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1.
Int J Clin Exp Pathol ; 8(9): 11157-63, 2015.
Article in English | MEDLINE | ID: mdl-26617836

ABSTRACT

PURPOSE: KLF17 belongs to the Sp/KLF zinc-finger protein family as a regulator in tumor development. However, its expression and biologic function has remained unclear in EC. METHODS: The esophageal carcinoma tissue samples and adjacent normal tissues were obtained from the Second Hospital of Hebei Medical University. Immunohistochemistry, Western blot, and transfection were applied to evaluate the expression and clinical significance of KLF17 in esophageal cancer. RESULTS: In this study, we showed that KLF17 was overexpressed in esophageal normal samples compared to the cancer. Moreover, KLF17 was upregulated at lymph node non-metastatic cancer tissues when compared to metastatic cancer tissues. KLF17 overexpression decreased EC cell proliferation, migration and invasion ability. In contrast, the knockdown of KLF17 increased EC cell proliferation, migration and invasion ability. CONCLUSION: These results suggest that KLF17 inhibits tumor development and may serve as a potential therapeutic target.


Subject(s)
Biomarkers, Tumor/metabolism , Carcinoma/metabolism , Cell Movement , Esophageal Neoplasms/metabolism , Transcription Factors/metabolism , Biomarkers, Tumor/genetics , Carcinoma/genetics , Carcinoma/secondary , Cell Line, Tumor , Cell Proliferation , China , Down-Regulation , Esophageal Neoplasms/genetics , Esophageal Neoplasms/pathology , Female , Gene Expression Regulation, Neoplastic , Hospitals, University , Humans , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Invasiveness , RNA Interference , Time Factors , Transcription Factors/genetics , Transfection
2.
Am J Transl Res ; 7(8): 1390-403, 2015.
Article in English | MEDLINE | ID: mdl-26396670

ABSTRACT

MicroRNAs (miRNAs) are small, non-coding RNAs which can function as oncogenes or tumor suppressor genes in human cancers. In the present study, we demonstrated that the expression ofmiR-133a was dramatically decreased in examined esophageal squamous cell carcinoma (ESCC) cell lines and clinical ESCC tissue samples. Additionally, miR-133a expression was inversely correlated with tumor progression in ESCCs. We have found that over-expression of miR-133a significantly suppressed the proliferation, migration and invasion of ESCC cells in vitro. miR-133a over-expression also significantly suppressed the aggressive phenotype of ESCC in vivo, suggesting that miR-133a may function as a novel tumor suppressor. Further studies indicated that the EMT-related transcription factor Sox4 was a direct target gene of miR-133a, evidenced by the direct binding of miR-133a with the 3'UTR of Sox4. Notably, the EMT marker E-cadherin or vimentin, a downstream of Sox4, was also down-regulated or upregulated upon miR-133a treatment. We have also shown that over-expressing or silencing Sox4 was able to elevate or inhibit the migration and invasion of ESCC cells, similar to the effect of miR-133a on the ESCC cells. Moreover, knockdown of Sox4 reversed the enhanced migration and invasion mediated by anti-miR-133a. These results demonstrate that miR-133a acts as a tumor suppressor in ESCC through targeting Sox4 and the EMT process. miR-133a may serve as a potential target in the treatment of human esophageal cancer.

3.
Int J Clin Exp Pathol ; 8(7): 8048-56, 2015.
Article in English | MEDLINE | ID: mdl-26339371

ABSTRACT

MicroRNAs (miRNAs) are small, non-coding RNAs of endogenous origin. Accumulating studies have shown aberrant miRNA expression plays an important role in many tumor types. However, the mechanisms by which miRNAs regulate esophageal squamous cell carcinoma (ESCC) development remain poorly understood. In the present study, we assayed expression level of miR-192 in ESCC tissues and cell lines by real-time PCR, and defined the target gene and biological function by luciferase reporter assay, Western blot and apoptosis assay. We first verified that the expression level of miR-192 was significantly increased in ESCC tissues and cancer cells. Moreover, miR-192 over-expression inhibited cells apoptosis and promoted ESCC cells proliferation. We further demonstrated that miR-192 directly targeted 3'-UTR of Bim gene, and inhibited its protein expression. Importantly, Bim could reduce ESCC cells apoptosis ability induced by miR-192. These data suggest an important role of miR-192 in the molecular etiology of ESCC and implicate the potential application of miR-192 in ESCC therapy.


Subject(s)
Apoptosis Regulatory Proteins/metabolism , Apoptosis , Carcinoma, Squamous Cell/metabolism , Cell Proliferation , Esophageal Neoplasms/metabolism , Membrane Proteins/metabolism , MicroRNAs/metabolism , Proto-Oncogene Proteins/metabolism , 3' Untranslated Regions , Apoptosis Regulatory Proteins/genetics , Bcl-2-Like Protein 11 , Binding Sites , Blotting, Western , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology , Cell Line, Tumor , Esophageal Neoplasms/genetics , Esophageal Neoplasms/pathology , Esophageal Squamous Cell Carcinoma , Female , Gene Expression Regulation, Neoplastic , Genes, Reporter , Humans , Male , Membrane Proteins/genetics , MicroRNAs/genetics , Middle Aged , Proto-Oncogene Proteins/genetics , Real-Time Polymerase Chain Reaction , Signal Transduction , Time Factors , Transfection
4.
Tumour Biol ; 35(6): 6039-46, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24622886

ABSTRACT

The aim of this study is to investigate the possible roles of runt-related transcription factor 3 (RUNX3) and ß-catenin in the carcinogenesis of sporadic colorectal tubular adenomas. The expression of the RUNX3 and ß-catenin proteins was evaluated by immunohistochemistry in 23 normal colorectal mucosa (NCM), 81 sporadic colorectal tubular adenomas with different dysplasias (SCTA-D) (mild n=33, moderate n=23, and severe n=25 dysplasia), and 48 sporadic colorectal tubular adenomas with cancerous changes (SCTA-Ca). RUNX3 methylation was assessed by methylation-specific polymerase chain reaction (MSP), combined with laser capture microdissection (LCM), in 17 NCM, 41 SCTA-D (mild n=15, moderate n=12, and severe n=14 dysplasia), and 17 SCTA-Ca tissues. Compared to NCM (82.6 %), RUNX3 in SCTA-D (54.3 %) and SCTA-Ca (27.1 %) was significantly downregulated (P<0.05). In NCM, SCTA-D, and SCTA-Ca, the incidence of positive expression for ß-catenin was 13.0, 60.5, and 79.2 %, respectively. A statistically significant difference was observed (P<0.05). RUNX3 levels were markedly higher in adenoma with mild dysplasia (75.8 %) and moderate dysplasia (60.9 %) than in adenoma with severe dysplasia (20.0 %) (both with P<0.05). Likewise, the expression of ß-catenin in severe dysplasia adenoma was 84.0 %, which was significantly higher than that in mild dysplasia adenoma (39.4 %). An inverse correlation was found between the protein expression of RUNX3 and ß-catenin in SCTA-D and SCTA-Ca (P<0.05). MSP results showed that RUNX3 methylation in NCM, SCTA-D, and SCTA-Ca was 5.9, 17.1, and 41.2 %, respectively, with a statistically significant difference between NCM and SCTA-Ca (P<0.05). However, no significant difference of RUNX3 methylation was observed among different dysplasia groups. RUNX3 and ß-catenin play important roles in the carcinogenesis of sporadic colorectal tubular adenomas. In addition, hypermethylation of RUNX3 can downregulate its expression.


Subject(s)
Adenoma/etiology , Colorectal Neoplasms/etiology , Core Binding Factor Alpha 3 Subunit/physiology , beta Catenin/physiology , Adenoma/chemistry , Adenoma/pathology , Cell Transformation, Neoplastic , Colorectal Neoplasms/chemistry , Colorectal Neoplasms/pathology , Core Binding Factor Alpha 3 Subunit/analysis , Core Binding Factor Alpha 3 Subunit/genetics , DNA Methylation , Humans , Promoter Regions, Genetic , Wnt Signaling Pathway , beta Catenin/analysis
5.
PLoS One ; 8(12): e84944, 2013.
Article in English | MEDLINE | ID: mdl-24391982

ABSTRACT

Dickkopf-1 (DKK1) is an inhibitor of the Wnt/ß-catenin signaling pathway. However, the role of DKK1 in the progression of non small cell lung cancer (NSCLC) is not fully understood. In this study, RT-PCR and Western blot were used to examine the expression of DKK1 in a panel of ten human NSCLC cell lines and NSCLC tissues. DKK1 expression was highly transactivated in the great majority of these cancer lines. The expression of DKK1 was upregulated on both mRNA and protein levels in NSCLC tissues compared with the adjacent normal lung tissues. Immunohistochemistry and immunofluoresence revealed that DKK1 was mainly distributed in the cytoplasm in both carcinoma tissues and cell lines. DKK1 protein expression was also evaluated in paraffin sections from 102 patients with NSCLC by immunohistochemistry, and 65(63.73%)tumors were DKK1 positive. Relative analysis showed a significant relationship between DKK1 positive expression and lymph node metastasis(P<0.05). Patients with DKK1-positive tumors had poorer DFS than those with negative ESCC (5-year DFS; 15.4% versus 27%, P = 0.007). To further explore the biological effects of DKK1 in NSCLC cells, we over-expressed DKK1 in NSCLC 95C cell using eukaryotic expression vector pCMV-Tab-2b and performed a knockdown of DKK1 in LTEP-a-2 cell using a short hairpin RNA expression vector pSilencer 5.1. DKK1 did not have any effect on proliferation, but seemed to play a role in migration and invasion capability. Overexpression of DKK1 promotes migratory and invasive activity of 95C, while DKK1 knockdown resulted in the suppression of migration and invasion potentials of LTEP-a-2 cell. Taken together, these results indicate that DKK1 may be a crucial regulator in the progression of NSCLC. DKK1 might be a potential therapeutic target in NSCLC.


Subject(s)
Carcinoma, Non-Small-Cell Lung/genetics , Gene Expression Regulation, Neoplastic/physiology , Intercellular Signaling Peptides and Proteins/metabolism , Lymphatic Metastasis/genetics , Neoplasm Invasiveness/genetics , Blotting, Western , Cell Line, Tumor , DNA Primers/genetics , Fluorescent Antibody Technique , Gene Expression Regulation, Neoplastic/genetics , Genetic Vectors , Humans , Immunohistochemistry , Intercellular Signaling Peptides and Proteins/genetics , Kaplan-Meier Estimate , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction
6.
Zhonghua Zhong Liu Za Zhi ; 34(6): 446-9, 2012 Jun.
Article in Chinese | MEDLINE | ID: mdl-22967447

ABSTRACT

OBJECTIVE: To evaluate the H. pylori and Epstein-Barr virus infection in cardiac and distal gastric adenocarcinoma tissues in residents in Cixian county, a high risk area of esophageal cancer in Hebei province, and to explore the putative role of H. pylori and Epstein-Barr virus infection in the carcinogenesis of adenocarcinoma at different subsites of stomach. METHODS: H. pylori and Epstein-Barr virus latent membrane protein 1 (EBV-LMP1) immunopositivities were determined by Elivision(TM) plus immunohistochemical staining in 190 gastric adenocarcinoma tissues including 144 cases of cardiac adenocarcinoma and 46 cases of distal gastric adenocarcinoma. The relationship between H. pylori and Epstein-Barr virus infection and the subsite, Laurén type as well as other clinicopathological features of gastric adenocarcinoma were analyzed. RESULTS: No significant difference was found between the H. pylori detection rates in cardiac and distal gastric adenocarcinomas(56.9% vs. 65.2%, P > 0.05). The detection rate of H. pylori in intestinal type was significantly higher than that in the diffuse type distal gastric adenocarcinomas (71.8% vs. 28.6%, P < 0.05). No positive expression of EBV-LMP1 was found in the gastric adenocarcinomas in this study. CONCLUSIONS: No significant differences in H. pylori and EBV-LMP1 infections were found between cardiac and distal gastric adenocarcinomas in Cixian county. H. pylori infection is related with the intestinal type of distal gastric adenocarcinoma.


Subject(s)
Adenocarcinoma , Cardia , Epstein-Barr Virus Infections/pathology , Helicobacter Infections/pathology , Stomach Neoplasms , Adenocarcinoma/microbiology , Adenocarcinoma/pathology , Adenocarcinoma/virology , Aged , China , Female , Helicobacter pylori/isolation & purification , Humans , Male , Middle Aged , Stomach Neoplasms/microbiology , Stomach Neoplasms/pathology , Stomach Neoplasms/virology , Viral Matrix Proteins/metabolism
7.
Zhonghua Zhong Liu Za Zhi ; 31(10): 773-7, 2009 Oct.
Article in Chinese | MEDLINE | ID: mdl-20021832

ABSTRACT

OBJECTIVE: To evaluate the expression of vascular endothelial growth factor C (VEGF-C) and peroxisome proliferators-activated receptors (PPARgamma) in extrahepatic cholangioadenocarcinoma (EHCAC) and to elucidate its correlation with clinicopathological factors and their significance in prognosis. METHODS: The expressions of PPARgamma and VEGF-C were detected by immunohistochemistry in 69 cases of EHCAC, 12 cases of non-tumor bile duct epithelium, and their relationship to clinicopathological parameters and follow-up were analyzed. RESULTS: The positive rate of PPARgamma expression in 69 cases of EHCAC was 59.4%, significantly higher than that in 12 cases of non-tumor bile duct epithelium (0%), (P < 0.01). The positive rate of VEGF-C in 69 cases of EHCAC was 84.1%, also significantly higher than 16.7% in 12 cases of benign bile duct epithelium (P < 0.05). PPARgamma expression was associated with clinical TNM stage and lymph node metastasis. VEGF-C expression was associated with lymph node metastasis. Cox analysis results showed that portal vein and/or hepatic artery invasion, lymph node metastasis and VEGF-C expression were independent prognostic factors of EHCAC (P < 0.05). CONCLUSION: PPARgamma expression may play an important role during tumorigenesis of extrahepatic cholangioadenocarcinoma. The expressions of PPARgamma and VEGF-C are significantly correlated with the clinicopathological characteristics and biological behavior of EHCAC. Expression of VEGF-C is an independent prognosis factors in EHCAC. The detection of PPARgamma and VEGF-C is valuable for evaluation of prognosis of EHCAC.


Subject(s)
Bile Duct Neoplasms/metabolism , Bile Ducts, Intrahepatic , Cholangiocarcinoma/metabolism , PPAR gamma/metabolism , Vascular Endothelial Growth Factor C/metabolism , Adult , Aged , Aged, 80 and over , Bile Duct Neoplasms/pathology , Cholangiocarcinoma/pathology , Female , Follow-Up Studies , Humans , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Staging , Proportional Hazards Models , Survival Rate
8.
Zhonghua Zhong Liu Za Zhi ; 30(12): 905-9, 2008 Dec.
Article in Chinese | MEDLINE | ID: mdl-19173990

ABSTRACT

OBJECTIVE: To investigate the variation in expression of ARHI, STAT3 and E2F1 and the correlation among them during carcinogenesis of ovarian serous carcinoma. METHODS: Immunohistochemical staining was used to detect the expression of ARHI, STAT3 and E2F1 in samples of 25 normal ovaries, 35 ovarian serous cystadenomas, 18 borderline serous cystadenomas and 56 ovarian serous carcinomas. The variation in expression of the three genes and relationship among them were analyzed. RESULTS: ARHI expression was detected in 22 of 25 (88.0%) normal ovaries and 30 of 35 (85.7%) cystadenomas, but only in 10 of 18 (55.6%) borderline serous cystadenomas and 22 of 56 (39.3%) ovarian serous carcinomas, significantly lower than that in the normal ovaries and ovarian serous cystadenomas (P < 0.05). STAT3 expression was found in 14 of 18 (77.8%) borderline serous cystadenomas and 49 of 56 (87.5%) ovarian serous carcinomas, significantly higher than that in the normal ovaries and ovarian serous cystadenomas (P < 0.05). To compare with E2F1 expression in the normal ovaries, serous cystadenomas and borderline serous cystadenomas, E2F1 expression in 46 of 56 (82.1%) ovarian serous carcinomas was significantly higher (P < 0.05). It was found that the expression of ARHI was inversely correlated with that of STAT3 and E2F1. CONCLUSION: Our findings indicate that ARHI expression is down-regulated, but STAT3 and E2F1 expressions are up-regulated, with an inverse correlation between ARHI and STAT3 in the carcinogenesis of ovarian serous carcinoma.


Subject(s)
Cystadenocarcinoma, Serous/metabolism , E2F1 Transcription Factor/metabolism , Ovarian Neoplasms/metabolism , STAT3 Transcription Factor/metabolism , rho GTP-Binding Proteins/metabolism , Adult , Aged , Cystadenocarcinoma, Serous/pathology , Cystadenoma, Serous/metabolism , Cystadenoma, Serous/pathology , Female , Gene Expression Regulation, Neoplastic , Humans , Immunohistochemistry , Middle Aged , Ovarian Neoplasms/pathology , Ovary/metabolism , Ovary/pathology
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