RESUMEN

BACKGROUND: Chromosome gains or localized amplifications are frequently observed in human gastric cancer (GC) and are major causes of aberrant oncogene activation. However, the significance of long non-coding RNAs (LncRNAs) in the above process is largely unknown. METHODS: The copy number aberrations (CNAs) data of GC samples were downloaded and analyzed from the TCGA database. qRT-PCR and fluorescence in situ hybridization were used to evaluate the expression of Linc01711 in GC. The effects of Linc01711 on GC progression were investigated through in vitro and in vivo assays. The mechanism of Linc01711 action was explored through transcriptome sequencing, chromatin immunoprecipitation sequencing, RNA immunoprecipitation, RNA pull-down and chromatin isolation by RNA purification (ChIRP) assays. RESULTS: We report for the first time a novel DNA copy number amplification-driven LncRNA on chromosome 20q13, designated Linc01711 in human GC, which is highly associated with malignant features. Functionally, Linc01711 significantly accelerates the proliferation and metastasis of GC. Mechanistically, Linc01711 acts as a modular scaffold to promote the binding of histone acetyltransferase HBO1 and histone demethylase KDM9. By coordinating the localization of the HBO1/KDM9 complex, Linc01711 specifies the histone modification pattern on the target genes, such as LPCAT1, and consequently facilitates the cholesterol synthesis, thereby contributing to tumor progression. CONCLUSIONS: Our findings suggest that copy number amplification-driven Linc01711 may serve as a promising prognostic predictor for GC patients and targeting Linc01711-related cholesterol metabolism pathway may be meaningful in anticancer strategies.

Asunto(s)

Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patología , Variaciones en el Número de Copia de ADN , Código de Histonas , Hibridación Fluorescente in Situ , Línea Celular Tumoral , ARN , Colesterol , Regulación Neoplásica de la Expresión Génica , Proliferación Celular/genética

RESUMEN

Primer is widely used to prepare bonding of chlorinated poly(vinyl chloride) (CPVC) pipe. The study examined the influences of primer and its major component, acetone, on CPVC's mechanical properties. Two types of CPVC product, sheet and pipe, were used in the mechanical testing. Sheet specimens were immersed in acetone or primer for 40 and 10 min, respectively, i.e., the maximum allowable time without mass loss, and then dried in air before the mechanical testing. Pipe (ring) specimens were treated either through immersion in acetone or primer for 30 min or in contact with these solvents locally on the inner surface for 2.5 h, and then air dried for 10.5 days before the mechanical testing. Results showed that CPVC's strength decreased after the absorption of these solvents, and air dry could remove acetone but not completely primer. The study also showed that pipe specimens by local contact with primer could generate brittle fracture. In view that sheet specimens always fractured in a ductile manner, brittle fracture of the pipe specimens could not be caused by CPVC degradation. Rather, strength decrease in the local region could provide a plausible explanation for the brittle fracture behavior, though further investigation is needed.

RESUMEN

Bile acid reflux and subsequent caudal-related homeobox 2 (CDX2) activation contribute to gastric intestinal metaplasia (IM), a precursor of gastric cancer; however, the mechanism underlying this phenomenon is unclear. Here, we demonstrate that alkylation repair homolog protein 5 (ALKBH5), a major RNA N6-adenosine demethylase, is required for bile acid-induced gastric IM. Mechanistically, we revealed the N6-methyladenosine (m6A) modification profile in gastric IM for the first time and identified ZNF333 as a novel m6A target of ALKBH5. ALKBH5 was shown to demethylate ZNF333 mRNA, leading to enhanced ZNF333 expression by abolishing m6A-YTHDF2-dependent mRNA degradation. In addition, ALKBH5 activated CDX2 and downstream intestinal markers by targeting the ZNF333/CYLD axis and activating NF-κB signaling. Reciprocally, p65, the key transcription factor of the canonical NF-κB pathway, enhanced the transcription activity of ALKBH5 in the nucleus, thus forming a positive feedforward circuit. Furthermore, ALKBH5 levels were positively correlated with ZNF333 and CDX2 levels in IM tissues, indicating significant clinical relevance. Collectively, our findings suggest that an m6A modification-associated positive feedforward loop between ALKBH5 and NF-κB signaling is involved in generating the IM phenotype of gastric epithelial cells. Targeting the ALKBH5/ZNF333/CYLD/CDX2 axis may be a useful therapeutic strategy for gastric IM in patients with bile regurgitation.

RESUMEN

BACKGROUND: As one of the most frequent chemical modifications in eukaryotic mRNAs, N6-methyladenosine (m6A) modification exerts important effects on mRNA stability, splicing, and translation. Recently, the regulatory role of m6A in tumorigenesis has been increasingly recognized. However, dysregulation of m6A and its functions in tumor epithelial-mesenchymal transition (EMT) and metastasis remain obscure. METHODS: qRT-PCR and immunohistochemistry were used to evaluate the expression of methyltransferase-like 3 (METTL3) in gastric cancer (GC). The effects of METTL3 on GC metastasis were investigated through in vitro and in vivo assays. The mechanism of METTL3 action was explored through transcriptome-sequencing, m6A-sequencing, m6A methylated RNA immunoprecipitation quantitative reverse transcription polymerase chain reaction (MeRIP qRT-PCR), confocal immunofluorescent assay, luciferase reporter assay, co-immunoprecipitation, RNA immunoprecipitation and chromatin immunoprecipitation assay. RESULTS: Here, we show that METTL3, a major RNA N6-adenosine methyltransferase, was upregulated in GC. Clinically, elevated METTL3 level was predictive of poor prognosis. Functionally, we found that METTL3 was required for the EMT process in vitro and for metastasis in vivo. Mechanistically, we unveiled the METTL3-mediated m6A modification profile in GC cells for the first time and identified zinc finger MYM-type containing 1 (ZMYM1) as a bona fide m6A target of METTL3. The m6A modification of ZMYM1 mRNA by METTL3 enhanced its stability relying on the "reader" protein HuR (also known as ELAVL1) dependent pathway. In addition, ZMYM1 bound to and mediated the repression of E-cadherin promoter by recruiting the CtBP/LSD1/CoREST complex, thus facilitating the EMT program and metastasis. CONCLUSIONS: Collectively, our findings indicate the critical role of m6A modification in GC and uncover METTL3/ZMYM1/E-cadherin signaling as a potential therapeutic target in anti-metastatic strategy against GC.

Asunto(s)

Adenosina/análogos & derivados , Transición Epitelial-Mesenquimal/genética , Metiltransferasas/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Adenosina/metabolismo , Animales , Biomarcadores de Tumor , Línea Celular Tumoral , Modelos Animales de Enfermedad , Proteína 1 Similar a ELAV/metabolismo , Perfilación de la Expresión Génica , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Masculino , Metiltransferasas/metabolismo , Ratones , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , Unión Proteica , ARN Mensajero/genética , ARN Mensajero/metabolismo , Transducción de Señal , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Transcriptoma

RESUMEN

Background: Robot-assisted surgical techniques have been introduced in recent years as an alternative minimally invasive approach for colorectal surgery. In practice, we found that the monopolar electrosurgical scissors had its unique advantages in preservation of the pelvic autonomic nerves. We performed a retrospective review of short-term results between using monopolar electrosurgical scissors and harmonic scalpel in robotic anterior resection (using the da Vinci® Surgical System) in rectal cancer patients. Method: Forty-six patients who underwent robotic anterior resection of rectal cancer from June 2016 to January 2018 were retrospectively analyzed and compared. Twenty-two cases underwent resection using monopolar electrosurgical scissors and 24 cases underwent resection using the harmonic scalpel. Patient characteristics, perioperative clinical results, complications, and pathological results were compared between two groups. Results: There were not significantly different patient characteristics between the two groups. The mean operative time was lesser in the monopolar electrosurgical scissors group than in the inharmonic scalpel group [95.59 ± 21.44 minutes versus 81.45 ± 13.89 minutes, P < .01]. The mean estimated blood loss was lesser in the monopolar electrosurgical scissors group than in the inharmonic scalpel group [48.64 ± 19.35 mL versus 61.82 ± 24.23 mL, P = .03]. The complication rate was 18.2% in the monopolar electrosurgical scissors group and 16.7% in the harmonic scalpel group (P = .89). The mean time of postoperational urinary catheter was lesser in the monopolar electrosurgical scissors group [3.73 ± 1.16 days versus 4.59 ± 1.71 days, P = .02]. The day to first passing flatus [3.45 ± 0.80 days versus 3.59 ± 1.14 days, P = .67], feeding time [4.50 ± 1.00 days versus 4.05 ± 1.87 days, P = .35], hospital stay [8.18 ± 3.74 days versus 8.68 ± 3.44 days, P = .52], and the mean number of harvested lymph nodes of detection [13.59 ± 1.71 versus 13.77 ± 1.41, P = .67] were comparable between procedures. Conclusion: Monopolar electrosurgical scissors were used safely and effectively in robotic anterior resection of rectal cancer (using the da Vinci Surgical System). The use of monopolar electrosurgical scissors has benefits in performing blunt and sharp separation in narrow pelvic and cheaper hospitalization expenses.

Asunto(s)

Electrocirugia/instrumentación , Ganglios Linfáticos/cirugía , Neoplasias del Recto/cirugía , Procedimientos Quirúrgicos Robotizados/instrumentación , Anciano , Pérdida de Sangre Quirúrgica , Ingestión de Alimentos , Femenino , Tracto Gastrointestinal/fisiopatología , Humanos , Tiempo de Internación , Escisión del Ganglio Linfático , Masculino , Persona de Mediana Edad , Tempo Operativo , Periodo Posoperatorio , Recuperación de la Función , Estudios Retrospectivos , Procedimientos Quirúrgicos Robotizados/efectos adversos , Instrumentos Quirúrgicos , Factores de Tiempo , Cateterismo Urinario

RESUMEN

We previously demonstrated that long non-coding RNA cytoskeleton regulator RNA (CYTOR), also known as Linc00152, was significantly overexpressed in colon cancer and conferred resistance to oxaliplatin-induced apoptosis. At the same time, elevated CYTOR expression was also reported in gastric cancer and exerted influences on epithelial-mesenchymal transition (EMT) markers. However, the precise mechanism by which CYTOR promotes the EMT phenotype and cancer metastasis remains poorly understood. Here, we showed that loss of epithelial characteristics and simultaneous gain of mesenchymal features correlated with CYTOR expression. Knockdown of CYTOR attenuated colon cancer cell migration and invasion. Conversely, ectopic expression of CYTOR induced an EMT program and enhanced metastatic properties of colon cancer cells. Mechanistically, the binding of CYTOR to cytoplasmic ß-catenin impeded casein kinase 1 (CK1)-induced ß-catenin phosphorylation that enabled it to accumulate and translocate to the nucleus. Reciprocally, ß-catenin/TCF complex enhanced the transcription activity of CYTOR in nucleus, thus forming a positive feed-forward circuit. Moreover, elevated CYTOR, alone or combined with overexpression of nuclear ß-catenin, was predictive of poor prognosis. Our findings suggest that CYTOR promotes colon cancer EMT and metastasis by interacting with ß-catenin, and the positive feed-forward circuit of CYTOR-ß-catenin might be a useful therapeutic target in antimetastatic strategy.

Asunto(s)

Neoplasias del Colon/genética , Neoplasias del Colon/metabolismo , Regulación Neoplásica de la Expresión Génica , ARN Largo no Codificante , Vía de Señalización Wnt , Animales , Línea Celular Tumoral , Neoplasias del Colon/mortalidad , Neoplasias del Colon/patología , Modelos Animales de Enfermedad , Transición Epitelial-Mesenquimal/genética , Técnica del Anticuerpo Fluorescente , Humanos , Inmunohistoquímica , Masculino , Ratones , Modelos Biológicos , Metástasis de la Neoplasia , Fosforilación , Pronóstico , Análisis de Supervivencia , Ensayos Antitumor por Modelo de Xenoinjerto , beta Catenina/metabolismo

RESUMEN

In recent years, accumulating evidence indicates that long noncoding RNAs (lncRNAs) have emerged as powerful influence factors in the progression of multiple malignancies. Dysregulation of lncRNA HNF1A-antisense 1 (HNF1A-AS1) has been reported in many types of human cancers, and studies on HNF1A-AS1 function in cancers revealed that HNF1A-AS1could act as either oncogene or tumor suppressor. Nevertheless, the functional involvement of HNF1A-AS1 in colon cancer remains unknown. In this study, we reported that HNF1A-AS1 was frequently upregulated in colon cancer tissues and associated with poor prognosis. Upregulated HNF1A-AS1 promoted colon cancer cell viability, migration and invasion both in vitro and in vivo. HNF1A-AS1 silencing impaired tumor growth and metastasis in xenograft model assay. Moreover, HNF1A-AS1 functioned as an oncogene in metastasis of colon cancer in part through serving as a competing endogenous RNA to modulate miRNA-34a expression, subsequently with repression of miR-34a/SIRT1/p53 feedback loop and activation of canonical Wnt signaling pathway. Our results demonstrated that HNF1A-AS1 mediated the metastatic progression of colon cancer in part through miR-34a/p53 signaling axis, and established its candidacy as a new prognostic biomarker and a potential novel therapeutic target.

Asunto(s)

Movimiento Celular , Neoplasias del Colon/genética , MicroARNs/genética , ARN Largo no Codificante/genética , Sirtuina 1/genética , Proteína p53 Supresora de Tumor/genética , Anciano , Animales , Unión Competitiva , Células CACO-2 , Proliferación Celular , Neoplasias del Colon/metabolismo , Neoplasias del Colon/patología , Retroalimentación Fisiológica , Femenino , Regulación Neoplásica de la Expresión Génica , Células HCT116 , Humanos , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , MicroARNs/metabolismo , Persona de Mediana Edad , Metástasis de la Neoplasia , Fenotipo , Unión Proteica , ARN Largo no Codificante/metabolismo , Transducción de Señal , Sirtuina 1/metabolismo , Factores de Tiempo , Carga Tumoral , Proteína p53 Supresora de Tumor/metabolismo , Regulación hacia Arriba

RESUMEN

BACKGROUND AND AIM: Long non-coding RNA zinc finger antisense 1 (ZFAS1) is frequently amplified in hepatocellular carcinoma and promotes metastasis by increasing zinc finger E-box binding homeobox 1 (ZEB1), which can potentiate the progression of epithelial-to-mesenchymal transition (EMT). However, the expression pattern and role of ZFAS1 in colonic cancer remains unknown. The present study aimed to investigate the role of ZFAS1 and its clinical significance in colonic cancer. METHODS: Paired clinical colonic cancer tissue samples and clinicopathologic characteristics of 73 patients were analyzed. Quantitative real-time polymerase chain reaction analysis was used to evaluate expression levels of ZFAS1 in colonic cancer tissues, cell lines, and plasma. ZEB1 and EMT-related markers expression levels also were explored. Cell biology assays were used to explore the biologic consequences of ZFAS1 in regulating cell proliferation and invasion, as well as the roles in regulating EMT. RESULTS: Zinc finger antisense 1 was up-regulated in colonic cancer tissues compared with adjacent mucosa (P < 0.01), and its expression level was significantly correlated with TNM stage, vascular invasion, and lymph node metastasis (P < 0.05). ZFAS1 and ZEB1 were also increased in patients' plasma. Moreover, ZFAS1 promoted proliferation, invasion, and impeded apoptosis. Knockdown of ZFAS1 decreased expression of ZEB1 and increased the epithelial markers E-cadherin, ZO-1 while decreasing mesenchymal markers vimentin and N-cadherin. CONCLUSIONS: Long non-coding RNA ZFAS1 may function as an oncogene by modulating ZEB1 to induce EMT. Manipulation of ZFAS1 level may be a novel approach to suppress colonic cancer progression. In addition, ZFAS1 in plasma has the potential to be a diagnostic biomarker of colonic cancer.

Asunto(s)

Neoplasias del Colon/genética , Neoplasias del Colon/patología , Expresión Génica/genética , ARN Largo no Codificante/fisiología , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/genética , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/metabolismo , Biomarcadores/sangre , Cadherinas/metabolismo , Línea Celular Tumoral , Proliferación Celular/genética , Neoplasias del Colon/diagnóstico , Progresión de la Enfermedad , Transición Epitelial-Mesenquimal , Humanos , Metástasis Linfática , Invasividad Neoplásica/genética , Estadificación de Neoplasias , Reacción en Cadena en Tiempo Real de la Polimerasa , Regulación hacia Arriba , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/sangre , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/fisiología

RESUMEN

Long noncoding RNAs act as crucial regulators in plenty of human cancers, yet their potential roles and molecular mechanisms in chemoresistance are poorly understood. This study showed that a novel lncRNA, long intergenic noncoding RNA 152 (Linc00152 ), promoted tumor progression and conferred resistance to oxaliplatin (L-OHP)-induced apoptosis in vitro and in vivo. It antagonized chemosensitivity through acting as a competing endogenous RNA to modulate the expression of miR-193a-3p, and then erb-b2 receptor tyrosine kinase 4 (ERBB4). Knockdown of ERBB4 in colon cancer cells decreased AKT phosphorylation, which resulted in decreased L-OHP resistance. Consistent with above findings, the specific AKT signaling inhibitor and activator were used, respectively, which demonstrated that Linc00152 contributed to L-OHP resistance at least partly through activating AKT pathway. Further studies indicated that Linc00152 was increased and appeared to be an independent prognostic factor for decreased survival and increased disease recurrence in stage II and III colon cancer patients undergoing L-OHP-based chemotherapy after surgery. Collectively, our findings established Linc00152 as a candidate prognostic indicator of outcome and drug responsiveness in colon cancer patients, and the involvement of competing endogenous RNAs mechanism in Linc00152/miR-193a-3p/ERBB4/AKT signaling axis may provide a novel choice in the investigation of drug resistance.

Asunto(s)

Neoplasias del Colon/patología , Resistencia a Antineoplásicos , Compuestos Organoplatinos/farmacología , ARN Largo no Codificante/genética , Animales , Células CACO-2 , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Neoplasias del Colon/genética , Regulación Neoplásica de la Expresión Génica , Células HT29 , Humanos , Ratones , Trasplante de Neoplasias , Oxaliplatino , Pronóstico , Transducción de Señal/efectos de los fármacos , Regulación hacia Arriba

RESUMEN

BACKGROUND: Tumor metastasis is one of the leading causes of poor prognosis for colorectal cancer (CRC) patients. Loss of Smad4 contributes to aggression process in many human cancers. However, the underlying precise mechanism of aberrant Smad4 expression in CRC development is still little known. RESULTS: miR-20a-5p negatively regulated Smad4 by directly targeting its 3'UTR in human colorectal cancer cells. miR-20a-5p not only promoted CRC cells aggression capacity in vitro and liver metastasis in vivo, but also promoted the epithelial-to-mesenchymal transition process by downregulating Smad4 expression. In addition, tissue microarray analysis obtained from 544 CRC patients' clinical characters showed that miR-20a-5p was upregulated in human CRC tissues, especially in the tissues with metastasis. High level of miR-20a-5p predicted poor prognosis in CRC patients. METHODS: Five miRNA target prediction programs were applied to identify potential miRNA(s) that target(s) Smad4 in CRC. Luciferase reporter assay and transfection technique were used to validate the correlation between miR-20a-5p and Smad4 in CRC. Wound healing, transwell and tumorigenesis assays were used to explore the function of miR-20a-5p and Smad4 in CRC progression in vitro and in vivo. The association between miR-20a-5p expression and the prognosis of CRC patients was evaluated by Kaplan-Meier analysis and multivariate cox proportional hazard analyses based on tissue microarray data. CONCLUSIONS: miR-20a-5p, as an onco-miRNA, promoted the invasion and metastasis ability by suppressing Smad4 expression in CRC cells, and high miR-20a-5p predicted poor prognosis for CRC patients, providing a novel and promising therapeutic target in human colorectal cancer.

Asunto(s)

Neoplasias Colorrectales/patología , MicroARNs/fisiología , Proteína Smad4/genética , Regiones no Traducidas 3' , Adulto , Anciano , Animales , Línea Celular Tumoral , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/mortalidad , Regulación hacia Abajo , Transición Epitelial-Mesenquimal , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Persona de Mediana Edad , Invasividad Neoplásica , Metástasis de la Neoplasia , Modelos de Riesgos Proporcionales , Proteína Smad4/antagonistas & inhibidores

RESUMEN

Conventional high-recurrence risk factors are not sufficient to predict post-operative risk of tumor recurrence or sensitivity to 5-fluorouracil (5-FU)-based chemotherapy for stage II colon cancer. DDA1, an evolutionarily conserved gene located at 19p13.11, may be involved in the activation of nuclear factor kappaB (NFκB). This study aimed to investigate whether DDA1 contributes to tumorigenesis and progression of stage II colon cancer via activation of the NFκB pathway. We found that positive expression of DDA1 alone or in combination with p65 nuclear translocation correlated with increased risk of tumor recurrence in patients with stage IIB-IIC colon cancer. DDA1 overexpression in colon cancer lines promoted cell proliferation, facilitated cell cycle progression, inhibited 5-FU-induced apoptosis, enhanced invasion, and induced the epithelial-mesenchymal transition. Suppression of DDA1 inhibited tumor progression, and reduced tumor growth in vivo. We also demonstrated that DDA1-mediated tumor progression is associated with the activation of the NFκB/COP9 signalosome 2(CSN2)/glycogen synthase kinase3ß (GSK3ß) pathway. These results indicate that DDA1 promotes colon cancer progression through activation of NFκB/CSN2/GSK3ß signaling. DDA1, together with NFκB activation status, may serve as a sensitive biomarker for tumor recurrence risk and prognosis in patients with stage IIB-IIC colon cancers.

Asunto(s)

Neoplasias del Colon/metabolismo , Proteínas de Unión al ADN/metabolismo , Anciano , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Western Blotting , Complejo del Señalosoma COP9/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Proliferación Celular/genética , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/genética , Proteínas de Unión al ADN/genética , Progresión de la Enfermedad , Femenino , Fluorouracilo/administración & dosificación , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Células HCT116 , Células HT29 , Humanos , Masculino , Ratones Desnudos , Persona de Mediana Edad , FN-kappa B/metabolismo , Estadificación de Neoplasias , Periodo Posoperatorio , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genética , Trasplante Heterólogo

RESUMEN

BACKGROUND: Long non-coding RNA-activated by TGF-ß (lncRNA-ATB) promotes the invasion-metastasis cascade in hepatocellular carcinoma via downregulating E-cadherin (E-cad) and inducing epithelial-to- mesenchymal transition (EMT) and is clinically significant in human colon cancer. However, its molecular mechanisms in colon cancer progression remain unclear. This study aimed to elucidate the role of lncRNA-ATB and its clinical value in colon cancer. METHODS: Expression levels of lncRNA-ATB in colon cancer tissues and colon cancer cell lines were evaluated using quantitative real-time polymerase chain reaction. The clinicopathological significance and prognostic value of lncRNA-ATB were investigated, and roles of lncRNA-ATB in regulating E-cad and other EMT-related markers expression and colon cancer progression were evaluated in vitro. Expression levels of lncRNA-ATB and E-cad in human plasma were evaluated. RESULTS: Long non-coding RNA-activated by TGF-ß was upregulated in colon cancer tissues compared with adjacent mucosa (P < 0.001). LncRNA-ATB levels were also higher in metastatic cancer tissues (P < 0.001). Among the three highly invasive colon cancer cell lines, lncRNA-ATB levels were relatively higher with concurrent low levels of E-cad compared with levels in the three low-invasive cell lines. LncRNA-ATB expression correlated with pN stage (P < 0.01) and American Joint Committee on Cancer stage (P < 0.01). Striking differences were observed in overall survival and disease-free survival in cases with both high lncRNA-ATB expression and low E-cad expression. Reduction of lncRNA-ATB increased expression of epithelial markers E-cad, ZO-1, and decreased expression of mesenchymal markers ZEB1 and N-cadherin (N-cad), and significantly influenced colon cancer cell progression. Plasma lncRNA-ATB was upregulated in colon cancer patients one month after surgery (P < 0.05). CONCLUSIONS: Long non-coding RNA-activated by TGF-ß may act on colon tumorigenesis by suppressing E-cad expression and promoting EMT process, and lncRNA-ATB inhibition may provide a promising therapeutic option for suppressing colon cancer progression.

Asunto(s)

Cadherinas/genética , Cadherinas/metabolismo , Carcinogénesis/genética , Neoplasias del Colon/genética , Neoplasias del Colon/patología , Expresión Génica/genética , ARN Largo no Codificante/fisiología , Factor de Crecimiento Transformador beta/fisiología , Neoplasias del Colon/mortalidad , Neoplasias del Colon/terapia , Progresión de la Enfermedad , Regulación hacia Abajo , Femenino , Humanos , Masculino , Terapia Molecular Dirigida , Invasividad Neoplásica , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , ARN Largo no Codificante/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Tasa de Supervivencia , Factor de Crecimiento Transformador beta/metabolismo , Regulación hacia Arriba

RESUMEN

The THO complex 1 (Thoc1) is a nuclear matrix protein playing vital roles in transcription elongation and mRNA export. Recently, aberrant expression of Thoc1 has been reported in an increasing array of tumor types. However, the clinical significance of Thoc1 expression in colorectal cancer (CRC) is still unknown. The present study aimed to characterize the expression of Thoc1 in human CRC and evaluate its clinical significance. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting analyses showed that the mRNA and protein expression of Thoc1 in CRC specimens was significantly higher than that in adjacent normal colon mucosae. Immunohistochemistry (IHC) was conducted to characterize the expression pattern of Thoc1 in 185 archived paraffin-embedded CRC specimens. Statistical analyses revealed that high levels of Thoc1 expression were associated with the clinical stages and tumor differentiation. CRC patients with high levels of Thoc1 expression had poorer overall-survival and disease-free survival, whereas those with lower levels of Thoc1 expression survived longer. Furthermore, multivariate Cox regression analyses demonstrated that Thoc1 expression remained an independent prognostic factor for increased disease recurrence and decreased survival. Our results suggest for the first time that Thoc1 is involved in the development and progression of CRC, and elevated expression of Thoc1 is associated with aggressive phenotype and poor prognosis in CRC. These findings may prove to be clinically useful for developing a new therapeutic target of CRC treatment.

Asunto(s)

Proteínas de Ciclo Celular/genética , Colon/patología , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/genética , Proteínas Nucleares/genética , Recto/patología , Regulación hacia Arriba , Anciano , Proteínas de Ciclo Celular/análisis , Colon/metabolismo , Neoplasias Colorrectales/patología , Proteínas de Unión al ADN , Supervivencia sin Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Proteínas Nucleares/análisis , Pronóstico , Proteínas de Unión al ARN , Recto/metabolismo

RESUMEN

Novel long non-coding RNA Fer-1-like protein 4 (FER1L4) has been confirmed to play crucial regulatory roles in tumor progression. It exerts an impact on tumor suppression and functions as a competing endogenous RNA (ceRNA) by sponging miR-106a-5p in gastric cancer. However, its clinical significance in colon cancer is completely unknown. The aim of the present study was to annotate the role of FER1L4 and its clinical value in colon cancer. The results showed the aberrant expression of FER1L4 and miR-106a-5p in colon cancer tissues. In addition, significant negative correlation between FER1L4 and miR-106a-5p expression levels was observed. Among the colon cancer cell lines, FER1L4 levels were relatively lower, with concurrent high levels of miR-106a-5p. Restoration of FER1L4 decreased the expression of miR-106a-5p, and had a significant influence on colon cancer cell proliferation, migration and invasion. The FER1L4 expression was correlated with depth of tumor invasion, lymph node metastasis, vascular invasion and clinical stage. Moreover, striking differences in overall survival and disease-free survival were observed for the cases with both low FER1L4 expression and high miR-106a-5p expression compared with cases with high FER1L4 expression and low miR-106a-5p expression. Circulating FER1L4 and miR-106a-5p levels were decreased and increased, respectively, in colon cancer patients after surgery. Our findings indicated that FER1L4 could exert a tumor suppressive impact on colon cancer, which at least, in part, through suppressing miR-106a-5p expression, and depletion of FER1L4, alone or combined with overexpression of miR-106a-5p, is predictive of poor prognosis in colon cancer and may play a crucial role in cancer prevention and treatment.

Asunto(s)

Transformación Celular Neoplásica/patología , Neoplasias del Colon/patología , MicroARNs/metabolismo , ARN Largo no Codificante/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Transformación Celular Neoplásica/genética , Neoplasias del Colon/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Células HCT116 , Humanos , Metástasis Linfática , Masculino , MicroARNs/sangre , MicroARNs/genética , Persona de Mediana Edad , Invasividad Neoplásica/genética , Invasividad Neoplásica/patología , ARN Largo no Codificante/sangre , ARN Largo no Codificante/genética

RESUMEN

A large amount of soil loss is caused by a small number of extreme events that are mainly responsible for the time compression of geomorphic processes. The aim of this study was to analyze suspended sediment transport during extreme erosion events in a mountainous watershed. Field measurements were conducted in Wangjiaqiao, a small agricultural watershed (16.7 km(2)) in the Three Gorges Area (TGA) of China. Continuous records were used to analyze suspended sediment transport regimes and assess the sediment loads of 205 rainfall-runoff events during a period of 16 hydrological years (1989-2004). Extreme events were defined as the largest events, ranked in order of their absolute magnitude (representing the 95(th) percentile). Ten extreme erosion events from 205 erosion events, representing 83.8% of the total suspended sediment load, were selected for study. The results of canonical discriminant analysis indicated that extreme erosion events are characterized by high maximum flood-suspended sediment concentrations, high runoff coefficients, and high flood peak discharge, which could possibly be explained by the transport of deposited sediment within the stream bed during previous events or bank collapses.

Asunto(s)

Ecosistema , Suelo , Agua , China , Análisis Discriminante , Inundaciones , Geografía , Sedimentos Geológicos , Lluvia

RESUMEN

Erosion and sediment characteristics were measured using simulated rainfall on two cultivated soils from the Loess Plateau, China. The size distribution of eroded sediment (non-dispersed) was compared with equivalent measurements of the same samples after chemical and mechanical dispersion(dispersed) to investigate the aggregation ratio (AR) and enrichment ratio (ER). Results show that clay content is increasing with the length and rainfall intensity. The loessial soil increased by 8.77% and 2.43%, but the Lou soil increased by only 2.76% and 0.4%. With the increase of slope, the clay content of the two loess reduced by 4.91% and 3.93%, respectively. AR values were less than 1 and ER values were greater than 1. These indicated that relatively slight clay dispersion occurred and that most of the clay in the sediments was in the form of aggregates. The results will improve understanding of erosion and sedimentation processes, which in turn will improve erosion modeling. Knowledge of temporal variations of clay in sediment can also provide the basis for understanding and modeling the transfer of nutrients on hillslope.

Asunto(s)

Silicatos de Aluminio/análisis , Conservación de los Recursos Naturales , Lluvia , Suelo/análisis , Movimientos del Agua , China , Arcilla , Simulación por Computador , Conservación de los Recursos Naturales/métodos , Tamaño de la Partícula , Análisis Espacio-Temporal

RESUMEN

OBJECTIVES: (1) To investigate the levels of the serum soluble endothelial growth factor receptor-1 in women with preeclampsia and compare the difference between the groups of the mild preeclampsia, severe preeclampsia and eclampsia. For more, to analyze the relativity between the levels of the serum soluble vascular growth factor receptor-1 and preeclampsia. (2) To detect the expression of the membrane-bound VEGFR-1 protein in the placenta tissue of the women with preeclampsia and compare the difference between the groups of the mild preeclampsia, severe preeclampsia and eclampsia, Then to analyze the relativity between the expression of the membrane-bound endothelial growth factor receptor-1 and preeclampsia. METHODS: (1) The serum levels of sVEGFR-1 in 10 women with mild preeclampsia, 10 women with severe preeclampsia, 10 women with eclampsia, 10 women without preeclampsia were detected by the quantitative sandwich enzyme immunoassay technique. (2) Immunohistochemistry and quantitative analysis were used to detect membrane-bound VEGFR-1 contents and distribution in the placenta tissue. RESULTS: (1) The results showed that the serum sVEGFR-1 levels of all preeclampsia groups were relatively higher than those of control group (P < 0.05) and that there were significant differences between the groups of the mild preeclampsia, severe preeclampsia and eclampsia. (2) In placentas, the positive staining was detected predominantly in the membranes of villus syncytiotrophoblast cells, extravillous trophoblast cells, and villus endothelial cells. In fetal membranes, the positive staining was detected predominantly in amnionic endothelial cells. (3) The contents of membrane-bound VEGFR-1 in placenta of preeclampsia groups were relatively lower than that of control group. There were significant differences between membrane-bound VEGFR-1 contents of the mild preeclampsia,severe preeclampsia and eclampsia (P < 0.05). (4) The ratio of the sVEGFR-1 concentration in serum and the membrane-bound VEGFR-1 contents in placenta of preeclampsia groups (sVEGFR-1/ membrane-bound VEGFR-1) was relatively higher than that of control group (P < 0.05) and there were significant differences between the groups of the mild preeclampsia, severe preeclampsia and eclampsia (P < 0.05). CONCLUSIONS: (1) The serum sVEGFR-1 levels of preeclampsia groups were relatively higher than those of control group, the VEGFR-1 may be related to preeclampsia. (2) The contents of membrane-bound VEGFR-1 in placenta of preeclampsia groups were relatively lower than that of control group, the membrane-bound VEGFR-1 may relate to preeclampsia. (3) The ratio of the sVEGFR-1 concentration in serum and the membrane-bound VEGFR-1 contents in placenta of preeclampsia groups (sVEGFR-1/membrane-bound VEGFR-1) was relatively higher than that of control group, the preeclampsia may contribute to VEGFR-1/ PLGF and sVEGFR-1/membrane-bound.

Asunto(s)

Preeclampsia/metabolismo , Receptor 1 de Factores de Crecimiento Endotelial Vascular/metabolismo , Adulto , Femenino , Humanos , Placenta/metabolismo , Embarazo , Receptor 1 de Factores de Crecimiento Endotelial Vascular/sangre