RESUMEN
The highly conserved ribosomal protein L34 (RPL34) has been reported to play an essential role in the progression of diverse malignancies. RPL34 is aberrantly expressed in multiple cancers, although its significant in colorectal cancer (CRC) is currently unclear. Here, we demonstrated that RPL34 expression was higher in CRC tissues than in normal tissues. Upon RPL34 overexpression, the ability of proliferation, migration, invasion, and metastasis of CRC cells were significantly enhanced in vitro and in vivo. Furthermore, high expression of RPL34 accelerated cell cycle progression, activated the JAK2/STAT3 signaling pathway, and induced the epithelial-to-mesenchymal transition (EMT) program. Conversely, RPL34 silencing inhibited the CRC malignant progression. Utilizing immunoprecipitation assays, we identified the RPL34 interactor, the cullin-associated NEDD8-dissociated protein 1 (CAND1), which is a negative regulator of cullin-RING ligases. CAND1 overexpression reduced the ubiquitin level of RPL34 and stabilized RPL34 protein. CAND1 silencing in CRC cells resulted in a decrease in the ability of proliferation, migration, and invasion. CAND1 overexpression promoted CRC malignant phenotypes and induced EMT, and RPL34 knockdown rescued CAND1-induced CRC progression. In summary, our study indicates that RPL34 acts as a mediator, is stabilized by CAND1, and promotes proliferation and metastasis, in part, through the activation of the JAK2/STAT3 signaling pathway and induction of EMT in CRC.
Asunto(s)
Neoplasias Colorrectales , Proteínas Cullin , Humanos , Proteínas Cullin/genética , Proteínas Cullin/metabolismo , Regulación hacia Abajo , Movimiento Celular/genética , Transducción de Señal , Proliferación Celular/genética , Neoplasias Colorrectales/metabolismo , Línea Celular Tumoral , Transición Epitelial-Mesenquimal/genética , Regulación Neoplásica de la Expresión Génica , Metástasis de la Neoplasia , Janus Quinasa 2/genética , Janus Quinasa 2/metabolismo , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/metabolismoRESUMEN
The karyopherin α2 subunit gene (KPNA2), an oncogene, is involved in metabolic reprogramming in cancer. This study aimed to explore the function of KPNα2 in the growth and glycolysis in colon cancer (CC) cells. Genes from the Oncomine database that were differentially expressed in multiple CC types were screened. Bioinformatics analysis suggested that KPNA2 was highly expressed in CC, and consequently, high expression of KPNA2 was detected in the CC cell lines. Down-regulation of KPNA2 reduced viability and DNA-replication ability, and increased apoptosis of HCT116 and LoVo cells. It also reduced glucose consumption, extracellular acidification rate, and the ATP production in cells. Centromere protein A (CENPA) was confirmed as an upstream transcription activator of KPNA2. There was significant H3K27ac modification in the promoter region of KPNA2. CENPA primarily recruited histone acetyltransferase general control of amino acid synthesis (GCN)-5 to the promoter region of KPNA2 to induce transcription activation. Overexpression of either CENPA or GCN-5 blocked the role of short hairpin KPNα2 and restored growth and glycolysis in CC cells. To conclude, the findings from this study suggest that CENPA recruits GCN-5 to the promoter region of KPNA2 to induce KPNα2 activation, which strengthens growth and glycolysis in, and augments the development of, CC.
Asunto(s)
Proteína A Centromérica/fisiología , Neoplasias del Colon/genética , alfa Carioferinas/genética , Animales , Neoplasias del Colon/metabolismo , Neoplasias del Colon/patología , Metabolismo Energético/genética , Células HCT116 , Células HEK293 , Humanos , Redes y Vías Metabólicas/genética , Ratones , Ratones Endogámicos NOD , Ratones SCID , Activación Transcripcional , Células Tumorales Cultivadas , alfa Carioferinas/metabolismoRESUMEN
AIM: To review the application of nutrition support in patients after surgery for colorectal cancer, and to propose appropriate nutrition strategies. METHODS: A total of 202 consecutive surgical patients admitted to our hospital with a diagnosis of colon cancer or rectal cancer from January 2010 to July 2010, meeting the requirements of Nutrition Risk Screening 2002, were enrolled in our study. Laboratory tests were performed to analyze the nutrition status of each patient, and the clinical outcome variables, including postoperative complications, hospital stay, cost of hospitalization and postoperative outcome, were analyzed. RESULTS: The "non-risk" patients who did not receive postoperative nutrition support had a higher rate of postoperative complications than patients who received postoperative nutrition support (2.40 ± 1.51 vs. 1.23 ± 0.60, P = 0.000), and had a longer postoperative hospital stay (23.00 ± 15.84 d vs. 15.27 ± 5.89 d, P = 0.009). There was higher cost of hospitalization for patients who received preoperative total parenteral nutrition (TPN) than for patients who did not receive preoperative TPN (62 713.50 ± 5070.66 RMB Yuan vs. 43178.00 ± 3596.68 RMB Yuan, P = 0.014). Applying postoperative enteral nutrition significantly shortened postoperative fasting time (5.16 ± 1.21 d vs. 6.40 ± 1.84 d, P = 0.001) and postoperative hospital stay (11.92 ± 4.34 d vs. 15.77 ± 6.03 d, P = 0.002). The patients who received postoperative TPN for no less than 7 d had increased serum glucose levels (7.59 ± 3.57 mmol/L vs. 6.48 ± 1.32 mmol/L, P = 0.006) and cost of hospitalization (47 724.14 ± 16 945.17 Yuan vs. 38 598.73 ± 8349.79 Yuan, P = 0.000). The patients who received postoperative omega-3 fatty acids had a higher rate of postoperative complications than the patients who did not (1.33 ± 0.64 vs. 1.13 ± 0.49, P = 0.041). High level of serum glucose was associated with a high risk of postoperative complications of infection. CONCLUSION: Appropriate and moderate nutritional intervention can improve the postoperative outcome of colorectal cancer patients.
Asunto(s)
Neoplasias Colorrectales/dietoterapia , Neoplasias Colorrectales/cirugía , Apoyo Nutricional , Complicaciones Posoperatorias , Neoplasias Colorrectales/patología , Ácidos Grasos Omega-3/administración & dosificación , Femenino , Humanos , Masculino , Estado Nutricional , Periodo Posoperatorio , Resultado del TratamientoRESUMEN
AIM: To investigate the protective effect of melatonin on liver after intestinal ischemia-reperfusion injury in rats. METHODS: One hundred and fifty male Wistar rats, weighing 190-210 g, aged 7 wk, were randomly divided into melatonin exposure group, alcohol solvent control group and normal saline control group. Rats in the melatonin exposure group received intraperitoneal (IP) melatonin (20 mg/kg) 30 min before intestinal ischemia-reperfusion (IR), rats in the alcohol solvent control group received the same concentration and volume of alcohol, and rats in the normal saline control group received the same volume of normal saline. Serum samples were collected from each group 0.5, 1, 6, 12, and 24 h after intestinal IR. Levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured with an auto-biochemical analyzer. Serum TNF-alpha was tested by enzyme-linked immunosorbent assay (ELISA). Malondialdehyde (MDA) in liver was detected by colorimetric assay. Pathological changes in liver and immunohistochemical straining of ICAM-1 were observed under an optical microscope. RESULTS: The levels of ALT measured at various time points after intestinal IR in the melatonin exposure group were significantly lower than those in the other two control groups (P < 0.05). The serum AST levels 12 and 24 h after intestinal IR and the ICAM-1 levels (%) 6, 12 and 24 h after intestinal IR in the melatonin exposure group were also significantly lower than those in the other two control groups (P < 0.05). CONCLUSION: Exotic melatonin can inhibit the activity of ALT, AST and TNF-alpha, decrease the accumulation of MDA, and depress the expression of ICAM-1 in liver after intestinal IR injury, thus improving the liver function.
Asunto(s)
Antioxidantes/uso terapéutico , Intestinos , Hepatopatías/etiología , Hepatopatías/prevención & control , Melatonina/uso terapéutico , Daño por Reperfusión/complicaciones , Alanina Transaminasa/metabolismo , Animales , Antioxidantes/farmacología , Aspartato Aminotransferasas/metabolismo , Molécula 1 de Adhesión Intercelular/metabolismo , Intestinos/trasplante , Hígado/efectos de los fármacos , Hígado/metabolismo , Hepatopatías/metabolismo , Masculino , Malondialdehído/metabolismo , Melatonina/farmacología , Modelos Animales , Ratas , Ratas Wistar , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
BACKGROUND: Survivin is a new and important gene in the regulation of apoptosis. It is very important to explore the effect of the expression of survivin protein caused by ischemia-reperfusion (IR) injury. The effect of IR injury caused by ischemic preconditioning (IP) on the liver in rats and the relation between the protective effect of IP and the expression of survivin are unclear. METHODS: One hundred and fifty male Wistar rats (weighing 190-210 g, aged 6-7 weeks) were divided into three groups at random: ischemic preconditioning (IP), ischemia-reperfusion (IR) and sham-operation (SO). Sample specimens were collected from each group at 6, 12, 24, 48, and 72 hours after reperfusion. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured by an automatic biochemical analyzer. Malondialdehyde (MDA) in liver tissue was measured. Pathological changes in the liver and immunohistochemical staining for survivin were determined with an optical microscope. RESULTS: The ALT levels in the IP and IR groups after reperfusion at each time were higher than those in the SO group (P<0.05), whereas after reperfusion for 6 and 12 hours, the ALT levels in the IP group were lower than those in the IR group (P<0.05). The AST levels in all IP and IR groups were higher than those in the SO group (P<0.05), whereas after reperfusion for 12, 24, 48 and 72 hours, the AST levels in the IP group were lower than those in the IR group (P<0.05). The MDA concentrations after reperfusion in the IP group were lower than those in the IR group (P<0.05), though the MDA concentrations in the IP and IR groups increased in contrast to those in the SO group after reperfusion at each time (P<0.05). After reperfusion for 12, 24, 48 and 72 hours, the number of survivin-positive cells was larger in the IP and IR groups than in the SO group (P<0.05). After reperfusion for 12, 24, and 48 hours the number of survivin-positive cells in the IP group increased compared with that in the IR group (P<0.05). CONCLUSIONS: IR increases the protein expression of survivin in liver tissue. IP inhibits the accumulation of MDA, advances the expressive phase of survivin protein in hepatic tissue, and improves liver function.