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1.
Heliyon ; 10(7): e29285, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38633650

RESUMEN

Background: EEPD1 is vital in homologous recombination, while its role in cancer remains unclear. Methods: We performed multiple pan-cancer analyses of EEPD1 with bioinformatics methods, such as gene expression, gene alterations, Prognosis and enrichment analysis, tumor microenvironment, immune cell infiltration, TMB, MSI, immunotherapy, co-expression of genes, and drug resistance. Finally, RT-qPCR, EdU, and transwell assays helped investigate the impact of EEPD1 on CRC cells. Results: EEPD1 was dysregulated and correlated with bad prognosis in several cancers. GSVA and GSEA revealed that EEPD1 was primarily associated with the "WNT_BETA_CATENIN_SIGNALING," "ribonucleoprotein complex biogenesis," "Ribosome," and "rRNA processing." The infiltration of CD8+ T cells, MAIT cells, iTreg cells, NK cells, Tc cells, Tex cells, Tfh cells, and Th1 cells were negatively correlated with EEPD1 expression. Additionally, EEPD1 is significantly associated with TMB and MSI in COAD, while enhanced CRC cell proliferation and migration. Conclusions: EEPD1 was dysregulated in human cancers and correlated with various cancer patient prognoses. The dysregulated EEPD1 expression can affect tumor-infiltrating immune cells and immunotherapy response. Therefore, EEPD1 could act as an oncogene associated with immune cell infiltration in CRC.

2.
Cancer Gene Ther ; 30(6): 905-916, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36890211

RESUMEN

Hypoxia-mediated tumor progression is a major clinical challenge in human cancers including colorectal cancer (CRC). In addition, exosome-mediated transfer of miRNAs from cancer-associated fibroblasts (CAFs) to cancer cells could promote tumor progression. However, the mechanisms by which hypoxia CAFs promotes CRC progression remain largely unknown. CAFs and normal fibroblasts (NFs) were isolated from CRC tissues and adjacent normal tissues. Next, exosomes were isolated from the supernatant of CAFs that cultured under normoxia (CAFs-N-Exo) and hypoxia (CAFs-H-Exo). RNA-sequencing was then performed to identify differentially expressed miRNAs (DEMs) between CAFs-N-Exo and CAFs-H-Exo. Compared with exosomes derived from normoxia CAFs, exosomes derived from hypoxic CAFs were able to promote CRC cell proliferation, migration, invasion, stemness and reduce the sensitivity of CRC cells to 5-fluorouracil (5-FU). In addition, miR-200b-3p levels were dramatically decreased in exosomes derived from hypoxic CAFs. Remarkably, increasing exosomal miR-200b-3p in hypoxic CAFs reversed the promoting effects of hypoxic CAFs on CRC cell growth in vitro and in vivo. Furthermore, miR-200b-3p agomir could inhibit CRC cell migration, invasion, stemness and increase the sensitivity of SW480 cells to 5-FU via downregulating ZEB1 and E2F3. Collectively, loss of exosomal miR-200b-3p in hypoxia CAFs could contribute to CRC progression via upregulation of ZEB1 and E2F3. Thus, increasing exosomal miR-200b-3p might serve as an alternative approach for the treatment of CRC.


Asunto(s)
Fibroblastos Asociados al Cáncer , Neoplasias Colorrectales , Exosomas , MicroARNs , Humanos , Fibroblastos Asociados al Cáncer/patología , Regulación hacia Arriba , MicroARNs/genética , Transformación Celular Neoplásica/genética , Carcinogénesis/genética , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Fluorouracilo/farmacología , Exosomas/genética , Exosomas/patología , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Línea Celular Tumoral , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/genética , Factor de Transcripción E2F3
3.
Front Oncol ; 12: 920131, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36276139

RESUMEN

Hypoxia-mediated tumor progression is a major problem in colorectal cancer (CRC). MicroRNA (miR)-200b-3p can attenuate tumorigenesis in CRC, while exosomal miRNAs derived from cancer-associated fibroblasts (CAFs) can promote cancer progression. Nevertheless, the function of exosomal miR-200b-3p derived from CAFs in CRC remains unclear. In this study, CAFs and normal fibroblasts (NFs) were isolated from CRC and adjacent normal tissues. Next, exosomes were isolated from the supernatants of CAFs cultured under normoxia and hypoxia. Cell viability was tested using the cell counting kit-8 assay, and flow cytometry was used to assess cell apoptosis. Cell invasion and migration were evaluated using the transwell assay. Dual-luciferase was used to investigate the relationship between miR-200b-3p and high-mobility group box 3 (HMBG3). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to determine the miR-200b-3p and HMBG3 level. Our results found that the miR-200b-3p level was sharply reduced in CRC tissues compared to adjacent normal tissues. Additionally, the miR-200b-3p level was reduced in exosomes derived from hypoxic CAFs compared to exosomes derived from CAFs under normoxia. Exosomes derived from hypoxic CAFs weakened the sensitivity of CRC cells to 5-fluorouracil (5-FU) compared to hypoxic CAFs-derived exosomes. However, hypoxic CAFs-derived exosomes with upregulated miR-200b-3p increased the sensitivity of CRC cells to 5-fluorouracil (5-FU) compared to hypoxic CAFs-derived exosomes. In addition, HMBG3 was identified as the downstream target of miR-200b-3p in CRC cells, and its overexpression partially reversed the anti-tumor effect of the miR-200b-3p agomir on CRC via the mediation of the ß-catenin/c-Myc axis. Furthermore, compared to exosomes derived from normoxia CAFs, exosomes derived from hypoxic CAFs weakened the therapeutic effects of 5-FU on CRC in vivo via the upregulation of HMGB3 levels. Collectively, the loss of exosomal miR-200b-3p in hypoxia CAFs reduced the sensitivity to 5-FU in CRC by targeting HMGB3. Thus, our research outlines a novel method for the treatment of CRC.

4.
Front Cell Dev Biol ; 10: 891482, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35712661

RESUMEN

Colorectal cancer is one of the common malignant tumors in the digestive system, with high incidence and mortality rate. Therefore, there is an urgent need to identify and develop new molecular targets for colorectal cancer treatment. Previous studies have pointed out the important role of HMGB3 in tumors, and how it works in colorectal cancer needs to be studied in depth. In this study, we found that HMGB3 was highly expressed in COAD in the cBioPortal and GEPIA2 databases. Kaplan-Meier analysis showed that compared with patients with lower HMGB3 levels, patients with higher HMGB3 levels had poorer OS (p = 0.001). We also found a correlation between HMGB3 expression and immune infiltration of CRC. To investigate the mechanism of HMGB3 knockdown-mediated colorectal cancer inhibition, we detected a downregulation of N-cadherin, Vimentin and ß-catenin proteins after knockdown of HMGB3. Taken together, HMGB3 can be an effective target for CRC treatment in the future, and we have reason to believe that HMGB3 will be of greater value in more tumors in the near future.

5.
Int J Colorectal Dis ; 37(4): 757-767, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35303158

RESUMEN

PURPOSE: This study examined the short- and long-term outcomes of laparoscopic and open splenic flexure colon cancer (SFCC) surgery. METHOD: Systematic literature searches were performed in PubMed and Ovid to compare laparoscopic and open colectomy for SFCC. The last search was conducted on November 7, 2021. Surgical and survival outcomes were collected and analyzed. This meta-analysis was performed using Review Manager Software (v 5.3). RESULTS: This study included seven publications with 2397 patients published between 2011 and 2021. A significant difference in operative time was seen in the laparoscopic group (P = 0.01, WMD = 50.13, 95%CI [10.32, 89.94], I2 = 97%); loss of blood estimated (P < 0.001, WMD = -101.88, 95%CI [-161.65, -42.11], I2 = 82%) and the incidence of overall complications (P < 0.001, OR = 0.53, 95%CI [0.38, 0.75], I2 = 0%) of laparoscopic procedure were greatly decreased. There were similar results as compared in the two groups in terms of lymph node harvesting (P = 0.71, WMD = 0.49, 95%CI [-2.13, 3.12], I2 = 93%) and the distance of proximal (P = 0.50, WMD = -1.09, 95%CI [-4.26, 2.08], I2 = 96%) or distal (P = 0.18, WMD = 2.44, 95%CI [-1.13, 6.01], I2 = 97%) resection margin. In addition, no significant differences were observed on overall/disease-free survival over 3/5 years between the two procedures. An analysis of subgroups that used propensity matching scores produced similar results. CONCLUSION: The laparoscopic procedure is clinically safe and feasible for SFCC. It shows the advantages in decreasing intraoperative blood loss and overall complications, and the long-term survival outcomes would not be affected. Randomized clinical trials with a larger sample size are warranted in the future for further investigation.


Asunto(s)
Colon Transverso , Neoplasias del Colon , Laparoscopía , Colectomía/efectos adversos , Colectomía/métodos , Colon Transverso/cirugía , Neoplasias del Colon/cirugía , Humanos , Laparoscopía/efectos adversos , Laparoscopía/métodos , Tempo Operativo , Complicaciones Posoperatorias/epidemiología , Resultado del Tratamiento
6.
J Laparoendosc Adv Surg Tech A ; 31(6): 621-626, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32833585

RESUMEN

Background: This study aimed to compare polypectomy during both insertion and withdrawal phase versus during withdrawal phase only. Method: We performed literature searching in PubMed and Ovid for randomized clinical trials (RCTs) that compared polypectomy during both insertion and withdrawal phase versus during withdrawal phase only on April 3, 2020. The primary outcome was adenoma detection rate (ADR). Results: Five RCTs published between 2012 and 2020 with a total of 2694 individuals were included in this meta-analysis. No significant difference was observed between the two groups for ADR (P = .99, odds ratio = 1.00, 95% confidence interval [CI] 0.84-1.19, I2 = 0%), or average number of adenomas per individuals (P = .53, weighted mean difference [WMD] = 0.04, 95% CI -0.09 to 0.17, I2 = 30%). Besides, polypectomy during both insertion and withdrawal group showed significantly longer time for insertion phase (P = .01, WMD = 2.16, 95% CI 0.47-3.84, I2 = 95%), and shorter time for withdrawal phase (P = .010, WMD = -2.32, 95% CI -4.09 to -0.56, I2 = 94%), although the total procedure time was not significantly different between the two groups. Conclusion: No obvious advantages were observed for polypectomy during both insertion and withdrawal phase. We are looking forward to the long-term outcomes of these studies. More studies are warranted in the future for further exploration, especially the detection rate of small lesions.


Asunto(s)
Adenoma/diagnóstico por imagen , Adenoma/cirugía , Pólipos del Colon/cirugía , Colonoscopía/métodos , Neoplasias Colorrectales/diagnóstico por imagen , Neoplasias Colorrectales/cirugía , Adenoma/patología , Pólipos del Colon/diagnóstico por imagen , Humanos , Tempo Operativo , Ensayos Clínicos Controlados Aleatorios como Asunto
7.
Biosci Rep ; 40(3)2020 03 27.
Artículo en Inglés | MEDLINE | ID: mdl-32110802

RESUMEN

Heat shock factor 1 (HSF1) is a powerful multifaceted oncogenic modifier that plays a role in maintaining the protein balance of cancer cells under various stresses. In recent studies, there have been reports of increased expression of HSF1 in colorectal cancer (CRC) cells, and the depletion of the HSF1 gene knockdown has inhibited colon cancer growth both in vivo and in vitro. Therefore, HSF1 is a promising target for colon cancer treatment and chemoprevention. In the present study, we found that Schizandrin A (Sch A) significantly inhibited the growth of CRC cell lines by inducing cell cycle arrest, apoptosis and death. Through HSE luciferase reporter assay and quantitative PCR (qPCR), we identified Sch A as a novel HSF1 inhibitor. In addition, Sch A could effectively inhibit the induction of HSF1 target proteins such as heat-shock protein (HSP) 70 (HSP70) and HSP27, whether in heat shock or normal temperature culture. In the Surface Plasmon Resonance (SPR) experiment, Sch A showed moderate affinity with HSF1, further confirming that Sch A might be a direct HSF1 inhibitor. The molecular docking and molecular dynamic simulation results of HSF1/Sch A suggested that Sch A formed key hydrogen bond and hydrophobic interactions with HSF1, which may contribute to its potent HSF1 inhibition. These findings provide clues for the design of novel HSF1 inhibitors and drug candidates for colon cancer treatment.


Asunto(s)
Neoplasias Colorrectales/tratamiento farmacológico , Ciclooctanos/farmacología , Factores de Transcripción del Choque Térmico/metabolismo , Lignanos/farmacología , Compuestos Policíclicos/farmacología , Apoptosis/efectos de los fármacos , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , China , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/genética , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Ciclooctanos/metabolismo , Proteínas de Unión al ADN/genética , Proteínas de Choque Térmico HSP27/genética , Proteínas HSP70 de Choque Térmico/genética , Factores de Transcripción del Choque Térmico/efectos de los fármacos , Factores de Transcripción del Choque Térmico/genética , Humanos , Lignanos/metabolismo , Simulación del Acoplamiento Molecular , Compuestos Policíclicos/metabolismo , Factores de Transcripción/genética
8.
Oncol Rep ; 42(1): 213-223, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31115559

RESUMEN

Colorectal cancer (CRC) is one of the most common types of malignancy worldwide. Distant metastasis is a key cause of CRC­associated mortality. MEIS2 has been identified to be dysregulated in several types of human cancer. However, the mechanisms underlying the regulatory role of MEIS2 in CRC metastasis remain largely unknown. For the first time, the present study demonstrated that MEIS2 serves a role as a promoter of metastasis in CRC. In vivo and in vitro experiments revealed that knockdown of MEIS2 significantly suppressed CRC migration, invasion and the epithelial­mesenchymal transition. Furthermore, microarray and bioinformatics analyses were performed to investigate the underlying mechanisms of MEIS2 in the regulation of CRC metastasis. Additionally, it was identified that a high expression of MEIS2 was significantly associated with a shorter overall survival time for patients with CRC. The present study demonstrated that MEIS2 may serve as a novel biomarker for CRC.


Asunto(s)
Neoplasias Colorrectales/patología , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Regulación hacia Arriba , Animales , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Transición Epitelial-Mesenquimal , Regulación Neoplásica de la Expresión Génica , Células HCT116 , Humanos , Ratones , Metástasis de la Neoplasia , Trasplante de Neoplasias , Análisis de Supervivencia
9.
Oncotarget ; 8(53): 91674-91683, 2017 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-29207676

RESUMEN

Circular RNAs (circRNAs) as a novel type of noncoding RNAs (ncRNAs) are widely studied in the development of human various diseases, including cancer. Here, we found circular RNA hsa_circ_000984 encoded by the CDK6 gene was remarkably upregulated in the tissues of colorectal cancer (CRC) patients and in the CRC cell lines. Moreover, high expression level of hsa_circ_000984 was significantly associated with advanced colorectal cancer. Further analysis revealed that hsa_circ_000984 knockdown could inhibit cell proliferation, migration, invasion in vitro and tumor formation in vivo in CRC cell lines. Mechanically, we found that hsa_circ_000984 may act as a competing endogenous RNA (ceRNA) by competitively binding miR-106b and effectively upregulate the expression of CDK6, thereby inducing a series of malignant phenotypes of tumor cells. Taken together, these observations suggest that the hsa_circ_000984 could mediate the expression of gene CDK6 by acting as a ceRNA, which may contribute to a better understanding of between the regulatory miRNA network and CRC pathogenesis.

10.
Oncotarget ; 8(28): 46565-46579, 2017 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-28430621

RESUMEN

The prognostic value of lymphovascular invasion (LVI) in stage I/II colorectal cancer (CRC) does not reach a consensus. To systematically assess prognostic significance of LVI, databases of PubMed, Web of Science, and Embase were searched from inception up to 10 Dec 2016. The pooled hazard ratio (HR) and 95% confidence intervals (CI) were used to determine the prognostic effects. Nineteen relevant studies including 9881 total patients were enrolled. Our results showed that LVI is significantly associated with poor prognosis in overall survival (OS) (HR=2.15, 95 % CI=1.72-2.68, P < 0.01) and disease-free survival (DFS) (HR=1.73, 95% CI=1.50-1.99, P < 0.01), which is similar in stage II patients. Further subgroup analysis revealed that the significance of the association between LVI and worse prognosis in CRC patients is not affected by below factors, including geographic setting, LVI positive rate, treatment, tumor site, and quality of the study. The current meta-analysis suggests that LVI may be a poor prognostic factor for stage I/II CRC patients.


Asunto(s)
Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Humanos , Invasividad Neoplásica , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , Sesgo de Publicación , Factores de Riesgo
11.
Tumour Biol ; 37(10): 13225-13235, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27456362

RESUMEN

Ubiquitin-proteasome system regulates cell proliferation, apoptosis, angiogenesis, and motility, which are processes with particular importance for carcinogenesis. UBA protein 2-like protein (UBAP2L) was found to be associated with proteasome; however, its biological function is largely unknown. In this study, the mRNA levels of UBAP2L in human normal and colorectal carcinoma tissues were analyzed using the datasets from the publicly available Oncomine database ( www.oncomine.org ) and found UBAP2L was overexpressed in colorectal carcinoma tissues. Furthermore, we elucidated the role of UBAP2L in human colorectal cancer via an RNA interference lentivirus system in three colorectal carcinoma cell lines HCT116, SW1116, and RKO. Knockdown of UBAP2L led to suppressed cell proliferation and impaired colony formation. UBAP2L depletion in HCT116 and RKO cells also induced cell cycle arrest as well as apoptosis. Moreover, the phosphorylation of PRAS40, Bad, and the cleavage of PARP were remarkably increased after UBAP2L knockdown by Intracellular signaling array and also the activation of P38 was obviously decreased and the cleavage of Caspase 3 and Bax were increased after UBAP2L silencing by western blot assay, indicated that UBAP2L might be involved in the cell growth by the regulation of apoptosis-related proteins. Our findings indicated that UBAP2L may be essential for colorectal carcinoma growth and survival. Lentivirus-mediated small interfering RNA against UBAP2L might serve as a potential therapeutic approach for the treatment of colorectal cancer.


Asunto(s)
Apoptosis , Neoplasias Colorrectales/metabolismo , Enzimas Activadoras de Ubiquitina/metabolismo , Apoptosis/genética , Biomarcadores , Ciclo Celular , Puntos de Control del Ciclo Celular/genética , Línea Celular Tumoral , Proliferación Celular , Neoplasias Colorrectales/genética , Biología Computacional/métodos , Bases de Datos de Ácidos Nucleicos , Expresión Génica , Perfilación de la Expresión Génica , Técnicas de Silenciamiento del Gen , Silenciador del Gen , Células HCT116 , Humanos , ARN Interferente Pequeño/genética , Enzimas Activadoras de Ubiquitina/genética
12.
World J Surg Oncol ; 13: 320, 2015 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-26596801

RESUMEN

BACKGROUND: The objective of this study was to investigate the safety and long-term clinical effect of intraperitoneal implantation of sustained-release 5-fluorouracil in patients with advanced colorectal cancer during radical resection. METHODS: A total of 202 patients with advanced colorectal cancer undergoing radical operations were randomly divided into an experimental group (98 cases, intraoperative intraperitoneal implantation of sustained-release 5-fluorouracil 600 mg as local chemotherapy) and a control group (104 cases, without local chemotherapy). The clinical data of the two groups was compared including toxicity, complications, local recurrence rate, distant metastasis, disease-free survival, and 1-, 3-, and 5-year survival rates. RESULTS: Both groups of patients were followed up for more than 5 years, the longest follow-up time was 7.5 years. Bone marrow suppression, hepato-renal function, postoperative anastomotic leakage, pelvic effusion, incision infection, the incidence of intestinal obstruction, venting time, and hospital stay after operation (days) between two groups had no statistical significant difference. Locoregional recurrence and liver metastasis rate were decreased significantly in experimental group (P = 0.04 and 0.04). Extensive peritoneal metastasis and other organ metastasis rates had no significant difference between two groups. In the experimental group, 1-, 3-, and 5-year survival rates were higher than in the control group (95.92 vs 87.50 %, 77.55 vs 64.42 %, and 56.12 vs 40.38 %), which had significant difference. Disease-free survival (DFS) of the experimental group was higher than that of the control group (χ (2) = 5.00, P = 0.025). CONCLUSIONS: Intraperitoneal implantation of sustained-release 5-fluorouracil is safe for advanced colorectal cancer during radical resection, which can reduce locoregional recurrence rate and liver metastasis rate. The long-term efficacy was reliable, and long-term survival and disease-free survival rate can be improved.


Asunto(s)
Antineoplásicos/administración & dosificación , Colectomía , Neoplasias del Colon/terapia , Fluorouracilo/administración & dosificación , Neoplasias del Recto/terapia , Neoplasias del Colon/mortalidad , Neoplasias del Colon/patología , Preparaciones de Acción Retardada , Supervivencia sin Enfermedad , Implantes de Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Cavidad Peritoneal , Neoplasias del Recto/mortalidad , Neoplasias del Recto/patología , Tasa de Supervivencia , Resultado del Tratamiento
13.
PLoS One ; 10(5): e0127557, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26010608

RESUMEN

CD44 as one of the most putative stem cell markers plays a key role in many cellular processes, including cancer cell growth and migration. Functional single nucleotide polymorphisms (SNPs) of CD44 may modulate its gene functions and thus cancer risk. In the current study, we investigated if polymorphisms in the 3'-untranslated region (UTR) of CD44 are associated with increased susceptibility to colorectal cancer (CRC) by conducting a case-control study of 946 CRC patients and 989 cancer-free controls. Three polymorphisms (rs13347C/T, rs10836347C/T, rs11821102G/A) in the 3'-UTR of CD44 were genotyped. We found that the variant genotypes (CT and TT) of rs13347 (adjusted odds ratio (OR)=1.79, 95% confidence interval (CI)=1.50-2.17) increased an individual's susceptibility to CRC, compared with rs13347CC homozygous genotypes. We also found that CRC patients with the CT/TT genotype had a 1.6-fold increased risk for developing advanced (stage III + IV) CRC. Furthermore, functional assays showed that the C to T base change at rs13347C/T disrupts the binding site for the microRNA hsa-mir-509-3p, thereby increasing CD44 transcriptional activity and expression level. These findings suggest that the rs13347C/T in microRNA binding site may be potential biomarkers for genetic susceptibility to CRC.


Asunto(s)
Neoplasias Colorrectales/genética , Predisposición Genética a la Enfermedad , Receptores de Hialuranos/genética , MicroARNs/genética , Polimorfismo de Nucleótido Simple , Alelos , Pueblo Asiatico/genética , Sitios de Unión/genética , Estudios de Casos y Controles , China , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad
14.
Int J Mol Med ; 35(5): 1317-22, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25738796

RESUMEN

Colorectal cancer, also known as colon cancer is the most devastating malignancy worldwide. Previous studies have reported that Nit2, a member of the nitrilase superfamily, is a potential tumor suppressor, although its function remains elusive in colon cancer. In the present study, we employed an RNA interference lentivirus system to silence endogenous NIT2 expression in the colon cancer cell line, HCT116. The knockdown efficiency was determined by RT-qPCR and western blot analysis. The depletion of NIT2 markedly inhibited colon cancer cell proliferation and colony formation and induced cell cycle arrest in the G0/G1 phase, as shown by MTT assay, colony formation assay and flow cytometric analysis, respectively. Further investigation with an intracellular signaling array demonstrated that the depletion of NIT2 triggered the apoptosis of colon cancer cells through the caspase-3 and poly(ADP-ribose) polymerase (PARP) pathways. Our findings suggest that NIT2 may be an oncogene in human colon cancer and may thus serve as a promising therapeutic target for the treatment of colon cancer.


Asunto(s)
Aminohidrolasas/genética , Caspasa 3/metabolismo , Neoplasias del Colon/genética , Neoplasias del Colon/metabolismo , Regulación Neoplásica de la Expresión Génica , Poli(ADP-Ribosa) Polimerasas/metabolismo , Transducción de Señal , Puntos de Control del Ciclo Celular/genética , Línea Celular Tumoral , Proliferación Celular , Regulación hacia Abajo , Vectores Genéticos/genética , Humanos , Lentivirus/genética , Interferencia de ARN , ARN Mensajero/genética
15.
Biosci Rep ; 34(6): e00161, 2014 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-25370813

RESUMEN

Dysregulation of protein synthesis is emerging as a major contributory factor in cancer development. eIF3D (eukaryotic translation initiation factor 3 subunit D) is one member of the eIF3 (eukaryotic translation initiation factor 3) family, which is essential for initiation of protein synthesis in eukaryotic cells. Acquaintance with eIF3D is little since it has been identified as a dispensable subunit of eIF3 complex. Recently, eIF3D was found to embed somatic mutations in human colorectal cancers, indicating its importance for tumour progression. To further probe into its action in colon cancer, we utilized lentivirus-mediated RNA interference to knock down eIF3D expression in one colon cancer cell line HCT116. Knockdown of eIF3D in HCT116 cells significantly inhibited cell proliferation and colony formation in vitro. Flow cytometry analysis indicated that depletion of eIF3D led to cell-cycle arrest in the G2/M phase, and induced an excess accumulation of HCT116 cells in the sub-G1 phase representing apoptotic cells. Signalling pathways responsible for cell growth and apoptosis have also been found altered after eIF3D silencing, such as AMPKα (AMP-activated protein kinase alpha), Bad, PRAS40 [proline-rich Akt (PKB) substrate of 40 kDa], SAPK (stress-activated protein kinase)/JNK (c-Jun N-terminal kinase), GSK3ß and PARP [poly(ADP-ribose) polymerase]. Taken together, these findings suggest that eIF3D might play an important role in colon cancer progression.


Asunto(s)
Proliferación Celular/genética , Factor 3 de Iniciación Eucariótica/genética , Lentivirus/genética , Interferencia de ARN , Proteínas Quinasas Activadas por AMP , Apoptosis/genética , Western Blotting , Neoplasias del Colon/genética , Neoplasias del Colon/metabolismo , Neoplasias del Colon/patología , Factor 3 de Iniciación Eucariótica/metabolismo , Fase G1/genética , Puntos de Control de la Fase G2 del Ciclo Celular/genética , Regulación Neoplásica de la Expresión Génica , Vectores Genéticos/genética , Glucógeno Sintasa Quinasa 3 , Glucógeno Sintasa Quinasa 3 beta , Células HCT116 , Células HEK293 , Humanos , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Poli(ADP-Ribosa) Polimerasas/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal/genética , Proteína Letal Asociada a bcl
16.
Arch Med Sci ; 10(4): 651-60, 2014 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-25276147

RESUMEN

INTRODUCTION: A FEW STUDIES HAVE REPORTED AN ASSOCIATION BETWEEN NADP(H): quinine oxidoreductase 1 (NQO1) C609T polymorphism and susceptibility to colorectal cancer (CRC). However, the results were inconsistent rather than conclusive. We performed a meta-analysis to examine this association in various populations. MATERIAL AND METHODS: Eligible articles were identified by a search of several databases up until June 30, 2013. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the strength of the association. RESULTS: Overall, 14 case-control studies with 4,461 cases and 5,474 controls were included in this meta-analysis. The results indicated that the NQO1 C609T polymorphism was significantly associated with CRC susceptibility (summary ORs (95% CIs): 1.30 (1.07-1.59) for CT vs. CC, 1.64 (1.15-2.33) for TT vs. CC, 1.34 (1.10-1.64) for TT/CT vs. CC, and 1.43 (1.10-1.87) for TT vs. CT/CC). Subgroup analyses indicated that the T allele was significantly associated with CRC susceptibility in both Asians and Caucasians, and was also observed in high quality studies and hospital-based case-control studies. Specifically, we found a positive association between the NQO1 C609T polymorphism and CRC susceptibility in smokers, but not in non-smokers. CONCLUSIONS: The results of this meta-analysis suggest that the NQO1 C609T polymorphism significantly contributes to increased susceptibility to CRC in both Asians and Caucasians.

17.
ScientificWorldJournal ; 2014: 703804, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25215329

RESUMEN

Due to changes in lifestyle, particularly changes in dietary habits, colorectal cancer (CRC) increased in recent years despite advances in treatment. Nearly one million new cases diagnosed worldwide and half a million deaths make CRC a leading cause of cancer mortality. In the present study, we aimed to investigate the role of myotubularin-related phosphatase 3 (MTMR3) in CRC cell growth via lentivirus-mediated small interfering RNA (siRNA) transduction in human colon cancer cell lines HCT116 and SW1116. The effect of MTMR3 knockdown on cell growth was evaluated by MTT, colony formation, and flow cytometry assays. The effect of MTMR3 knockdown on cell apoptosis was evaluated by flow cytometry with Annexin V/7-AAD double staining. The activation of apoptotic markers, Bad and PARP, was detected using Intracellular Signaling Array. Knockdown of MTMR3 resulted in a significant reduction in cell proliferation in both HCT116 and SW1116 cells. Moreover, knockdown of MTMR3 led to S phase cell cycle arrest. Furthermore, knockdown of MTMR3 induced cell apoptosis via phosphorylation of Bad and cleavage of PARP. These results indicate that MTMR3 may play an important role in the progression of CRC and suggest that siRNA mediated silencing of MTMR3 could be an effective tool in CRC treatment.


Asunto(s)
Neoplasias Colorrectales/metabolismo , Proteínas Tirosina Fosfatasas no Receptoras/metabolismo , Apoptosis/genética , Línea Celular Tumoral , Proliferación Celular , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Técnicas de Silenciamiento del Gen , Silenciador del Gen , Células HCT116 , Humanos , Fosforilación , Poli(ADP-Ribosa) Polimerasas/metabolismo , Proteínas Tirosina Fosfatasas no Receptoras/genética , Interferencia de ARN , Puntos de Control de la Fase S del Ciclo Celular/genética , Ensayo de Tumor de Célula Madre
18.
Zhonghua Zhong Liu Za Zhi ; 32(2): 111-6, 2010 Feb.
Artículo en Chino | MEDLINE | ID: mdl-20403241

RESUMEN

OBJECTIVE: To study the E-CD and Snail expressions in colorectal cancer and their relationship with colorectal cancer invasion, metastasis and prognosis. METHODS: Immunohistochemical staining (EnVision) was used to detect the E-CD and Snail expressions in 30 normal colorectal mucosa, 30 colorectal adenoma and 142 colorectal cancer tissues. RESULTS: E-CD in the normal colorectal mucosa was strongly positive expressed (90.0%), significantly higher than that in colorectal adenomas (63.3%) and colorectal cancer tissues (41.5%). E-CD expression was significantly related to tumor differentiation, invasion depth, vascular invasion, lymph node metastasis and Dukes' stage (P < 0.05), but not to the patients' age, gender, tumor size and tumor histological type (P > 0.05). The 1-, 3- and 5-year survival rates of the E-CD positive patients with colorectal cancer were significantly higher than that in E-CD negative patients. The positive expression rate of Snail in colorectal cancer tissues (52.1%) was significantly higher than that in normal colorectal mucosa (6.7%) and colorectal adenomas (26.7%, P < 0.05). The snail expression was significantly correlated to tumor histological type, differentiation, invasion depth, vascular invasion, lymph node metastasis and Duke's stage (P < 0.05), but not to patients' age, sex and tumor size (P > 0.05). The 1-, 3- and 5-year survival rates of Snail negative patients with colorectal cancer was significantly higher than that in patients with positive expression (P < 0.05). The expressions of E-CD and Snail in colorectal cancer tissues were inversely correlated (P < 0.05). Cox multivariate analysis showed that E-CD and Snail can be used as independent prognostic indicators (P < 0.05). CONCLUSION: E-CD and Snail expressions in colorectal cancer are related to the tumor invasion, metastasis and prognosis. Low expression of E-CD and high expression of Snail are related to the advanced stage, and poor prognosis in colorectal cancer patients. E-CD and Snail can be used as independent prognostic indicators.


Asunto(s)
Cadherinas/metabolismo , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Factores de Transcripción/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Adenocarcinoma Mucinoso/metabolismo , Adenocarcinoma Mucinoso/patología , Adenocarcinoma Papilar/metabolismo , Adenocarcinoma Papilar/patología , Adenoma/metabolismo , Adolescente , Adulto , Anciano , Femenino , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Metástasis Linfática , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , Factores de Transcripción de la Familia Snail , Tasa de Supervivencia , Adulto Joven
19.
Zhonghua Wei Chang Wai Ke Za Zhi ; 11(3): 223-7, 2008 May.
Artículo en Chino | MEDLINE | ID: mdl-18478463

RESUMEN

OBJECTIVE: To investigate the value of using protective new intracolonic drainage in decreasing low colorectal anastomotic leakage. METHODS: One hundred and nineteen cases of rectal cancer accepted low anterior resection were randomly assigned to study group (n=55) and control group (n=64). The study group was added with a new intracolonic drainage composed of biofragmentable anastomosis ring and condom during operation. The control group was added with protective ileostomy during operation. The results of surgery were compared between the two groups. RESULTS: All the cases were followed up over three months and there were no perioperative death. There were no significant differences in physiopathological factors such as age, sex, body type, site of tumor, size of tumor, differentiation of tumor, site of anastomosis, condition of nutrition, concomitant disease between the two groups. In the study group, anastomotic leakage occurred in 4 cases (7.3%), the drainage devices were ablated 18.3 days after operations and there were no drainage-related complications; light anastomotic stenosis occurred in 3 cases (5.5%) three months after operations. Among the cases with leakage, no severe abdominal infection was found, the time of abdominal drainage was 4.8 days, and the amount of abdominal drainage was 12.8 ml/d in primary three days after leakage. In the control group, anastomotic leakage occurred in 7 cases (10.9%), ostomy-related complications occurred in 29 cases (45.3%), anastomotic stenosis occurred in 18 cases (28.1%) and severe anastomotic stenosis occurred in 4 cases (6.3%) after three months. Among the cases with leakage, severe infection occurred in two cases, anastomotic spoiled occurred in one case, the amount of abdominal drainage was 35.4 ml/d in primary three days after leakage, and the time of abdominal drainage was 17.1 days. There was no significant difference in the rate of anastomotic leakage between the two groups (P>0.05). But there were significant differences in the amount of abdominal drainage, the time of abdominal drainage and abdominal infection in the cases of anastomotic leakage (P<0.01). There was significant difference in anastomotic stenosis after three months between the two groups (P<0.01). CONCLUSIONS: The intracolonic drainage is a simple, safe and effective method in protecting low colorectal anastomotic leakage, and avoiding harmful results caused by anastomotic leakage. Compared with protective ileostomy, intracolonic drainage can avoid stomy-related physical mental suffering and complications, the rate of later anastomotic stenosis is less, and the time of abdominal drainage is shorter in the cases with leakage.


Asunto(s)
Drenaje/métodos , Complicaciones Posoperatorias/prevención & control , Neoplasias del Recto/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Anastomosis Quirúrgica/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recto/cirugía
20.
Zhonghua Wei Chang Wai Ke Za Zhi ; 10(6): 543-5, 2007 Nov.
Artículo en Chino | MEDLINE | ID: mdl-18000776

RESUMEN

OBJECTIVE: To evaluate the value of reoperation for local recurrence of rectal carcinoma. METHODS: The data of 62 cases with post-operative local recurrence of rectal carcinoma were analyzed retrospectively. RESULTS: All the 62 patients received reoperation. Thirty two of those patients were treated with radical resection (16 patients combined multiple organ resection), 6 palliative resection, 11 colostomy, and 13 laparatomy only. The 1-, 3- and 5-year survival rates in the patients accepted radical resection were 90.6%, 59.4% and 18.8% respectively. But in patients undergone palliative resection and combined therapy, survival time was 6-24 months with median survival time of 16 months. The patients, accepted laparatomy and intra-abdominal chemotherapy, all died within 2-14 months postoperatively. For patients with postoperative recurrence time >5 years, <2 years and 2-5 years, the reoperation resection rates were 100%(11/11), 62.9%(22/35), and 31.3%(5/16) respectively, and there were significant differences among 3 groups (P<0.01). The rate of reoperation resection of pure local recurrence was 80.0%(32/40). The rate of reoperation resection of local recurrence, associated with near organ invasion, was 27.3%(6/22). The difference was significant(P<0.01). The reoperation resection rate of first operation with Dixon or Miles was 61.9%(26/42) and 30.0%(6/20), and the difference was significant as well(P<0.05). CONCLUSIONS: The recurrence of rectal carcinoma still needs positive operation in order to prolong the survival time and improve the quality of life of the patient. First operative procedure, post-operative recurrence time and recurrence type are important factors of reoperative resection.


Asunto(s)
Recurrencia Local de Neoplasia/cirugía , Neoplasias del Recto/patología , Neoplasias del Recto/cirugía , Reoperación , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Estudios Retrospectivos , Tasa de Supervivencia , Adulto Joven
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