promoted angiogenic activity in the endothelial cells. In vivo experiments demonstrated that endothelial knockdown of POLRMT, by intravitreous injection of endothelial specific POLRMT shRNA adeno-associated virus, inhibited retinal angiogenesis. In addition, inhibiting POLRMT with a first-in-class inhibitor IMT1 exerted significant anti-angiogenic impact in vitro and in vivo. Significantly elevated expression of POLRMT was observed in the retinal tissues of streptozotocin-induced diabetic retinopathy (DR) mice. POLRMT endothelial knockdown inhibited pathological retinal angiogenesis and mitigated retinal ganglion cell (RGC) degeneration in DR mice. At last, POLRMT expression exhibited a substantial increase in the retinal proliferative membrane tissues of human DR patients. These findings collectively establish the indispensable role of POLRMT in angiogenesis, both in vitro and in vivo.


Asunto(s)
ARN Polimerasas Dirigidas por ADN , Células Endoteliales de la Vena Umbilical Humana , Mitocondrias , Humanos , Animales , Ratones , Mitocondrias/metabolismo , ARN Polimerasas Dirigidas por ADN/metabolismo , ARN Polimerasas Dirigidas por ADN/genética , Retinopatía Diabética/patología , Retinopatía Diabética/metabolismo , Retinopatía Diabética/genética , Ratones Endogámicos C57BL , Proliferación Celular , Neovascularización Patológica/genética , Neovascularización Patológica/metabolismo , Masculino , Neovascularización Fisiológica/genética , Movimiento Celular , Apoptosis , Angiogénesis
2.
Neural Plast ; 2021: 6636999, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33574837

RESUMEN

Hemiplegic gait is the most common sequela of stroke. Patients with hemiplegic gait are at a risk of falling because of poor balance. The theory of cognitive-motor networks paved the way for a new field of research. However, the mechanism of the relationship of cognition with gait or posture control networks is unclear because of the dynamic characteristics of walking and changing postures. To explore differences in the balance function and fall risk between patients with and without cognitive impairment after stroke, we utilized the Berg balance scale, Timed "Up and Go" test, and 10 m walking test. Patients were divided into two groups: the observation group (16 patients, female 6 and male 10), comprising patients with cognitive impairment after stroke, and the control group (16 patients, female 7 and male 9), comprising patients without cognitive impairment after stroke. We found that patients with cognitive impairment had worse balance function and a higher risk of falls. They needed a longer time to turn around or sit down. Our findings indicated that posture control in turning around and sitting down required more cognitive resources in daily life.


Asunto(s)
Cognición/fisiología , Trastornos Neurológicos de la Marcha/fisiopatología , Marcha/fisiología , Equilibrio Postural/fisiología , Accidente Cerebrovascular/fisiopatología , Adulto , Estudios de Casos y Controles , Femenino , Trastornos Neurológicos de la Marcha/etiología , Trastornos Neurológicos de la Marcha/psicología , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/psicología , Rehabilitación de Accidente Cerebrovascular
3.
Mol Cancer ; 16(1): 17, 2017 01 21.
Artículo en Inglés | MEDLINE | ID: mdl-28109288

RESUMEN

BACKGROUND: Numerous studies have shown that long non-coding RNAs (lncRNAs) behave as a novel class of transcript during multiple cancer processes, such as cell proliferation, apoptosis, migration, and invasion. LINC00152 is located on chromosome 2p11.2, and has a transcript length of 828 nucleotides. The biological role of LINC00152 in LAD(lung adenocarcinoma) remains unknown. METHODS: Quantitative reverse transcription PCR(qRT-PCR) was used to detect LINC00152 expression in 60 human LAD tissues and paired normal tissues. In vitro and in vivo studies showed the biological function of LINC00152 in tumour progression. RNA transcriptome sequencing technology was performed to identify the downstream suppressor IL24(interleukin 24) which was further examined by qRT-PCR, western bolt and rescue experiments. RNA immunoprecipitation (RIP), RNA pulldown, and Chromatin immunoprecipitation (ChIP) assays were carried out to reveal the interaction between LINC00152, EZH2 and IL24. RESULTS: LINC00152 expression was upregulated in 60 human LAD tissues and paired normal tissues. High levels of LINC00152 expression were correlated with advanced TNM stage, larger tumor size, and lymph node metastasis, as well as shorter survival time. Silencing of LINC00152 suppressed cell growth and induced cell apoptosis. LINC00152 knockdown altered the expression of many downstream genes, including IL24. LINC00152 could interact with EZH2 and inhibit IL24 transcription. Moreover, the ectopic expression of IL24 repressed cell proliferation and partly reversed LINC00152 overexpression-induced promotion of cell growth in LAD. CONCLUSIONS: Our study reveals an oncogenic role for LINC00152 in LAD tumorigenesis, suggesting that it could be used as a therapeutic target in LAD treatment.


Asunto(s)
Adenocarcinoma/genética , Proteína Potenciadora del Homólogo Zeste 2/genética , Regulación Neoplásica de la Expresión Génica , Interleucinas/genética , Neoplasias Pulmonares/genética , ARN Largo no Codificante/genética , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adenocarcinoma del Pulmón , Anciano , Anciano de 80 o más Años , Animales , Apoptosis/genética , Línea Celular Tumoral , Proliferación Celular , Transformación Celular Neoplásica/genética , Análisis por Conglomerados , Biología Computacional/métodos , Modelos Animales de Enfermedad , Expresión Génica Ectópica , Femenino , Puntos de Control de la Fase G1 del Ciclo Celular/genética , Perfilación de la Expresión Génica , Silenciador del Gen , Histona Demetilasas/genética , Humanos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Ratones , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , Interferencia de ARN , Carga Tumoral
4.
Tumour Biol ; 2016 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-27752997

RESUMEN

MicroRNAs are a large group of non-coding RNAs that have emerged as regulators of various biological processes, especially carcinogenesis and cancer progression. Recent evidence has shown that microRNA-196a (miR-196a) is upregulated in most types of tumors and involved in multiple biological processes via translational inhibition and mRNA cleavage, such as cell proliferation, migration, and invasion, mostly functioning as an oncogene. Dysregulation of miR-196a promotes oncogenesis and tumor progression. In this review, we summarize the upstream regulators, target genes, signaling pathways, and single nucleotide polymorphisms of miR-196a, which collectively affect cell proliferation, migration, and invasion. In addition, we review the clinical outcomes and significance of miR-196a. miR-196a may serve as a novel biomarker or target for diagnosis, prognosis, and therapy in several human cancers.

5.
Eur J Nutr ; 55(2): 809-813, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25869181

RESUMEN

PURPOSE: Thinness in children and adolescents poses a considerable public health problem globally, especially in developing countries. The present study examined the prevalence of thinness among children and adolescents in Shandong, China. METHODS: Data for this study were obtained from a large cross-sectional survey of schoolchildren. A total of 42,348 students (21,248 boys and 21,100 girls) aged 7-18 years participated in this study. Stature and weight of all subjects were measured; body mass index (BMI) was calculated from their stature and weight. International BMI cutoffs were used to define thinness. RESULTS: The overall prevalences of thinness grade 1, grade 2 and grade 3 among children and adolescents aged 7-18 years were 7.74, 1.43 and 0.61 % for boys and 11.51, 2.54 and 1.03 % for girls, respectively; these figures were all significantly higher in girls than in boys (P < 0.01). Thin children and adolescents had lower stature levels than their counterparts in not thin group in all age groups (7-18 years). CONCLUSION: The prevalence of childhood thinness is still wide in Shandong Province, and public health and nutritional strategies must give attention to the intervention for thinness, including periodic monitoring, education on pattern of nutrition and healthy dietary behavior.


Asunto(s)
Delgadez/epidemiología , Adolescente , Estatura , Índice de Masa Corporal , Peso Corporal , Niño , China/epidemiología , Estudios Transversales , Femenino , Humanos , Masculino , Prevalencia , Salud Pública , Encuestas y Cuestionarios
6.
J Trop Pediatr ; 62(4): 293-300, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-26966244

RESUMEN

BACKGROUND: The pattern of urban-rural disparity in childhood obesity varies across countries. The present study examined the change trend of urban-rural disparity in childhood overweight and obesity from 1985 to 2014 in Shandong, China. METHODS: Data for this study were obtained from four cross-sectional surveys of school children carried out in 1985, 1995, 2005 and 2014 in Shandong Province, China. In this study, 39 943 students aged 7-18 years were included (14 458 in 1985, 7198 in 1995, 8568 in 2005 and 9719 in 2014). Height and weight of all subjects were measured; body mass index (BMI) was calculated from their height and weight. The BMI cutoff points recommended by the International Obesity Task Force were used to define overweight and obesity. RESULTS: The prevalence of overweight and obesity was increasing continuously both in urban and rural areas over the past 29 years (1985-2014). The prevalence of combined overweight and obesity was significantly higher in urban than in rural children and adolescents in 1985, 1995 and 2005 (p < 0.01). However, a rapid increase in the prevalence of combined overweight and obesity was observed in rural areas after 2005; as a result, the urban-rural disparity was getting narrower, and no significant urban-rural disparity was observed in 2014 (p > 0.05). CONCLUSION: The change trend of urban-rural disparity should be concerned in the future; policies and interventions focused on childhood overweight and obesity should pay attention to rural areas.


Asunto(s)
Disparidades en el Estado de Salud , Obesidad Abdominal/epidemiología , Sobrepeso/epidemiología , Obesidad Infantil/epidemiología , Adolescente , Índice de Masa Corporal , Niño , China/epidemiología , Estudios Transversales , Femenino , Humanos , Masculino , Prevalencia , Características de la Residencia , Población Rural , Población Urbana
7.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 36(4): 480-3, 2016 Apr.
Artículo en Zh | MEDLINE | ID: mdl-27323624

RESUMEN

The gene types of breast cancer can be classified into three types according to its molecules: Luminal type A, Luminal type B, HER-2-positive type, triple negative type. Authors combined pathological characteristics of breast cancer, biological characteristics, and comprehensive treatment, used syndrome typing based medication, and explored treatment meticulous ideas and methods of "treating the same disease with different methods" as well as "different treatment methods in accordance with patients individually".


Asunto(s)
Neoplasias de la Mama/clasificación , Neoplasias de la Mama/genética , Neoplasias de la Mama/terapia , Biomarcadores de Tumor/genética , Femenino , Humanos , Receptor ErbB-2/genética
8.
Mol Cancer ; 14: 82, 2015 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-25890171

RESUMEN

BACKGROUND: Mounting evidence indicates that long noncoding RNAs (lncRNAs) could play a pivotal role in cancer biology. However, the overall biological role and clinical significance of PVT1 in gastric carcinogenesis remains largely unknown. METHODS: Expression of PVT1 was analyzed in 80 GC tissues and cell lines by qRT-PCR. The effect of PVT1 on proliferation was evaluated by MTT and colony formation assays, and cell apoptosis was evaluated by Flow-cytometric analysis. GC cells transfected with shPVT1 were injected into nude mice to study the effect of PVT1 on tumorigenesis in vivo. RIP was performed to confirm the interaction between PVT1 and EZH2. ChIP was used to study the promoter region of related genes. RESULTS: The higher expression of PVT1 was significantly correlated with deeper invasion depth and advanced TNM stage. Multivariate analyses revealed that PVT1 expression served as an independent predictor for overall survival (p = 0.031). Further experiments demonstrated that PVT1 knockdown significantly inhibited the proliferation both in vitro and in vivo. Importantly, we also showed that PVT1 played a key role in G1 arrest. Moreover, we further confirmed that PVT1 was associated with enhancer of zeste homolog 2 (EZH2) and that this association was required for the repression of p15 and p16. To our knowledge, this is the first report showed that the role and the mechanism of PVT1 in the progression of gastric cancer. CONCLUSIONS: Together, these results suggest that lncRNA PVT1 may serve as a candidate prognostic biomarker and target for new therapies in human gastric cancer.


Asunto(s)
Proliferación Celular/genética , Inhibidor p15 de las Quinasas Dependientes de la Ciclina/genética , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , ARN Largo no Codificante/genética , Neoplasias Gástricas/genética , Animales , Apoptosis/genética , Biomarcadores de Tumor/genética , Carcinogénesis/genética , Línea Celular , Línea Celular Tumoral , Proteína Potenciadora del Homólogo Zeste 2 , Epigenómica/métodos , Puntos de Control de la Fase G1 del Ciclo Celular/genética , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Complejo Represivo Polycomb 2/genética , Pronóstico , Regiones Promotoras Genéticas/genética , Transfección/métodos
9.
Tumour Biol ; 36(3): 1403-9, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25740059

RESUMEN

MicroRNAs (miRNAs) are small non-coding RNAs that function by base pairing with messenger RNAs, thereby regulating protein expression. Functional studies indicate that miRNAs are involved in the regulation of almost every biological pathway. Moreover, changes in miRNA expression are associated with several human pathologies, including cancer. Dysregulation and aberrant expression of microRNA-100 (miR-100) have been reported to be involved in tumorigenesis and tumor progression of several cancer types, suggesting that miR-100 might serve as a diagnostic and/or prognostic marker for human malignancy. In this review, we summarize the potential application of miR-100 in cancer treatment and as a new molecular marker for cancer prognosis and diagnosis. We will provide a brief introduction to miR-100 and discuss its role as a non-invasive biomarker and a potential therapeutic target in human cancers.


Asunto(s)
MicroARNs/genética , Neoplasias/diagnóstico , Neoplasias/genética , Antineoplásicos/uso terapéutico , Biomarcadores de Tumor/genética , Humanos , Neoplasias/tratamiento farmacológico , Pronóstico
10.
Tumour Biol ; 36(7): 5341-51, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25672609

RESUMEN

SUZ12 is a core component of the polycomb repressive complex 2 (PRC2), which could silence gene transcription by generating trimethylation on lysine 27 residue of histone H3 (H3K27Me3). Meanwhile, SUZ12 has been found to be overexpressed in multiple cancers; however, the clinical significance and molecular mechanisms of SUZ12 controlling gastric cancer cell proliferation and metastasis are unclear. In this study, we found that SUZ12 expression was significantly increased in 64 gastric tumor tissues compared with normal tissues. Additionally, SUZ12 expression was associated with pathological stage, metastasis distance, and shorter overall survival of gastric cancer patients. Knockdown of SUZ12 expression impaired cell proliferation and invasion in vitro, leading to the inhibition of metastasis in vivo. Upregulation of SUZ12 was found to play a key role in gastric cancer cell proliferation and metastasis through the regulation of EMT and KLF2 expression.


Asunto(s)
Cadherinas/biosíntesis , Factores de Transcripción de Tipo Kruppel/biosíntesis , Complejo Represivo Polycomb 2/genética , Neoplasias Gástricas/genética , Adulto , Anciano , Animales , Cadherinas/genética , Línea Celular Tumoral , Proliferación Celular/genética , Transición Epitelial-Mesenquimal/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Factores de Transcripción de Tipo Kruppel/genética , Masculino , Ratones , Persona de Mediana Edad , Invasividad Neoplásica/genética , Metástasis de la Neoplasia , Proteínas de Neoplasias , Estadificación de Neoplasias , Complejo Represivo Polycomb 2/biosíntesis , Neoplasias Gástricas/patología , Factores de Transcripción , Ensayos Antitumor por Modelo de Xenoinjerto
11.
Beijing Da Xue Xue Bao Yi Xue Ban ; 47(5): 796-9, 2015 Oct 18.
Artículo en Zh | MEDLINE | ID: mdl-26474618

RESUMEN

OBJECTIVE: To evaluate the endothelial functions and autoregulation capacity of cerebral blood flow in patients with Fabry disease. METHODS: Brachial artery vasodilation was assessed in 8 patients with Fabry disease and 14 healthy controls by means of flow-mediated dilation (FMD) and Nitroglycerin-mediated dilation (NMD). Cerebrovascular reactivity was calculated in terms of breath-holding index (BHI) and vascular motor reactivity (VMR) by TCD-CO2 test in 4 patients and 14 healthy controls. RESULTS: Compared with the controls, brachial artery vasodilation experiment showed no difference (the patients: FMD 15.94%±5.03% and NMD 23.92%±7.23%, the controls: FMD 14.57%±5.84% and NMD 22.64%±6.96%), there was no relationship between FMD or NMD and the age, course of disease, MSSI or enzyme activity. In respect of cerebrovascular autoregulation capacity, there was no difference in anterior circulation, while cerebrovascular reactivity tended to be impaired in posterior circulation. CONCLUSION: Endothelial function showed no decline in patients with Fabry disease, but cerebrovascular autoregulation capacity tended to be impaired in posterior circulation.


Asunto(s)
Endotelio Vascular/fisiopatología , Enfermedad de Fabry/fisiopatología , Vasodilatación , Arteria Braquial , Estudios de Casos y Controles , Humanos , Nitroglicerina , Factores de Riesgo
12.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 35(7): 866-70, 2015 Jul.
Artículo en Zh | MEDLINE | ID: mdl-26380452

RESUMEN

OBJECTIVE: To observe enhanced effects of polypeptide extract from scorpion venom (PESV) combined Rapamycin on autophagy of H22 hepatoma cells in mice and to explore its possible mechanism. METHODS: The H22 hepatocarcinoma cell suspension was subcutaneously inoculated into 40 Kunming mice. Then tumor-bearing mice were randomly divided into four groups, i.e., the control group,the high dose PESV group, the low dose PESV group, and the combination group (high dose PESV + Rapamycin), 10 in each group. Mice in high and dose PESV groups were administered with 20 mg/kg and 10 mg/kg PESV respectively by gastrogavage. Mice in the combination group were administered with 2 mg/kg rapamycin and 20 mg/kg PESV by gastrogavage. The intervention lasted for 14 successive days. The tumor volume was measured once every other day, the tumor growth curve was drawn, and then the tumor inhibitory rate calculated. Pathological changes of the tumor tissue were observed by HE staining. Protein expression levels of mammal target of rapamycin (mTOR), UNC-51-like kinase-1 (ULK1), microtubule-associated protein1 light chain3 (MAPILC3A), and Beclin1 were detected by immunohistochemical assay. RESULTS: The growth of H22 hepatoma transplantation tumor was inhibited in high and low dose PESV groups and the combination group (P < 0.05). And there was statistical difference in tumor weight and tumor volume between the combination group and high and low dose PESV groups (P < 0.05). There was no statistical difference in tumor weight or tumor volume between the high dose PESV group and the low dose PESV group (P > 0.05). lmmunohistochemical assay showed that the protein expression of mTOR was higher, but protein expressions of ULK1, MAP1LC3A, Beclin1 were lower in the control group than in the rest 3 groups (P < 0.05, P < 0.01). Compared with the high dose PESV group, protein expressions of ULK1, MAP1LC3A, and Beclin1 were obviously lower (P < 0.05). CONCLUSION: PESV combined Rapamycin might inhibit the development of H22 hepatoma transplantation tumor in mice possibly through inhibiting the activity of mTOR, enhancing expressions of ULK1, MAP1LC3A, and Beclin1.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Venenos de Escorpión/farmacología , Sirolimus/farmacología , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Autofagia/efectos de los fármacos , Carcinoma Hepatocelular , Línea Celular Tumoral , Neoplasias Hepáticas , Ratones , Trasplante de Neoplasias , Péptidos , Venenos de Escorpión/uso terapéutico , Sirolimus/uso terapéutico
13.
Mol Cancer ; 13: 68, 2014 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-24655544

RESUMEN

BACKGROUND: Recent evidence indicates that long noncoding RNAs (lncRNAs) play a critical role in the regulation of cellular processes, such as differentiation, proliferation and metastasis. These lncRNAs are found to be dysregulated in a variety of cancers. BRAF activated non-coding RNA (BANCR) is a 693-bp transcript on chromosome 9 with a potential functional role in melanoma cell migration. The clinical significance of BANCR, and its' molecular mechanisms controlling cancer cell migration and metastasis are unclear. METHODS: Expression of BANCR was analyzed in 113 non-small cell lung cancer (NSCLC) tissues and seven NSCLC cell lines using quantitative polymerase chain reaction (qPCR) assays. Gain and loss of function approaches were used to investigate the biological role of BANCR in NSCLC cells. The effects of BANCR on cell viability were evaluated by MTT and colony formation assays. Apoptosis was evaluated by Hoechst staining and flow cytometry. Nude mice were used to examine the effects of BANCR on tumor cell metastasis in vivo. Protein levels of BANCR targets were determined by western blotting and fluorescent immunohistochemistry. RESULTS: BANCR expression was significantly decreased in 113 NSCLC tumor tissues compared with normal tissues. Additionally, reduced BANCR expression was associated with larger tumor size, advanced pathological stage, metastasis distance, and shorter overall survival of NSCLC patients. Reduced BANCR expression was found to be an independent prognostic factor for NSCLC. Histone deacetylation was involved in the downregulation of BANCR in NSCLC cells. Ectopic expression of BANCR impaired cell viability and invasion, leading to the inhibition of metastasis in vitro and in vivo. However, knockdown of BANCR expression promoted cell migration and invasion in vitro. Overexpression of BANCR was found to play a key role in epithelial-mesenchymal transition (EMT) through the regulation of E-cadherin, N-cadherin and Vimentin expression. CONCLUSION: We determined that BANCR actively functions as a regulator of EMT during NSCLC metastasis, suggesting that BANCR could be a biomarker for poor prognosis of NSCLC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Transición Epitelial-Mesenquimal/fisiología , Neoplasias Pulmonares/metabolismo , Proteínas Proto-Oncogénicas B-raf/biosíntesis , ARN Largo no Codificante/biosíntesis , Animales , Apoptosis/genética , Western Blotting , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Movimiento Celular/fisiología , Regulación hacia Abajo , Citometría de Flujo , Xenoinjertos , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidad , Masculino , Ratones , Ratones Desnudos , Invasividad Neoplásica/genética , Pronóstico , Proteínas Proto-Oncogénicas B-raf/genética , ARN Largo no Codificante/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
14.
Mol Cancer ; 13: 92, 2014 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-24775712

RESUMEN

BACKGROUND: Accumulating evidence indicates that the long non-coding RNA HOTAIR plays a critical role in cancer progression and metastasis. However, the overall biological role and clinical significance of HOTAIR in gastric carcinogenesis remains largely unknown. METHODS: HOTAIR expression was measured in 78 paired cancerous and noncancerous tissue samples by real-time PCR. The effects of HOTAIR on gastric cancer cells were studied by overexpression and RNA interference approaches in vitro and in vivo. Insights of the mechanism of competitive endogenous RNAs (ceRNAs) were gained from bioinformatic analysis, luciferase assays and RNA binding protein immunoprecipitation (RIP). The positive HOTAIR/HER2 interaction was identified and verified by immunohistochemistry assay and bivariate correlation analysis. RESULTS: HOTAIR upregulation was associated with larger tumor size, advanced pathological stage and extensive metastasis, and also correlated with shorter overall survival of gastric cancer patients. Furthermore, HOTAIR overexpression promoted the proliferation, migration and invasion of gastric carcinoma cells, while HOTAIR depletion inhibited both cell invasion and cell viability, and induced growth arrest in vitro and in vivo. In particular, HOTAIR may act as a ceRNA, effectively becoming a sink for miR-331-3p, thereby modulating the derepression of HER2 and imposing an additional level of post-transcriptional regulation. Finally, the positive HOTAIR/HER2 correlation was significantly associated with advanced gastric cancers. CONCLUSIONS: HOTAIR overexpression represents a biomarker of poor prognosis in gastric cancer, and may confer malignant phenotype to tumor cells. The ceRNA regulatory network involving HOTAIR and the positive interaction between HOTAIR and HER2 may contribute to a better understanding of gastric cancer pathogenesis and facilitate the development of lncRNA-directed diagnostics and therapeutics against this disease.


Asunto(s)
Biomarcadores de Tumor/genética , Carcinoma/genética , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , ARN Largo no Codificante/genética , Receptor ErbB-2/genética , Neoplasias Gástricas/genética , Animales , Secuencia de Bases , Biomarcadores de Tumor/metabolismo , Carcinoma/metabolismo , Carcinoma/mortalidad , Carcinoma/patología , Proliferación Celular , Supervivencia Celular , Femenino , Humanos , Metástasis Linfática , Masculino , Ratones , Ratones Desnudos , MicroARNs/metabolismo , Datos de Secuencia Molecular , Trasplante de Neoplasias , ARN Largo no Codificante/metabolismo , Receptor ErbB-2/metabolismo , Transducción de Señal , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Análisis de Supervivencia , Microambiente Tumoral
15.
Beijing Da Xue Xue Bao Yi Xue Ban ; 46(4): 646-9, 2014 Aug 18.
Artículo en Zh | MEDLINE | ID: mdl-25131487

RESUMEN

OBJECTIVE: To report a case of leucine-rich glioma inactivated-1 protein antibody (LGI1-Ab) associated limbic encephalitis. METHODS: A 76-year-old woman was admitted to the hospital because of cognitive impairment and faciobrachial dystonic seizures for six months. Hyponatremia was also noted in this patient. Antibodies to the LGI1 were positive.(18)F-FDG uptake was measured on the PET-CT scans of this patient. RESULTS: PET-CT showed bilateral putamen hypermetabolism with hypometabolism in other regions. Her symptoms were improved after intravenous immunoglobulin therapy. CONCLUSION: LGI1-Ab associated encephalitis can manifest as basal ganglia hypermetabolism and faciobrachial dystonic seizures.


Asunto(s)
Anticuerpos/sangre , Encefalitis Límbica/inmunología , Proteínas/inmunología , Anciano , Trastornos del Conocimiento/etiología , Femenino , Glioma , Humanos , Péptidos y Proteínas de Señalización Intracelular , Encefalitis Límbica/complicaciones , Convulsiones/etiología
16.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 34(5): 581-6, 2014 May.
Artículo en Zh | MEDLINE | ID: mdl-24941848

RESUMEN

OBJECTIVE: To explore the mechanism of polypeptide extract from scorpion venom (PESV) on inhibiting angiogenesis. METHODS: The H22 hepatoma tumor model was established by subcutaneously implanting H22 hepatoma cells into mice. The tumor-bearing mice were randomly divided into 4 groups, i.e., the control group, the high dose PESV group, the low dose PESV group, and the 5-fluorouracil (5-Fu) group, 10 mice in each group. The intervention was lasted for 14 days. The growth curve of the tumor volume was drawn and the inhibition rate calculated. Pathological changes of the tumors were observed by HE staining. The microvessel density (MVD) was detected using SP method. The protein expression levels of phosphatidylinositol 3-kinase (P13K), phosphoprotein kinase B (P-Akt), hypoxia-inducible factor-1 alpha (HIF-1 )alpha, and vascular endothelial growth factor-A (VEGF-A) were detected by immunohistochemical assay and Western blot. RESULTS: The tumor inhibitory rate was 64.8%, 43.7%, and 32.4% in the 5-Fu group, the high dose PESV group, and the low dose PESV group. Compared with the control group, the protein expression of PI3K, P-Akt, HIF-1alpha, and VEGF-A were obviously inhibited by PESV and 5-Fu (P <0. 05,P <0. 01). The MVD also decreased in the high and low dose PESV groups (P < 0.05). CONCLUSIONS: PESV could inhibit the angiogenesis of H22 hepatoma. The mechanisms might be associated with suppressing the expression of PI3K, P-Akt, HIF-1 alpha, and VEGF-A.


Asunto(s)
Inhibidores de la Angiogénesis/farmacología , Venenos de Escorpión/farmacología , Animales , Línea Celular Tumoral , Fluorouracilo/farmacología , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Neoplasias Hepáticas , Masculino , Ratones , Péptidos/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Factor A de Crecimiento Endotelial Vascular
17.
BMC Cancer ; 13: 464, 2013 Oct 08.
Artículo en Inglés | MEDLINE | ID: mdl-24103700

RESUMEN

BACKGROUND: The identification of cancer-associated long non-coding RNAs and the investigation of their molecular and biological functions are important for understanding the molecular biology and progression of cancer. HOTAIR (HOX transcript antisense intergenic RNA) has been implicated in several cancers; however, its role in non-small cell lung cancer (NSCLC) is unknown. The aim of the present study was to examine the expression pattern of HOTAIR in NSCLC and to evaluate its biological role and clinical significance in tumor progression. METHODS: Expression of HOTAIR was analyzed in 42 NSCLC tissues and four NSCLC cell lines by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Over-expression and RNA interference (RNAi) approaches were used to investigate the biological functions of HOTAIR. The effect of HOTAIR on proliferation was evaluated by MTT and colony formation assays, and cell migration and invasion were evaluated by transwell assays. Tail vein injection of cells was used to study metastasis in nude mice. Protein levels of HOTAIR targets were determined by western blot analysis. Differences between groups were tested for significance using Student's t-test (two-tailed). RESULTS: HOTAIR was highly expressed both in NSCLC samples and cell lines compared with corresponding normal counterparts. HOTAIR upregulation was correlated with NSCLC advanced pathological stage and lymph-node metastasis. Moreover, patients with high levels of HOTAIR expression had a relatively poor prognosis. Inhibition of HOTAIR by RNAi decreased the migration and invasion of NSCLC cells in vitro and impeded cell metastasis in vivo. HOXA5 levels were affected by HOTAIR knockdown or over-expression in vitro. CONCLUSIONS: Our findings indicate that HOTAIR is significantly up-regulated in NSCLC tissues, and regulates NSCLC cell invasion and metastasis, partially via the down-regulation of HOXA5. Thus, HOTAIR may represent a new marker of poor prognosis and is a potential therapeutic target for NSCLC intervention.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , ARN Largo no Codificante/genética , Apoptosis/genética , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular , Femenino , Regulación Neoplásica de la Expresión Génica , Proteínas de Homeodominio/metabolismo , Humanos , Neoplasias Pulmonares/mortalidad , Masculino , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Clasificación del Tumor , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico
18.
Mol Cell Biochem ; 372(1-2): 35-45, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-22956424

RESUMEN

MicroRNAs (miRNAs) regulate gene expression by binding to target sites and initiating translational repression and/or mRNA degradation. In our previous study, we have shown that expression of serum microRNA (miR)-21 is correlated with TNM stage and lymph node metastasis and might be an independent prognostic factor for NSCLC patients. However, the roles of miR-21 overexpression in NSCLC development are still unclear. The purpose of this study is to investigate the effect of miR-21 and determine whether miR-21 can be a therapeutic target for human NSCLC. Taqman real-time quantitative RT-PCR assay was performed to detect miR-21 expression in NSCLC cell lines and tissues. Next, the effects of miR-21 expression on NSCLC cell characteristics including growth, invasion, and chemo- or radioresistance were also determined. Results showed that miR-21 is commonly upregulated in NSCLC cell lines and tissues with important functional consequences. In addition, we found that anti-miR-21 could significantly inhibit growth, migration and invasion, and reverse chemo- or radioresistance of NSCLC cells, while miR-21 mimics could increase growth, promote migration and invasion, and enhance chemo- or radioresistance of NSCLC cells. Meanwhile, miR-21 mimics could inhibit expression of PTEN mRNA and protein and the luciferase activity of a PTEN 3'-untranslated region (UTR)-based reporter construct in A549 cells, while anti-miR-21 could increase expression of PTEN mRNA and protein and the luciferase activity of a PTEN 3'-UTR-based reporter construct in A549 cells. Furthermore, overexpression of PTEN could mimic the same effects of anti-miR-21 in NSCLC cells, and siRNA-mediated downregulation of PTEN could rescue the effects on NSCLC cells induced by anti-miR-21. Taken together, these results provide evidence to show the promotion role of miR-21 in NSCLC development through modulation of the PTEN signaling pathway.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/secundario , Movimiento Celular , Proliferación Celular , Neoplasias Pulmonares/patología , MicroARNs/genética , Fosfohidrolasa PTEN/genética , Regiones no Traducidas 3' , Antineoplásicos/farmacología , Secuencia de Bases , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Estudios de Casos y Controles , Línea Celular Tumoral , Cisplatino/farmacología , Docetaxel , Resistencia a Antineoplásicos , Expresión Génica , Humanos , Concentración 50 Inhibidora , Neoplasias Pulmonares/metabolismo , Metástasis Linfática , MicroARNs/metabolismo , Invasividad Neoplásica , Fosfohidrolasa PTEN/metabolismo , Interferencia de ARN , Tolerancia a Radiación , Transducción de Señal , Taxoides/farmacología , Regulación hacia Arriba
19.
J Ultrasound Med ; 32(2): 361-3, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23341395

RESUMEN

Grains embedded as vaginal foreign bodies sometime occur in Chinese children. We summarized the sonographic characteristics of vaginal grains in 4 Chinese children and retrospectively analyzed the clinical data. Abdominal sonography can be the first choice for diagnosis of vaginal grains because of its noninvasive nature, high specificity, and low cost.


Asunto(s)
Cuerpos Extraños/diagnóstico por imagen , Vagina/diagnóstico por imagen , Preescolar , Femenino , Humanos , Lactante , Estudios Retrospectivos , Sensibilidad y Especificidad , Ultrasonografía
20.
Zhonghua Yi Xue Za Zhi ; 93(7): 508-11, 2013 Feb 19.
Artículo en Zh | MEDLINE | ID: mdl-23660318

RESUMEN

OBJECTIVE: To explore the relationship between muscular impairment rating scale (MIRS) and myopathological changes of myotonic dystrophy type 1 (DM1). METHODS: A total of 46 patients at our hospital from May 2003 to June 2011 were diagnosed as DM1. There were 30 males and 16 females. The age of onset ranged from 10 to 57 years old. The major symptoms included distal extremity weakness and myotonia. They were assessed with MIRS and muscle biopsies. The relationship was examined between MIRS and the variation of fiber size, central nuclear, ragged red fibers, proliferation of connective tissue, sarcoplasmic mass. Statistic analysis of pathological changes was made between the groups of MIRS ≥ 4 and ≤ 3. RESULTS: The scores of MIRS were 2 (n = 8), 3 (n = 14), 4 (n = 23) and 5 (n = 1). MIRS had significant correlations with variations of fiber size (P = 0.039, r = 0.305), degree of nuclear translocation (P = 0.002, r = 0.451) and ragged red fibers (P = 0.013, r = 0.364). But there was no significant correlation with the proliferation of connective tissue and sarcoplasmic mass. There were significant differences in nuclear translocation and ragged red fibers. But no significant difference existed in variations of fiber size between the groups of MIRS ≥ 4 and ≤ 3. CONCLUSION: The rating scale of MIRS has a certain myopathological basis, especially with regards to the changes in nuclear translocation and ragged red fibers.


Asunto(s)
Músculo Esquelético/patología , Distrofia Miotónica/patología , Adolescente , Adulto , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Adulto Joven
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