Jin Bai

Xuzhou Medical College, Wu-hsien, Jiangsu Sheng, China

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Publications (19)65.27 Total impact

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    ABSTRACT: CHIP (c-terminal Hsp70-interacting protein) is an E3 ligase which may play different roles in different cancers. The elucidation of the VHL-HIF-1α(hypoxia inducible factor-1α)-VEGF (vascular endothelial growth factor) pathway has led to the development of targeted therapy in renal cell carcinoma (RCC). However, little is known about the role of CHIP and the relationship between CHIP and VEGF-VEGFR2 (VEGF receptor 2) pathway in RCC. In this study, we found that the expression of CHIP was downregulated and significantly correlated with pT status (P = 0.022) and TNM stage (P = 0.022) in 304 RCC and 35 normal renal tissues using tissue microarray. Moreover, low expression of CHIP is a strong and independent negative prognostic value for RCC. In vitro, CHIP negatively regulated RCC cell migration, invasion and angiogenesis. In addition, ELISA tests showed that restoration of CHIP inhibited, while knockdown promoted, the secreted level of VEGF. Furthermore, western blot indicated that the VEGFR2 protein level was reduced after CHIP overexpression. Our findings demonstrate for the first time that CHIP may be involved in RCC angiogenesis through regulating VEGF secretion and expression of VEGFR2. CHIP may serve as promising prognostic biomarker of angiogenesis and may constitute a potential therapeutic target in RCC.
    Scientific Reports 05/2015; 5:9774. DOI:10.1038/srep09774 · 5.58 Impact Factor
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    ABSTRACT: PIN2/TRF1-interacting telomerase inhibitor 1 (PinX1) is a novel cloned gene which has been identified as a major haploinsufficient tumor suppressor essential for maintaining telomerase activity, the length of telomerase and chromosome stability. This study explored the clinical significance and biological function of PinX1 in human clear cell renal cell carcinoma (ccRCC). The clinical relevance of PinX1 in ccRCC was evaluated using tissue microarray and immunohistochemical staining in two independent human ccRCC cohorts. Our data demonstrated that PinX1 expression was dramatically decreased in ccRCC tissues compared with normal renal tissues and paired adjacent non-tumor tissues. Low PinX1 expression was significantly correlated with depth of invasion, lymph node metastasis and advanced TNM stage in patients, as well as with worse overall and disease-specific survival. Cox regression analysis revealed that PinX1 expression was an independent prognostic factor for ccRCC patients. Moreover, PinX1 inhibited the migration and invasion of ccRCC by suppressing MMP-2 expression and activity via NF-κB-dependent transcription in vitro. In vivo studies confirmed that PinX1 negatively regulated ccRCC metastasis and the expression of MMP-2 and NF-κB-p65. These findings indicate that PinX1 suppresses ccRCC metastasis and may serve as a ccRCC candidate clinical prognostic marker and a potential therapeutic target.
    Oncotarget 05/2015; · 6.63 Impact Factor
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    ABSTRACT: Autophagy is a major catabolic process that degrades and recycles cytosolic components in autophagosomes, which fuse with lysosomes. This process enables starving cells to sustain their energy requirements and metabolic states, thus facilitating their survival, especially in cancer pathogenesis. The regulation of autophagy is quite intricate. It involves a series of signaling cascades including p53, known as the best-characterized tumor suppressor protein. Recent reports have indicated that p53 plays dual roles in regulating autophagy depending on its subcellular localization. Nuclear p53 facilitates autophagy by transactivating its target genes, whereas cytoplasmic p53 mainly inhibits autophagy through extranuclear, transcription-independent mechanisms. The relationship between autophagy and neoplasia is complicated. It may be intrinsically associated with the functional status of p53, but this is not clearly elucidated. This review focuses on the role of p53 as a master regulator of autophagy. We conclude that the contextual role of autophagy in cancer, which could be switched by p53 status, is expected to be developed into a new anticancer therapeutic approach. Copyright © 2015. Published by Elsevier Ireland Ltd.
    Cancer letters 04/2015; 363(2). DOI:10.1016/j.canlet.2015.04.014 · 5.02 Impact Factor
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    ABSTRACT: Background PinX1 (PIN2/TRF1-interacting telomerase inhibitor 1) was suggested to be correlated with tumor progression. This study was designed to evaluate the role of PinX1 in human breast cancer. Methods To evaluate the function of PinX1 in breast cancer, we used a tissue microarray (TMA) of 405 human breast cancer patients and immunohistochemistry to analyze the correlation between PinX1 expression and clinicopathologic variables and patient survival. We also detected the abilities of cell migration and invasion in breast cancer by performing cell migration and invasion assay, gelatin zymography and western blot analysis. Lastly, we set up the nude mice model by Tail vein assay to exam the functional role of PinX1 in breast cancer metastasis. Results We found that low PinX1 expression was associated with lymph node metastasis (P = 0.002) and histology grade (P = 0.001) in patients, as well as with poorer overall and disease-specific survival (P = 0.010 and P = 0.003, respectively). Moreover, we identified that PinX1 inhibited the migration and invasion of breast cancer by suppressing MMP-9 expression and activity via NF-κB-dependent transcription in vitro. Finally, our mice model confirmed that PinX1 suppressed breast cancer metastasis in vivo. Conclusions Our data revealed that low PinX1 expression was an independent negative prognostic factor for breast cancer patients. These findings suggested that PinX1 might be function as a tumor metastasis suppressor in the development and progression of breast cancer by regulating the NF-κB/MMP-9 signaling pathway, and might be a prognostic marker as well as a therapeutic target for breast cancer. Electronic supplementary material The online version of this article (doi:10.1186/s12943-015-0332-2) contains supplementary material, which is available to authorized users.
    Molecular Cancer 03/2015; 14(1). DOI:10.1186/s12943-015-0332-2 · 5.40 Impact Factor
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    ABSTRACT: PinX1 induces apoptosis and suppresses cell proliferation in some cancer cells, and the expression of PinX1 is frequently decreased in some cancer and negatively associated with metastasis and prognosis. However, the precise roles of PinX1 in gliomas have not been studied. In this study, we found that PinX1 obviously reduced the gliomas cell proliferation through regulating the expressions of cell cycle-relative molecules to arrest cell at G1 phase and down-regulating the expression of component telomerase reverse transcriptase (hTERT in human), which is the hardcore of telomerase. Moreover, PinX1 could suppress the abilities of gliomas cell wound healing, migration and invasion via suppressing MMP-2 expression and increasing TIMP-2 expression. In conclusion, our results suggested that PinX1 may be a potential suppressive gene in the progression of gliomas.
    Medical Oncology 03/2015; 32(3):545. DOI:10.1007/s12032-015-0545-7 · 2.06 Impact Factor
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    ABSTRACT: The neutrophil-to-lymphocyte ratio (NLR) is a strong predictor of mortality in patients with colorectal, lung, gastric cancer, pancreatic and metastatic renal cell carcinoma. We here evaluated whether preoperative NLR is an independent prognostic factor for non-metastatic renal cell carcinoma (RCC). Data from 327 patients who underwent curative or palliative nephrectomy were evaluated retrospectively. In preoperative blood routine examination, neutrophils and lymphocytes were obtained. The predictive value of NLR for non-metastatic RCC was analyzed. The NLR of 327 patients was 2.72±2.25. NLR <1.7 and NLR ≥1.7 were classified as low and high NLR groups, respectively. Chi-square test showed that the preoperative NLR was significantly correlated with the tumor size (P=0.025), but not with the histological subtype (P=0.095)and the pT stage (P=0.283). Overall survival (OS) and disease-free survival (DFS) were assessed using the Kaplan-Meier method. Effects of NLR on OS (P=0.007) and DFS (P=0.011) were significant. To evaluate the independent prognostic significance of NLR, multivariate COX regression models were applied and identified increased NLR as an independent prognostic factor for OS (P=0.015), and DFS (P=0.019). Regarding patient survival, an increased NLR represented an independent risk factor, which might reflect a higher risk for severe cardiovascular and other comorbidities. An elevated blood NLR may be a biomarker of poor OS and DFS in patients with non-metastatic RCC.
    Asian Pacific journal of cancer prevention: APJCP 01/2015; 16(9):3703-8. · 2.51 Impact Factor
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    ABSTRACT: The aim of this study was to investigate the clinical significance of annexin a1 (ANXA1) and provide molecular evidence to support that decreased ANXA1 expression could enhance cancer migration and invasion in pancreatic ductal adenocarcinoma (PDAC). Immunohistochemistry of a tissue microarray with 162 surgically resected PDAC specimens was performed to examine the expression of ANXA1. We also investigated the relationship between ANXA1 expression and clinicopathological factors and prognosis of PDAC patients. We further studied the role of ANXA1 in PDAC cell proliferation, migration and invasion by cell proliferation assay, migration assay and matrigel invasion assay with reduced ANXA1 expression by RNAi. Western blotting was used to detect matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinase-1 (TIMP-1) expression. We also detected MMP-9 enzyme activity by gelatin zymography. Decreased expression of ANXA1 was significantly associated with poor differentiation, lymph node metastasis and advanced TNM stage of PDAC patients (p<0.05). Moreover, decreased expression of ANXA1 was correlated with poor survival (p<0.05). Furthermore, we found that ANXA1 knockdown inhibited cell proliferation, induced G1 phase cell cycle arrest, increased PDAC cell migration and invasion capacity compared with controls. In addition, Western blotting showed that ANXA1 knockdown increased the MMP-9 protein level and decreased TIMP-1 expression. Gelatin zymography showed that MMP-9 enzyme activity was also elevated. Negative ANXA1 expression is a most unfavorable prognostic factor for PDAC patients. ANXA1 knockdown inhibits cell proliferation by inducing G1 phase cell cycle arrest and increases migration and invasion of PDAC cells through up-regulating MMP-9 expression and activity, implying that ANXA1 may serve as a promising prognostic biomarker and therapeutic target for PDAC.
    Asian Pacific journal of cancer prevention: APJCP 01/2015; 16(7):2719-24. · 2.51 Impact Factor
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    ABSTRACT: Chemotherapy is one of the important methods for treatment in tumors. However, many tumor patients may experience tumor recurrence because of treatment failure due to chemoresistance. Although many signaling pathways could influence chemoresistance of tumor cells, the extracellular signal-regulated kinase 1 and 2 (ERK1/2) pathway has gained significant attention because of its implications in signaling and which has crosstalk with other signaling pathways. Extensive studies conclude that ERK1/2 pathway is responding to chemoresistance in many kinds of malignant tumors. The aim of this review is to discuss on the role of ERK1/2 pathway in chemoresistance and therapy of tumors. A comprehensive understanding of ERK1/2 pathway in chemoresistance of tumors could provide novel avenues for treatment strategies of tumors. Copyright © 2014 Elsevier Ltd. All rights reserved.
    Bioorganic & Medicinal Chemistry Letters 12/2014; 25(2). DOI:10.1016/j.bmcl.2014.11.076 · 2.33 Impact Factor
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    ABSTRACT: Sperm-associated antigen 9 (SPAG9) is a recently characterized oncoprotein involved in the progression of several human malignancies. To elucidate the role of SPAG9 in the development of human prostate cancer (PCa), tissue microarray (TMA) and immunohistochemistry were used to detect the clinical relevance of SPAG9 in PCa tissues. We found that SPAG9 expression was increased in the PCa tissues when compared with the level in the tumor adjacent normal prostate tissues, and increased SPAG9 staining was significantly correlated with TNM stage and tumor grade. We also examined prostate cancer cell motility, invasion and angiogenesis ability following reduced SPAG9 expression by siRNA. Our data showed that knockdown of SPAG9 in prostate cancer cell lines inhibited cell motility and invasion due to the inactivation of metalloproteinase-2 (MMP‑2)/MMP-9 by upregulation of tissue inhibitor of metalloproteinase-1 (TIMP-1)/TIMP-2. Furthermore, downregulation of vascular endothelial growth factor (VEGF) secretion greatly contributed to the reduced ability of angiogenesis. Our data indicate that SPAG9 expression is significantly increased in PCa and it may be involved in the process of prostate cancer cell motility, migration and angiogenesis.
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    ABSTRACT: Breast cancer metastasis suppressor 1 (BRMS1) is a metastasis suppressor gene in several solid tumors. However, the expression and function of BRMS1 in glioma have not been reported. In this study, we investigated whether BRMS1 play a role in glioma pathogenesis. Using the tissue microarray technology, we found that BRMS1 expression is significantly decreased in glioma compared with tumor adjacent normal brain tissue (P<0.01, χ2 test) and reduced BRMS1 staining is associated with WHO stages (P<0.05, χ2 test). We also found that BRMS1 was significantly downregulated in glioma cell lines compared to normal human astrocytes (P<0.01, χ2 test). Furthermore, we demonstrated that BRMS1 overexpression inhibited glioma cell invasion by suppressing uPA, NF-κB, MMP-2 expression and MMP-2 enzyme activity. Moreover, our data showed that overexpression of BRMS1 inhibited glioma cell migration and adhesion capacity compared with the control group through the Src-FAK pathway. Taken together, this study suggested that BRMS1 has a role in glioma development and progression by regulating invasion, migration and adhesion activities of cancer cells.
    PLoS ONE 05/2014; 9(5):e98544. DOI:10.1371/journal.pone.0098544 · 3.53 Impact Factor
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    ABSTRACT: The ERCC1 and ERCC2 genes are important in repairing DNA damage and genomic instability, and are involved in the nucleotide excision repair pathway. We hypothesized that single nucleotide polymorphisms (SNPs) in ERCC1 and ERCC2 are associated with the risk of colorectal cancer in a Chinese population. To test this hypothesis, we genotyped four functional SNPs (ERCC1 Asn118Asn, C8092A, ERCC2 Asp312Asn, and Lys751Gln) in a case-control study with 213 colorectal cancer cases and 240 cancer-free controls. We found that the ERCC1 C8092A polymorphism AA and CA/AA variant genotypes were associated with a significantly increased risk of colorectal cancer, compared with the CC genotype (OR = 2.50, 95% CI = 1.10-5.70 for AA versus CC, and OR = 1.58, 95% CI = 1.08-2.30 for CA/AA versus CC). Furthermore, the effect appeared to be more prominent among men, smokers, drinkers, and patients with rectal cancer. However, no other SNPs were observed for any significant association with colorectal cancer risk. These results suggest that the ERCC1 C8092A polymorphism may contribute to colorectal cancer susceptibility in the Chinese population. Further large and functional studies are needed to confirm our findings.
    Scientific Reports 02/2014; 4:4112. DOI:10.1038/srep04112 · 5.58 Impact Factor
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    ABSTRACT: RUNX3 (runt-related transcription factor-3) has been reported to suppress tumor tumorigenesis and metastasis in different human cancers. In this study, we used tissue microarray (TMA) to determine the significance of RUNX3 in prostate cancer progession. Our results showed ectopic expression of RUNX3 in prostate cancer tissues when compared with tumor adjacent normal prostate tissues, and reduced RUNX3 staining was significantly correlated with TNM stage. Moreover, we demonstrated that RUNX3 overexpression inhibited prostate cancer cell migration and invasion resulting from the elevated upregulation of tissue inhibitor of matrix metalloproteinase-2 (TIMP-2), which subsequently inhibited metalloproteinase-2 (MMP-2) expression and activity in vitro. Knock down of RUNX3 expression broke up the balance of TIMP-2/MMP-2, whereas silence of TIMP-2 resulted in the inhibition of MMP-2 expression in prostate cells. We also showed that restoration of RUNX3 decreased vascular endothelial growth factor (VEGF) secretion and suppressed endothelial cell growth and tube formation. Strikingly, RUNX3 was demonstrated to inhibit tumor metastasis and angiogenesis in vivo. Altogether, our results support the tumor suppressive role of RUNX3 in human prostate cancer, and provide insights into development of targeted therapy for this disease.
    PLoS ONE 01/2014; 9(1):e86917. DOI:10.1371/journal.pone.0086917 · 3.53 Impact Factor
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    ABSTRACT: The carboxyl terminus of Hsp70-interacting protein (CHIP) is a member of E3 ubiquitin ligase, functioning as a link between the chaperone (heat shock protein 70/90) and proteasome systems, playing a vital role in maintaining the protein homeostasis in the cytoplasm. CHIP has been demonstrated to be involved in tumorigenesis, proliferation and invasion in several malignancies, regulating a number of oncogenic proteins. However, CHIP has also been implicated in the modulation of tumor suppressor proteins. The pathogenic mechanism of CHIP expression in human malignancy is not yet clear, and a number of studies have suggested that CHIP may have opposing roles in different cancers. Therefore, many studies have focused on the relationship between CHIP and carcinoma. A literature search focusing on regulation network, biological function and clinical significance of CHIP in connection with its role in cancer development was performed on the MEDLINE databases. CHIP may be a potential diagnostic biomarker and therapeutic target for human cancer, and may play different roles in different human cancers. This inconsistence might be induced by the diversity of CHIP downstream targeting proteins. Therefore, the phenotypes determined by CHIP should be dependent on the function of its specific targets in a specific type of cancer cells. Whether CHIP contributes to tumor progression or suppression in various human cancers remains unclear, suggesting the necessity of further extensive investigation of its role in tumorigenesis.
    Journal of Cancer Research and Clinical Oncology 12/2013; DOI:10.1007/s00432-013-1571-5 · 3.01 Impact Factor
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    ABSTRACT: BRG1, a core component of the SWI/SNF chromatin-remodeling complex, has been implicated in cancer development; however, the biological significance of BRG1 in breast cancer remains unknown. We explored the role of BRG1 in human breast cancer pathogenesis. Using tissue microarray and immunohistochemistry, we evaluated BRG1 staining in 437 breast cancer specimens and investigated its role in breast cancer cell proliferation, migration and invasion. Our Kaplan-Meier survival curves showed that high BRG1 expression is inversely correlated with both overall (P = 0.000) and disease-specific (P = 0.000) 5-year patient survival. Furthermore, we found that knockdown of BRG1 by RNA interference markedly inhibits cell proliferation and causes cessation of cell cycle. This reduced cell proliferation is due to G1 phase arrest as cyclin D1 and cyclin E are diminished whereas p27 is upregulated. Moreover, BRG1 depletion induces the expression of TIMP-2 but reduces MMP-2, thereby inhibiting the ability of cells to migrate and to invade. These results highlight the importance of BRG1 in breast cancer pathogenesis and BRG1 may serve as a prognostic marker as well as a potentially selective therapeutic target.
    PLoS ONE 11/2013; 8(3):e59772. DOI:10.1371/journal.pone.0059772 · 3.53 Impact Factor
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    ABSTRACT: Oncolytic adenoviruses are a novel class of anticancer treatment, based upon their ability to replicate selectively within malignant cells resulting in cell lysis. The replication‑selective adenovirus, ZD55‑IL‑24, was constructed by harboring an E1B‑55 kDa deletion and arming with interleukin-24 (IL-24). The microtubule‑stabilizing drug paclitaxel (PTX) exhibits activity in relapsed cancer. In the present study, the synergistic antitumor effects of the combination of PTX and ZD55‑IL‑24 on breast cancer cells was investigated. The results demonstrated that there were different roles for PTX in the expression of transgenic mRNA and protein. ZD55‑IL‑24 combined with PTX induced marked growth inhibition of MDA‑MB‑231 and Bcap‑37 cells. PTX increased viral uptake and appeared not to alter the replication of ZD55‑IL‑24 in breast cancer cells. Annexin V‑fluorescein isothiocyanate/propidium iodide staining and the Hoechst 33258 assay indicated that ZD55‑IL‑24 induced an increase in the number of apoptotic cells when administered in combination with PTX. It was demonstrated that ZD55‑IL‑24 conjugated with PTX was highly concomitant, and increased proapoptotic proteins levels, activated caspase‑3, -7 and -9 and downregulated anti‑apoptotic proteins. These results suggested that ZD55‑IL‑24 in combination with PTX exhibited a markedly increased cytotoxic and apoptosis‑inducing effect in breast cancer cells. Thus, this chemo‑gene‑viro therapeutic strategy was demonstrated to be superior to conventional chemotherapy or gene‑viro therapy alone.
    Molecular Medicine Reports 09/2013; 8(5). DOI:10.3892/mmr.2013.1680 · 1.48 Impact Factor
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    ABSTRACT: To investigate the prognostic value of tumor-infiltrating regulatory T cells (Tregs) in the distribution of cancer nest, cancer stroma and normal mucosa and FOXP3-positive cancer cells in colon cancer patients after resection. Paraffin blocks of operation resection of primary adenocarcinoma of colon were obtained from ninety patients. The distribution of tumor-infiltrating Tregs was detected by tissue microarray and immunohistochemistry staining technique to evaluate the prognostic effects by Kaplan-Meier and Cox regression analysis using median values as cutoff. The intratumoral Tregs counts were significantly higher than that in corresponding normal mucosa tissues (P < 0.001); the Tregs counts in cancer nest were significantly lower than that in corresponding cancer stroma tissues (P < 0.001); the increased intratumoral Tregs counts were associated with favorable prognosis (P < 0.05); the presence of Tregs in cancer nest was associated with unfavorable prognosis and was an independent prognostic factor for overall survival (P < 0.05). The appearance of FOXP3-positive cancer cells was associated with worse prognosis (P < 0.05). In addition, the frequency of the presence of FOXP3-positive cancer cells was higher in patients with lymphatic invasion (P < 0.001) and lower in patients with early TNM stage (P < 0.01). The higher tumor-infiltrating Tregs counts are closely associated with the improved prognostic effects of colon carcinoma. Tregs play different roles in cancer nest and cancer stroma. And the appearance of Tregs in cancer nest is a promising independent risk factor for overall survival in colon carcinoma. FOXP3-positive cancer cells may also be a risk factor for overall survival in colon carcinoma.
    Journal of Cancer Research and Clinical Oncology 09/2013; 139(11). DOI:10.1007/s00432-013-1500-7 · 3.01 Impact Factor
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    ABSTRACT: RUNX3 (runt-related transcription factor-3) is a known tumor suppressor gene which exhibits potent antitumor activity in several carcinomas. However, little is known about the role of RUNX3 in human renal cell carcinoma (RCC). To investigate the clinical relevance of RUNX3 in RCC patients, immunohistochemistry was performed to detect the clinical relevance of RUNX3 in 75 RCC tissues and paired non-cancerous tissues by using tissue microarray (TMA). We also investigated the role of RUNX3 in RCC cell migration, invasion and angiogenesis. The RUNX3 expression was decreased dramatically in human RCC tissue. The RUNX3 expression was significantly correlated with tumor size (<0.001), depth of invasion (<0.001), and of TNM stage (<0.001). Restoration of RUNX3 significantly decreased renal carcinoma cell migration and invasion capacity compared with controls. In addition, we found that overexpression of RUNX3 reduced the proliferation and tube formation of human umbilical vascular endothelial cells (HUVECs). Gelatin zymography and Western blot showed that RUNX3 expression suppressed matrix metalloproteinase-9 (MMP-9) protein level and enzyme activity. Western blot and ELISA showed that RUNX3 restoration inhibited the expression and secretion of vascular endothelial growth factor (VEGF). Taken together, our studies indicate that decreased expression of RUNX3 in human RCC tissue is significantly correlated with RCC progression. Restoration of RUNX3 expression significantly inhibits RCC cells migration, invasion and angiogenesis. These findings provide new insights into the significance of RUNX3 in migration, invasion and angiogenesis of RCC.
    PLoS ONE 02/2013; 8(2):e56241. DOI:10.1371/journal.pone.0056241 · 3.53 Impact Factor
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    ABSTRACT: The purposes of our study were to elucidate the role of BRG1 in the development of human glioma and to determine the effect of BRG1 on glioma cell growth, migration and invasion. Using tissue microarray and immunohistochemistry, we evaluated BRG1 staining in 190 glioma tissues, 8 normal brain tissues and 8 tumor adjacent normal brain tissues. We studied glioma cell proliferative ability with reduced BRG1 expression by siRNA using CCK-8 cell proliferation assay and cell cycle analysis. We studied the role of BRG1 in glioma cell migration and invasion by cell migration assay and matrigel invasion assay. We performed western blot to detect cyclin D1, cyclin B1 and MMP-2 protein expression. We also detected MMP-2 enzyme activity by gelatin zymography. Our results showed that BRG1 expression was increased in benign tumor and malignant tumor compared with tumor adjacent normal brain tissue (P < 0.01 for both). We did not find any correlation between BRG1 expression and clinicopathological parameters. In addition, we found that knockdown of BRG1 in glioma cell lines inhibits cell growth due to the G1 phase arrest by downregulating cyclin D1. We further demonstrated that silencing of BRG1 in glioma cells inhibited the cell migration and invasion abilities, and downregulation of MMP-2 expression greatly contributed to the reduced cell invasion and migration abilities. Our data indicated that BRG1 expression is significantly increased in human glioma and it may be involved in the process of glioma cell proliferation, migration and invasion.
    Journal of Cancer Research and Clinical Oncology 02/2012; 138(6):991-8. DOI:10.1007/s00432-012-1172-8 · 3.01 Impact Factor
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    ABSTRACT: The aim of this study is to investigate whether the expression of RUNX3 is related to the development of glioma, and the role of RUNX3 in glioma cells growth, invasion and migration. We analyzed the protein expression of RUNX3 by immunohistochemistry in 188 glioma tissues, 8 normal brain tissues and 8 tumor adjacent normal brain tissues using tissue microarray technique. We studied whether RUNX3 restoration can suppress glioma cells growth, invasion and migration by performing MTT cell proliferation assay, matrigel cell invasion assay, wound-healing assay and migration assay. We also detected MMP-2 protein expression and enzyme activity by western blot analysis and gelatin zymography. We found that RUNX3 expression was decreased in benign tumor and malignant tumor compared with tumor adjacent normal brain tissue (P < 0.01 and P < 0.05, respectively). We did not find any correlation between RUNX3 expression and clinicopathological parameters. In addition, we demonstrated that re-expression of RUNX3 in glioma cells resulted in significantly inhibited cell invasion and migration abilities. This reduced cell invasion and migration abilities were due to MMP-2 protein expression and enzyme activity suppression after RUNX3 restoration. Our data indicated that RUNX3 expression is significantly decreased in human glioma, and targeting of the RUNX3 pathway may constitute a potential treatment modality for glioma.
    Journal of Cancer Research and Clinical Oncology 09/2011; 137(12):1823-30. DOI:10.1007/s00432-011-1063-4 · 3.01 Impact Factor