Jun-Nian Zheng

Xuzhou Medical College, Suchow, Jiangsu Sheng, China

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Publications (49)103.19 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Temozolomide (TMZ) is an alkylating agent that is widely used in chemotherapy for cancer. A key mechanism of resistance to TMZ is the overexpression of O(6)-methylguanine-DNA methyltransferase (MGMT). MGMT specifically repairs the DNA O(6)-methylation damage induced by TMZ and irreversibly inactivates TMZ. Regulation of MGMT expression and research regarding the mechanism of TMZ resistance will help rationalize the clinical use of TMZ. In this review, we provide an overview of recent advances in the field, with particular emphasis on MGMT structure, function, expression regulation, and the association between MGMT and resistance to TMZ.
    Molecular Biology Reports 07/2014; · 2.51 Impact Factor
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    ABSTRACT: The aim of our study was to elucidate the role of Rap2B in the development of human suprarenal epithelioma and to investigate the effect of Rap2B on suprarenal epithelioma cells migration and invasion. We use tissue microarray and immunohistochemistry to evaluate Rap2B staining in 75 suprarenal epithelioma tissues and 75 tumor-adjacent normal renal tissues. And the expression of Rap2B protein in human suprarenal epithelioma cells and tissues was detected by western blot simultaneously. The role of Rap2B in suprarenal epithelioma cells migration and invasion was detected by using wound healing assay, cell migration assay, and matrigel invasion assay. After that, we performed western blot analysis and gelatin zymography to detect MMP-2 protein expression and enzyme activity. Our research showed that Rap2B expression was increased in tumor tissues compared with tumor-adjacent normal renal tissues. But no correlation was found between Rap2B expression and clinicopathological parameters. In addition, we found that Rap2B promoted the cell migration and invasion abilities, and Rap2B increased MMP-2 expression and enzyme activity in suprarenal epithelioma cells. Our data indicated that Rap2B expression is significantly increased in human suprarenal epithelioma and Rap2B can promote the cell migration and invasion abilities, which may provide a new target for the treatment of suprarenal epithelioma.
    Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. 06/2014;
  • Yi-Yang Wen, Jun-Nian Zheng, Dong-Sheng Pei
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    ABSTRACT: Introduction: Overexpression of p21-activated kinase 5 (PAK5) is discovered in many tumors, probably due to its regulation in cytoskeleton, antiapoptosis and proliferation. A better understanding of the modulation mechanisms of PAK5 is needed for the development of tumor treatment where current therapeutics is inadequate. Areas covered: This review discusses the current understanding of PAK5 functions as an oncogenic kinase in tumor cellular regulation. Mechanisms of action and molecular pathways involved in cytoskeleton regulation, antiapoptosis and proliferation of tumors are discussed. Expert opinion: PAKs are serine/threonine kinases and downstream effectors for Cdc42 and Rac, the subfamilies of Rho small GTPases. PAK5 shares sequence identities in p21-GTPase-binding domain and kinase domain and is completely different in other regions compared with other PAKs. Overexpression of PAK5 has been found in several tumors, probably due to its contribution to proliferation, cytoskeleton and anti-apoptosis. Additional regulation mechanisms which are independent of Rho GTPases also indicate that PAK5 functions as a special signal molecule in cellular signaling pathways of tumor progression.
    Expert opinion on therapeutic targets. 05/2014;
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    Ding-Guo Zhang, Jun-Nian Zheng, Dong-Sheng Pei
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    ABSTRACT: MicroRNA-34 (miR-34) is directly regulated by p53, and its potential tumor suppressive roles have been studied extensively. As a p53-induced microRNA, miR-34 functions as a tumor suppressor by playing a role in cell cycle arrest, apoptosis and metabolic regulation. Among these p53/miR-34 associated processes, apoptosis and cell cycle arrest are known as essential for p53/miR-34-mediated tumor suppression. P53-mediated metabolic processes have been shown to play pivotal roles in cancer cell biology. Recent studies have also identified several miR-34 targets involved in p53/miR-34-induced metabolic regulation. However, correlations among these metabolic targets remain to be fully elucidated. In this review, we summarize the current progress in the field of metabolic regulation by the p53/miR-34 axis and propose future directions for the development of metabolic approaches in anticancer therapy.
    Molecular cancer. 05/2014; 13(1):115.
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    ABSTRACT: In order to investigate the relationship between tyrosine phosphorylation of β-catenin and transcriptional activity of β-catenin in Hela and Bcap-37 cells, genistein (a tyrosine kinase inhibitor) was used to inhibit tyrosine phosphorylation in cells. Our results showed the total β-catenin protein levels were mainly equal in Hela, Bcap-37 and HK-2 cells, β-catenin was mainly present in nucleus in Hela and Bcap-37cells, while in HK-2 cell β-catenin was mainly located in cytoplasm. Genistein could inhibit tyrosine phosphorylation of β-catenin and downregulate nuclear β-catenin expression in Hela and Bcap-37 cells. In addition, genistein suppressed Ki-67 promoter activity and Ki-67 protein level, thus promoted cell apoptosis. Furthermore, β-catenin could increase the Ki-67 promoter activity in Hela and Bcap-37 cells. From these findings we conclude that tyrosine phosphorylation of β-catenin can regulate the cellular distribution of β-catenin and affect the transcriptional activity of β-catenin.
    Bioorganic & medicinal chemistry letters 04/2014; · 2.65 Impact Factor
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    ABSTRACT: Primary cutaneous sweat gland carcinoma is a rare neoplasm of malignant sweat gland lesions. It is characterized clinically with non-symptomatic, slow-growing nodules. We report the case of a patient with cutaneous sweat gland carcinoma with local recurrence and metastasis to the lung that was treated with surgical resection therapy and chemotherapy. The initial neoplasm was excised but biopsy was not performed. The tumor then recurred 7 years later, was re-excised, biopsy was performed, and diagnosed as a low-grade hidradenocarcinoma. We presented a very good result of chemotherapy in the treatment of this rare malignant disease. It demonstrates that adjunct chemotherapy is effective to control the condition of malignant sweat-gland carcinomas patient.
    Journal of cancer research and therapeutics. 04/2014; 10(2):390-2.
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    ABSTRACT: Evidence is growing that the GABAB receptor, which belongs to the G protein-coupled receptor (GPCR) superfamily, is involved in tumorigenesis. Recent studies have shown that β-arrestin can serve as a scaffold to recruit signaling protein c-Jun N-terminal knase (JNK) to GPCR. Here we investigated whether β-arrestin recruits JNK to the GABAB receptor and facilitates its activation to affect the growth of cancer cells. Our results showed that β-arrestin expression is decreased in breast cancer cells in comparison with controls. β-arrestin could enhance interactions of the GABABR·β-arrestin·JNK signaling module in MCF-7 and T-47D cells. Further studies revealed that increased expression of β-arrestin enhances the phosphorylation of JNK and induces cancer cells apoptosis. Collectively, these results indicate that β-arrestin promotes JNK mediated apoptosis via a GABABR·β-arrestin·JNK signaling module.
    Asian Pacific journal of cancer prevention: APJCP 01/2014; 15(2):1041-6. · 1.27 Impact Factor
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    ABSTRACT: Peroxisome proliferator-activated receptor gamma (PPAR-γ), a ligand-dependent nuclear transcription factor, has been found to widely exist in tumor tissues and plays an important role in affecting tumor cell growth. In this study, we investigated the effect of PPAR-γ on aspects of the cervical cancer malignant phenotype, such as cell proliferation and apoptosis. Cell growth assay, Western blotting, Annexin V and flow cytometry analysis consistently showed that treatment with troglitazone (TGZ, a PPAR-γ agonist) led to dose-dependent inhibition of cervical cancer cell growth through apoptosis, whereas T0070907 (another PPAR-γ antagonist???) had no effect on Hela cell proliferation and apoptosis. Furthermore, we also detected the protein expression of p53, p21 and Mdm2 to explain the underlying mechanism of PPAR-γ on cellular apoptosis. Our work, finally, demonstrated the existence of the TGZ-PPAR-γ-p53 signaling pathway to be a critical regulator of cell apoptosis. These results suggested that PPAR-γ may be a potential therapeutic target for cervical cancer.
    Asian Pacific journal of cancer prevention: APJCP 01/2014; 15(5):2313-8. · 1.27 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; · 2.91 Impact Factor
  • Shang-Nuan Zhang, Dong-Sheng Pei, Jun-Nian Zheng
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    ABSTRACT: CSN6 is one subunit of the constitutive photomorphogenesis 9 (COP9) signalosome (CSN), which is an evolutionarily conserved multiprotein complex found in plants and animals and originally described as a repressor of light-dependent growth and transcription in Arabidopsis. CSN is homologous to the 19S lid subcomplex of the 26S proteasome, thus it has been postulated to be a regulator of the ubiquitin-proteasome pathway. In mammalian cells, it consists of eight subunits (CSN1-CSN8). Among the CSN subunits, CSN5 and CSN6 are the only two that each contains an MPN (Mpr1p and Pad1p N-terminal) domain. The deneddylating activity of an MPN domain toward cullin-RING ubiquitin ligases (CRL) may coordinate CRL-mediated ubiquitination activity. More and more studies about CSN6 are emerging, and its overexpression is found in many types of cancers. Evidence has shown that CSN6 is a molecule platform between protein degradation and signal transduction. Here, we provide a summary of human CSN6, especially its roles in cancer, hoping that it can lay the groundwork for cancer prevention or therapy.
    Cell Division 11/2013; 8(1):14. · 3.47 Impact Factor
  • Cutis. 11/2013; 92(5):E13-5.
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    ABSTRACT: The PAKs (p21-activated kinases) are highly conserved serine/threonine protein kinases which comprise six mammalian PAKs. PAK5 (p21-activated kinase 5) is the least understood member of PAKs that regulate many intracellular processes when they are stimulated by activated forms of the small GTPases Cdc42 and Rac. PAK5 takes an important part in multiple signal pathways in mammalian cells and controls a variety of cellular functions including cytoskeleton organization, cell motility and apoptosis. The main goal of this review is to describe the structure, mechanisms underlying its activity regulation, its role in apoptosis and the likely directions of further research.
    Bioorganic & medicinal chemistry letters 10/2013; · 2.65 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; · 1.17 Impact Factor
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    ABSTRACT: PAK5 (p21 activated kinase 5) is upregulated in human colorectal carcinoma cells and is a known tumor promoter in carcinogenesis of the colon. Little is known regarding the mechanisms underlying the downstream targets of PAK5, and information concerning its biological significance in glioma is lacking. In this study, we investigated the effects of PAK5 on proliferation, migration, invasion, and apoptosis in human U87 and U251 glioma cells and examined the underlying molecular mechanism. We performed cell growth assays and cell cycle analysis to observe the cell proliferation. Flow cytometry analysis was performed to evaluate apoptosis, and in vitro scratch assays, cell migration assays, and gelatin zymography were performed to examine cell migration. Western blot analysis was performed to examine signal transduction in the cells. We demonstrated that suppression of PAK5 in glioma cells significantly inhibited cell migration and invasion. We also observed that suppression of PAK5 in human glioma cell lines inhibited cell growth because of G1 phase arrest. Additionally, flow cytometry and Western blot analysis indicated that PAK5 could inhibit cell apoptosis. These results suggest that the PAK5-Egr1-MMP2 signaling pathway is involved in tumor progression and may have a potential role in cancer prevention and treatment.
    Brain Tumor Pathology 09/2013; · 1.58 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; · 2.91 Impact Factor
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    ABSTRACT: p21-activated kinases (PAKs) are activated by various extracellular stimuli and, in turn, activate other kinases by phosphorylating them at specific serine/threonine residues or through protein-protein interaction. As a recently identified member of the group B PAK family, the role of PAK5 in cancer is poorly understood. In this study, we investigated the effect of PAK5 on the malignant phenotype, such as proliferation, cell cycle, apoptosis, migration, and invasion. Cell growth assay and cell cycle analysis consistently showed that knockdown of PAK5 could significantly inhibit the proliferation of breast cancer cells. Wound healing assay. migration assay, and invasion assay showed that PAK5 promoted cell migration. Furthermore, in order to elucidate the underlying mechanism of PAK5 on cellular growth and migration, we examined the protein expressions of cyclin D1, p21, early growth response protein 1 (Egr1), and matrix metalloproteinase 2 (MMP2). Our work further reveals the PAK5-Egr1-MMP2 signaling pathway to be a critical regulator of cell migration and invasion. These results suggest that PAK5 may be a potential therapeutic target for breast cancer.
    Tumor Biology 05/2013; · 2.52 Impact Factor
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    ABSTRACT: Malignant melanoma is one of the most lethal and aggressive human malignancies. Suppressed apoptosis and extraordinary invasiveness are the distinctive features that contribute to malignant melanoma. The alkylating agent temozolomide (TMZ) is one of the most effective single chemotherapeutic agents for patients with malignant melanoma, but resistance develops quickly and with high frequency. We constructed a dual-regulated oncolytic adenovirus expressing interleukin 24 (IL-24) gene (Ki67-ZD55-IL-24) by utilizing the Ki67 promoter to replace the native viral promoter of E1A gene. We investigated whether a combination of Ki67-ZD55-IL-24-mediated gene virotherapy and chemotherapy using TMZ produces increased cytotoxicity against human melanoma cells via the induction of apoptosis. Our data indicate that this novel strategy thus holds promising potentials for further developing an effective approach to treat malignant melanoma.
    Tumor Biology 02/2013; · 2.52 Impact Factor
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    Fei-Fei Chen, Guan Jiang, Kerui Xu, Jun-Nian Zheng
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    ABSTRACT: The present review focuses on recent advances in the understanding of the molecular mechnisms by which interferon regulatory factor (IRF)-1 inhibits oncogenesis. IRF-1 is associated with regulation of interferon α and β transcription. In addition, numerous clinical studies have indicated that IRF-1 gene deletion or rearrangement correlates with development of specific forms of human cancer. IRF-1 has been revealed to exhibit marked functional diversity in the regulation of oncogenesis. IRF-1 activates a set of target genes associated with regulation of the cell cycle, apoptosis and the immune response. The role of IRF-1 in the regulation of various types of human tumor has important implications for understanding the susceptibility and progression of cancer. In addition, an improved understanding of the role of IRF-1 in the pathological processes that lead to human malignant diseases may aid development of novel therapeutic strategies.
    Oncology letters 02/2013; 5(2):417-423. · 0.24 Impact Factor
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    ABSTRACT: RGD peptide (Arg-Gly-Asp tripeptide) binds to integrin αVβ(3) and αVβ(5), which is selectively expressed in tumor neovasculature and on the surface of some tumor cells. Some studies showed that coupling the RGD peptides to anticancer drugs yielded compounds with increased efficiency against tumors and lowered toxicity to normal tissues. The melanoma differentiation-associated gene-7/interleukin-24 gene (mda-7/IL-24) is a novel tumor-suppressor/cytokine gene that exhibits potent tumor-suppressive activity without damaging normal cells. To enhance the antitumor effect, we inserted a glycine residue into the wild type (mda-7/IL-24) between (164)Arg and (165)Asp to form a RGD peptide, named RGD-mda-7, then expressed RGD-mda-7 in Escherichia coli. Herein, we describe the expression and purification of RGD-mda-7. We detected the characterizations of immunostimulatory activity, tumor targeting, potent cytopathic effect, and apoptosis inducing exploited by RGD-mda-7 in tumor cells, and also compared these characterizations with wtmda-7/IL-24. The data showed that RGD-mda-7 had more potent tumor targeting and apoptosis-inducing effects than wtmda-7/IL-24.
    Journal of Immunoassay and Immunochemistry 10/2012; 33(4):352-68. · 0.73 Impact Factor
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    ABSTRACT: Combinatorial therapy is the current trend of the development of novel cancer treatments due to the high heterogenous nature of solid tumors. In this study, we investigated the effects of the combined use of a conditionally replicating adenovirus carrying IL-24 (ZD55-IL-24) and radiotherapy on the proliferation and apoptosis of melanoma A375 cells in vitro and in vivo. Compared with either agent used alone, ZD55-IL-24 combined with radiotherapy significantly inhibited cell proliferation, accompanied with increased apoptosis. Radiotherapy did not affect the expression of IL-24 and E1A of ZD55-IL-24-treated cells, but increased the expression of Bax, promoted the activation of caspase-3, while decreasing Bcl-2 levels. Thus, this synergistic effect of ZD55-IL-24 in combination with radiotherapy provides a novel strategy for the development of melanoma therapies, and is a promising approach for further clinical development.
    Molecular oncology 05/2012; 6(4):383-91. · 6.70 Impact Factor

Publication Stats

142 Citations
103.19 Total Impact Points

Institutions

  • 2005–2014
    • Xuzhou Medical College
      • • Laboratory of Biological Cancer Therapy
      • • Research Center for Biochemistry and Molecular Biology
      Suchow, Jiangsu Sheng, China
  • 2012
    • Nanjing Medical University
      Nan-ching, Jiangsu Sheng, China
  • 2011
    • Shenzhen Center for Disease Control and Prevention
      Bao'an, Guangdong, China