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1.
J Cell Mol Med ; 27(17): 2547-2561, 2023 09.
Article in English | MEDLINE | ID: mdl-37488750

ABSTRACT

SMAD4 is a tumour suppressor and an important regulator of tumour immune scape which is downregulated in cholangiocarcinoma (CCA). STING1 is a vital sensing factor of abnormal DNA; however, the correlation between SMAD4 and STING1 and the role of the SMAD4-STING1 interaction in the progression of CCA have not yet been evaluated. Public database was analysed to reveal the expression of SMAD4 and STING1. A cohort comprising 50 iCCA, 113 pCCA and 119 dCCA patients was assembled for the study. Immunohistochemistry was employed to evaluate the expression levels of STING1 and SMAD4. In vitro transwell and CCK8 assays, along with luciferase reporter assay, were conducted to analyse the potential regulatory mechanisms of SMAD4 on the expression of STING1. Expression of SMAD4 and STING1 were downregulated in CCA tumours and STING1 expression correlated with SMAD4 expression. The overexpression of SMAD4 was found to suppress the migration, invasion and proliferation capabilities of CCA cells; whereas, the knockdown of SMAD4 enhanced these abilities. Furthermore, it was observed that SMAD4 translocated into the nucleus following TGF-ß1 stimulation. Knockdown of SMAD4 resulted in the inhibition of STING1 transcriptional activity, whereas the overexpression of SMAD4 promoted the transcriptional activity of STING1. Clinically, low STING1 and SMAD4 expression indicated poor prognosis in CCA, and simultaneously low expression of STING1 and SMAD4 predicts poorer patient survival. SMAD4 regulates the expression of STING1 through its transcription regulating function. Dual low expression of STING1 and SMAD4 had more power in predicting patient survival. These results indicate that SMAD4-silenced CCA may downregulate its STING1 expression to adapt to the immune system.


Subject(s)
Bile Duct Neoplasms , Cholangiocarcinoma , Smad4 Protein , Humans , Bile Duct Neoplasms/genetics , Bile Duct Neoplasms/pathology , Bile Ducts, Intrahepatic/metabolism , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Cholangiocarcinoma/metabolism , Gene Expression Regulation, Neoplastic , Smad4 Protein/genetics , Smad4 Protein/metabolism
2.
Front Oncol ; 13: 1140103, 2023.
Article in English | MEDLINE | ID: mdl-37064120

ABSTRACT

Cholangiocarcinoma (CCA) is a highly malignant tumor of the hepatobiliary system that has failed to respond to many traditional therapies to a certain extent, including surgery, chemotherapy and radiotherapy. In recent years, the new therapeutic schemes based on immunology have fundamentally changed the systemic treatment of various malignant tumors to a certain extent. In view of the immunogenicity of CCA, during the occurrence and development of CCA, some immunosuppressive substances are released from cells and immunosuppressive microenvironment is formed to promote the escape immune response of its own cells, thus enhancing the malignancy of the tumor and reducing the sensitivity of the tumor to drugs. Some immunotherapy regimens for cholangiocarcinoma have produced good clinical effects. Immunotherapy has more precise characteristics and less adverse reactions compared with traditional treatment approaches. However, due to the unique immune characteristics of CCA, some patients with CCA may not benefit in the long term or not benefit at all after current immunotherapy. At present, the immunotherapy of CCA that have been clinically studied mainly include molecular therapy and cell therapy. In this article, we generalized and summarized the current status of immunotherapy strategies including molecular therapy and cell therapy in CCA in clinical studies, and we outlined our understanding of how to enhance the clinical application of these immunotherapy strategies.

3.
Cancer Cell Int ; 23(1): 46, 2023 Mar 16.
Article in English | MEDLINE | ID: mdl-36927769

ABSTRACT

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Its invasiveness and ability to metastasize contributes to an extremely high patient mortality. However, the molecular mechanisms that underlie the characteristics of HCC progression are not well understood. BRF2 has been shown to be an oncogene in a number of tumors; however, its role in HCC has not yet been thoroughly examined. In this study, we identified and validated BRF2 as an oncogene in HCC, providing a new insight into HCC pathogenesis and therapeutic possibilities. We showed that BRF2 expression was significantly upregulated in HCC cell lines and tissues, while BRF2 depletion suppressed HCC metastasis and invasion. We then examined the upstream regulation of BRF2 and identified miR-409-3p as being predicted to bind to the 3' UTR of BRF2. We used a luciferase activity assay and functional verification to show that BRF2 is downregulated by miR-409-3p. Finally, we used bioinformatic analysis to show that BRF2 may be related to early HCC development through the Wnt/ß-catenin signaling pathway.

4.
Front Oncol ; 12: 1075685, 2022.
Article in English | MEDLINE | ID: mdl-36568193

ABSTRACT

Background: Hepatocellular carcinoma (HCC) is a well-described complication of Budd-Chiari syndrome (BCS). However, the risk factors of BCS in developing HCC and clinical characteristics and imaging features of BCS-associated HCC is still to be determined. Methods: Data from 113 consecutive patients with primary BCS in Qilu hospital were retrospectively studied. The clinical features of 12 HCC patients associated with BCS were also analyzed. Chi-square analysis was performed to analyze the differences in clinical characteristics. The treatment regime and CT imaging features of BCS-associated HCC were also illustrated. Results: 113 consecutive patients admitted to our hospital between January 2009 and June 2016 with a primary diagnosis of BCS were enrolled. 10.6% (12/113) was diagnosed with HCC. The BCS patients were mainly male gender with an average age of 49.2 years. Symptom duration longer than one year exhibited decreased serum ALT and AST and increased ascites ratio. BCS-associated HCC patients were presented with IVC block and stricture of the hepatic venous outflow tract. Patients with HCC were older and showed elevated serum AST and total bilirubin. Most nodules of HCC located in the right posterior lobe with heterogeneous enhancement during the arterial phase and washout during the delayed phase. Conclusions: The results indicate that BCS patients with IVC block and stricture of hepatic venous outflow tract seem to be associated with HCC. BCS associated HCC nodules exhibited irregular and heterogeneous enhancement in the arterial phase and washout on the delayed phase.

5.
Front Immunol ; 13: 1049812, 2022.
Article in English | MEDLINE | ID: mdl-36389727

ABSTRACT

Biliary tract cancers (BTCs), including cholangiocarcinoma and gallbladder carcinoma, originate from the biliary epithelium and have a poor prognosis. Surgery is the only choice for cure in the early stage of disease. However, most patients are diagnosed in the advanced stage and lose the chance for surgery. Early diagnosis could significantly improve the prognosis of patients. Bile has complex components and is in direct contact with biliary tract tumors. Bile components are closely related to the occurrence and development of biliary tract tumors and may be applied as biomarkers for BTCs. Meanwhile, arising evidence has confirmed the immunoregulatory role of bile components. In this review, we aim to summarize and discuss the relationship between bile components and biliary tract cancers and their ability as biomarkers for BTCs, highlighting the role of bile components in regulating immune response, and their promising application prospects.


Subject(s)
Bile Duct Neoplasms , Biliary Tract Neoplasms , Humans , Bile , Biliary Tract Neoplasms/diagnosis , Biliary Tract Neoplasms/pathology , Biomarkers , Bile Ducts, Intrahepatic/pathology , Immunity
6.
Exp Ther Med ; 21(3): 236, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33603844

ABSTRACT

Semaphorin 3B (SEMA-3B), which belongs to the semaphorin family, has an important role in cell apoptosis and inhibition of angiogenesis. A previous study by our group revealed that SEMA-3B was downregulated in tumor tissues of patients with hepatocellular carcinoma (HCC) and exerts anti-motility and anti-invasion effects on tumor cells. However, the serum levels of SEMA-3B and their clinical significance have remained elusive; therefore, the aim of the present study was to monitor its expression in HCC and investigate its clinical significance. ELISA was used to determine the serum levels of SEMA-3B in 132 patients with HCC and 57 healthy individuals. The association between SEMA-3B and clinicopathological parameters was investigated. Serum SEMA-3B was indicated to be significantly decreased in patients with HCC as compared with that in the controls (P<0.05) and it was negatively associated with tumor size (P=0.039), encapsulation (P=0.002) and TNM stage (P=0.034). The prognosis of patients with low expression of SEMA-3B was poor. In conclusion, the results of the present study revealed that serum SEMA-3B is decreased in HCC and is negatively associated with prognosis; therefore, it may be used as a prognostic marker in HCC.

8.
J Cancer ; 11(6): 1412-1423, 2020.
Article in English | MEDLINE | ID: mdl-32047548

ABSTRACT

Aims: Hilar cholangiocarcinoma (HCCA) is a tumour with high malignancy, low surgical resection potential, and a poor prognosis. Ecotropic Viral Integration site 1 (EVI1) is a transcriptional regulator that has been proven to be associated with tumourigenesis and progression in many human solid tumours. However, the expression of EVI1 and its role in HCCA progression remain unclear. The aim of this study was to clarify the association between EVI1 expression and clinical outcomes in patients with HCCA. Methods: The expression of EVI1 in HCCA tissue samples and cell lines was examined by quantitative real-time PCR (qRT-PCR), Western blotting, and immunohistochemistry (IHC). Kaplan-Meier analysis was used for survival analysis. A log-rank test was performed for univariate analysis of survival, and a Cox regression model was utilized for multivariate analysis of survival. Cell proliferation was measured by cell counting kit-8 (CCK-8), colony formation, and 5-ethynyl-2'-deoxyuridine (EdU) assays. The cell cycle was evaluated by flow cytometry. Cell apoptosis was detected by flow cytometry and a terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labelling (TUNEL) assay. In vivo tumour growth was observed for xenografts in nude mice. Results: EVI1 expression was upregulated in HCCA tissue samples and correlated with a poor prognosis. In clinical specimens, the expression of EVI1 correlated with tumour histological grade and tumour size. Knocking down EVI1 expression reduced HCCA cell proliferation, blocked cell cycle progression, and promoted apoptosis in vitro and in vivo. Furthermore, we found that EVI1 could regulate the AKT signalling pathway by regulating PTEN levels in HCCA. Conclusion: Our data revealed that EVI1 played important roles in HCCA tumourigenesis and development. Our findings suggest that EVI1 may be a potentially useful therapeutic target in HCCA.

10.
Oncogene ; 38(6): 868-880, 2019 02.
Article in English | MEDLINE | ID: mdl-30177842

ABSTRACT

Perihilar cholangiocarcinoma (PHCCA) is the most common type of cholangiocarcinoma with low resection rate and high morbidity. The study of PHCCA biomarkers made progresses slowly compared with intrahepatic cholangiocarcinoma because of surgical complexity and low possibility of radical surgery, which resulted in the difficulty of specimen obtainment. To screen and identify new biomarkers in PHCCA, we constructed a retrospective cohort with 121 PHCCA patients and a prospective cohort consisting of 64 PHCCA patients, and screened the candidate biomarkers by immunohistochemistry and quantified PCR. In our study, expression of high mobility group box 1 (HMGB1) was demonstrated to be significantly associated with microvascular density (MVD) and unfavorable prognosis of PHCCA in both retrospective and prospective study. Moreover, HMGB1 concentrations in bile and serum of PHCCA patients and healthy controls were detected and compared. Postoperative serum HMGB1 and reflux cholangitis indicated recurrence and unfavorable prognosis of PHCCA. With experiments in vitro and in vivo, we demonstrated that intracellular HMGB1 could be released from PHCCA cells and induce invasion and angiogenesis with LPS stimulation. VEGFR2 expression in vessel endothelial cells was upregulated by the released HMGB1 from PHCCA, resulting in the ectopic angiogenesis. In conclusion, intracellular HMGB1 could be released from PHCCA cells and promote angiogenesis via elevating VEGFR2 in vessel endothelial cells. High expression of HMGB1 was associated with MVD and poor prognosis in clinical analyzation. Postoperative serum HMGB1 and cholangitis could predict high recurrence and unfavorable prognosis.


Subject(s)
Bile Duct Neoplasms , HMGB1 Protein/blood , Klatskin Tumor , Neoplasm Proteins/blood , Neovascularization, Pathologic , Bile Duct Neoplasms/blood , Bile Duct Neoplasms/mortality , Bile Duct Neoplasms/surgery , Disease-Free Survival , Endothelial Cells/metabolism , Endothelial Cells/pathology , Female , Humans , Klatskin Tumor/blood , Klatskin Tumor/mortality , Klatskin Tumor/surgery , Male , Neovascularization, Pathologic/blood , Neovascularization, Pathologic/mortality , Neovascularization, Pathologic/surgery , Prospective Studies , Survival Rate
11.
J Cell Mol Med ; 22(11): 5596-5606, 2018 11.
Article in English | MEDLINE | ID: mdl-30160357

ABSTRACT

Fibroblast growth factor receptor 2 (FGFR2) was demonstrated to correlate to the progression and prognosis of intrahepatic cholangiocarcinoma (ICC) by numerous evidences. However, as a well-recognized suppressor of FGFR2 signalling, the clinical significance of Sprouty (SPRY) family of ICC has not been investigated. In our study, the expressions of SPRY1-4 in 20 pairs of fresh tumour tissues were detected with qPCR, and in 108 cases of paraffin-embedded tissues with immunohistochemistry. The prognostic value of SPRY family in ICC was estimated with univariate analysis and multivariate analysis. As a result, SPRY2 was identified as an independent prognostic biomarker predicting favourable prognosis of ICC. High SPRY2 expression was correlated with good differentiation of ICC. With silencing SPRY2 expression, we demonstrated that SPRY2 could suppress FGFR2-induced ERK phosphorylation, migration, invasion and epithelial-mesenchymal transition (EMT) under FGF1 stimulation. By overexpressing SPRY2-wide type or SPRY2-Y55F, the tyrosine-55 of SPRY2 was demonstrated to be essential in suppressing ERK phosphorylation, tumour invasion and EMT of ICC cells. In conclusion, SPRY2 was correlated with favourable prognosis of ICC via suppressing FGFR2-induced ERK phosphorylation, invasion and EMT. The phosphorylation of SPRY2-Y55 was required in this tumour-suppressing function of SPRY2.


Subject(s)
Cholangiocarcinoma/genetics , Intracellular Signaling Peptides and Proteins/genetics , Membrane Proteins/genetics , Prognosis , Receptor, Fibroblast Growth Factor, Type 2/genetics , Adult , Aged , Aged, 80 and over , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Cholangiocarcinoma/epidemiology , Cholangiocarcinoma/pathology , Disease Progression , Disease-Free Survival , Epithelial-Mesenchymal Transition/genetics , Female , Gene Expression Regulation, Neoplastic/genetics , Humans , Male , Middle Aged , Phosphorylation , Signal Transduction/genetics , Tissue Array Analysis
13.
Medicine (Baltimore) ; 96(12): e6350, 2017 Mar.
Article in English | MEDLINE | ID: mdl-28328818

ABSTRACT

Todani classification is extensively used to guide the surgical strategy of choledochal cysts, but no systematic investigations on the distal management of intrapancreatic choledochal cysts have been conducted. This study reports the distal classification and management of choledochal cysts in adults based on the relation between the cyst and pancreatic duct. Patients with choledochal cyst who underwent operation, including distal management, in our department from January 2009 to December 2014 were retrospectively reviewed. Patients presenting symptoms, coexisting diseases, surgical treatment, perioperative complications, and long-term follow-up according to the distal classification of choledochal cyst were analyzed. A total of 54 patients with choledochal cyst were included in the present retrospective study. Based on the distal classification of choledochal cyst, 39 patients (72.22%) were type 1, 13 patients (24.07%) were type 2, and 2 patients (3.70%) were type 3. Thirty-nine type 1 patients and 10 type 2 patients underwent excision of intrapancreatic choledochal cyst or bile duct. Three type 2 patients received excision of distal cylindrical cyst and papilla, followed by pancreatic duct plasty with duodenum mucosa. One type 3 patient underwent endoscopic sphincteroplasty, and another type 3 patient underwent transduodenal sphincteroplasty. After the operation, 11 patients (20.37%, 11/54) had short-term perioperative complications. The long-term follow-up results showed that the satisfactory rate (excellent and good outcomes) was 95.83%. Current distal classification of choledochal cysts could provide a more targeted strategy for complete excision to eliminate potential dead space within the pancreas, protect the pancreatic duct, and prevent reoperation.


Subject(s)
Choledochal Cyst/classification , Choledochal Cyst/surgery , Adolescent , Adult , Aged , Female , Follow-Up Studies , Humans , Male , Middle Aged , Pancreatic Diseases/classification , Pancreatic Diseases/surgery , Postoperative Complications/epidemiology , Retrospective Studies , Treatment Outcome , Young Adult
14.
Int J Hyperthermia ; 33(3): 255-262, 2017 May.
Article in English | MEDLINE | ID: mdl-27817240

ABSTRACT

PURPOSE: The aim of this study was to compare the results of microwave ablation (MWA) and hepatic resection (HR) when combined with pericardial devascularisation plus splenectomy (PCDV) for the treatment of patients with cirrhosis complicated by small hepatocellular carcinoma (HCC) and oesophageal variceal bleeding (EVB). MATERIALS AND METHODS: Between 2001 and 2013, 73 patients (median age 53.2 years, 67% male) with small HCC and concomitant EVB who underwent MWA or HR for HCC and PCDV for cirrhotic portal hypertension were selected retrospectively for inclusion in this study. The overall survival curves and recurrence-free survival curves were calculated using the Kaplan-Meier method and compared using log-rank tests. Multivariate analysis was performed using the Cox regression model. RESULTS: The 1-, 3- and 5-year overall survival rates were 95.2%, 71.4% and 38.1% and 96.7%, 53.3% and 43.3% for the HR and MWA groups, respectively; these did not differ significantly between the two groups. However, patients in the HR group had more post-operative complications (52.3% vs. 13.7%; p = 0.002). Multivariate analysis identified albumin and bilirubin levels and tumour size to be statistically significant and independent prognostic factors for overall survival, while BCLC stage was associated with poor recurrence-free survival. Furthermore, albumin levels were shown to be an independent predictive factor for post-operative complications. CONCLUSIONS: For patients with small HCC and concomitant EVB, MWA plus PCDV may reduce the incidence of post-operative complications relative to and provide similar therapeutic benefits as HR plus PCDV, especially for patients with low albumin levels.

15.
BMC Cancer ; 16(1): 880, 2016 11 11.
Article in English | MEDLINE | ID: mdl-27836008

ABSTRACT

BACKGROUND: High-mobility group protein box1 (HMGB1) is a pivotal factor in the development and progression of many types of tumor. Its role in hepatocellular carcinoma (HCC), and especially its correlation with intratumoral and peritumoral macrophage infiltration, remains obscure. We analyzed the potential roles and prognostic value of HMGB1 and explored the correlation between HMGB1 and macrophage infiltration in HCC using clinical samples. METHODS: We reviewed clinicopathological and follow-up data on a cohort of 149 patients with HCC complicated with Hepatitis B-related cirrhosis. We measured the expression of HMGB1 and CD68 in tumoral and peritumoral liver tissues after curative resection and assessed the impacts of the tumor-associated macrophage (TAM) count and HMGB1 expression on clinicopathologic characteristics, overall survival (OS), and recurrence-free survival (RFS). RESULTS: Ninety-four of the patients had elevated tumoral HMGB1 expression and 59 of the patients had elevated peritumoral HMGB1 expression, compared to only 4 patients with elevated peritumoral HMGB1 expression in 36 pateints with Hepatitis B virus (HBV)-negative HCC without liver cirrhosis (p < 0.001). The peritumoral HMGB1 expression levels were correlated with tumor invasiveness, BCLC stage, and recurrence. The degree of TAM infiltration was higher in peritumoral tissues with high HMGB1 expression than in peritumoral tissues with low HMGB1 expression (p < 0.001). There was no significant difference in TAM infiltration between tumoral tissues with high and low HMGB1 expression. Kaplan-Meier analysis showed that intratumoral HMGB1 overexpression was associated with poor OS, but not with RFS. High peritumoral HMGB1expression and TAM count, which correlated positively with tumor size and BCLC stage, were independent prognostic factors for OS (p < 0.001 and p = 0.017, respectively) and RFS (p = 0.002 and p = 0.024, respectively). Multivariate analyses indicated peritumoral HMGB1 expression (p = 0.014) and TAM count (p = 0.037), as well as tumor differentiation (p = 0.026), to be independent significant prognostic factors for RFS. CONCLUSIONS: High HMGB1 expression in peritumoral liver tissues correlated with peritumoral macrophage infiltration and had prognostic value in HCC, suggesting that peritumoral HMGB1 might show promise as a new biomarker to predict HCC progression.


Subject(s)
Carcinoma, Hepatocellular/metabolism , HMGB1 Protein/metabolism , Hepatitis B/metabolism , Liver Cirrhosis/metabolism , Liver Neoplasms/metabolism , Macrophages/physiology , Aged , Carcinoma, Hepatocellular/immunology , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/virology , Cell Movement , Disease-Free Survival , Female , Gene Expression Regulation, Neoplastic , Hepatitis B/immunology , Hepatitis B/mortality , Humans , Kaplan-Meier Estimate , Liver Cirrhosis/immunology , Liver Cirrhosis/mortality , Liver Cirrhosis/virology , Liver Neoplasms/immunology , Liver Neoplasms/mortality , Liver Neoplasms/virology , Male , Middle Aged , Multivariate Analysis , Prognosis , Proportional Hazards Models , Tumor Microenvironment/immunology , Up-Regulation
16.
Sci Rep ; 6: 28229, 2016 06 20.
Article in English | MEDLINE | ID: mdl-27320390

ABSTRACT

Although cholecystectomy has been reported to be associated with increased risk of developing hepatocellular carcinoma (HCC), the association between cholecystectomy and prognosis of HCC patients underwent curative resection has never been examined. Through retrospective analysis of the data of 3933 patients underwent curative resection for HCC, we found that cholecystectomy was an independent prognostic factor for recurrence-free survival (RFS) of patients at early stage (BCLC stage 0/A) (p = 0.020, HR: 1.29, 95% CI: 1.04-1.59), and the 1-, 3-, 5-year RFS rates for patients at early stage were significantly worse in cholecystectomy group than in non-cholecystectomy group (80.5%, 61.8%, 52.0% vs 88.2%, 68.8%, 56.8%, p = 0.033). The early recurrence rate of cholecystectomy group was significantly higher than that of non-cholecystectomy group for patients at early stage (59/47 vs 236/333, p = 0.007), but not for patients at advanced stage (BCLC stage C) (p = 0.194). Multivariate analyses showed that cholecystectomy was an independent risk factor for early recurrence (p = 0.005, HR: 1.52, 95% CI: 1.13-2.03) of early stage HCC, but not for late recurrence (p = 0.959). In conclusion, cholecystectomy is an independent predictor for early recurrence and is associated with poorer RFS of early stage HCC. Removal of normal gallbladder during HCC resection may be avoided for early stage patients.


Subject(s)
Carcinoma, Hepatocellular/pathology , Cholecystectomy/adverse effects , Gallbladder Neoplasms/surgery , Gallbladder/surgery , Liver Neoplasms/pathology , Neoplasm Recurrence, Local/pathology , Disease-Free Survival , Female , Humans , Male , Middle Aged , Retrospective Studies , Risk Factors
20.
IUBMB Life ; 67(3): 191-201, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25873402

ABSTRACT

Chemoresistance of colon cancer cells to the chemotherapeutics is still a main obstacle in treatment of this malignancy. The microRNA (miRNA) mediated chemosensitivity regulation in colon cancer cells is still largely unknown. Here we constructed a fluorouracil (5-Fu) resistant SW480 cell line (SW480/5-Fu) and discovered that miRNA miR-494 was down-regulated in the drug resistant cells compared with the parental cells. miR-494 level was found to be correlated with 5-Fu sensitivity in colon cancer cells, and artificial alteration of miR-494 affects the sensitivity of colon cancer cell lines to 5-Fu. miR-494 also promoted apoptosis of colon cancer cells at present of 5-Fu. Importantly, as a regulatory enzyme in the 5-Fu catabolic pathway, DPYD was confirmed to be a direct target of miR-494 through the interaction of miR-494 and its binding site within DPYD 3' untranslated region (3'UTR). miR-494 also negatively regulated endogenous DPYD expression in SW480 cells. Overexpression or knockdown of DPYD could attenuate miR-494 mediated 5-Fu sensitivity regulation, suggesting the dependence of DPYD regulation in miR-494 activity. miR-494 inhibited SW480/5-Fu derived xenograft tumors growth in vivo at present of 5-Fu. Thus, we concluded that in colon cancer cells, tumor suppressor miR-494 enhanced 5-Fu sensitivity via regulation of DPYD expression.


Subject(s)
Colonic Neoplasms/drug therapy , Colonic Neoplasms/genetics , Dihydrouracil Dehydrogenase (NADP)/genetics , Drug Resistance, Neoplasm/genetics , Fluorouracil/pharmacology , MicroRNAs/genetics , 3' Untranslated Regions , Animals , Antimetabolites, Antineoplastic/pharmacology , Apoptosis/drug effects , Apoptosis/genetics , Cell Line, Tumor/drug effects , Colonic Neoplasms/pathology , Dihydrouracil Dehydrogenase (NADP)/metabolism , Female , Gene Expression Regulation, Neoplastic/drug effects , Humans , Mice, Nude , MicroRNAs/metabolism , Xenograft Model Antitumor Assays
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