Hailong Wu

University of Illinois Springfield, Спрингфилд, Florida, United States

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Publications (10)65.9 Total impact

  • No preview · Article · Jan 2011 · Cancer Research
  • Hailong Wu · Yin-Yuan Mo
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    ABSTRACT: As small non-coding regulatory RNAs, microRNAs are capable of silencing gene expression by translational repression or mRNA degradation. Accumulating evidence indicates that deregulation of microRNAs is often associated with human malignancies and suggests a causal role of microRNAs in neoplasia, presumably because microRNAs can function as oncogenes or tumor suppressors. Among them, miR-205 is significantly underexpressed in breast tumors compared with matched normal breast tissue although miR-205 has been shown to be upregulated in some other type of tumors. Furthermore, breast cancer cell lines, including MCF-7 and MDA-MB-231, express a lower level of miR-205 than the non-malignant MCF-10A cells. Ectopic expression of miR-205 significantly inhibits cell proliferation and anchorage-independent growth as well as cell invasion. These findings establish the tumor suppressive role of miR-205, which is probably through direct targeting of oncogenes such as ErbB3 and Zeb1. Therefore, miR-205 may serve as a unique therapeutic target for breast cancer.
    No preview · Article · Oct 2009 · Expert Opinion on Therapeutic Targets
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    ABSTRACT: In addition to transactivation of interleukin-4 (IL-4), cellular muscular aponeurotic fibrosarcoma (c-Maf) enhances CD4 cell apoptosis by limiting Bcl-2 expression. The CD8 cells also express c-Maf and peripheral CD8 cell numbers are reduced in c-Maf transgenic mice, suggesting that c-Maf may influence CD8 cell survival in a manner similar to CD4 cells. Here we confirm that, similar to CD4 cells, c-Maf enhances CD8 cell susceptibility to apoptosis induced by multiple stimuli, independent of IL-4. However, unlike CD4 cells, c-Maf enhancement of apoptosis is independent of Bcl-2, suggesting that c-Maf uses other mechanisms to regulate CD8 cell apoptosis. Real-time reverse transcription-polymerase chain reaction reveals that the pro-apoptotic gene Caspase 6 is upregulated in c-Maf transgenic CD8 cells, suggesting that Caspase 6 is a novel c-Maf target gene. Luciferase reporter assays and site-directed mutagenesis reveal a functional c-Maf recognition element (MARE) within the first intron of Caspase 6. Binding of c-Maf to the MARE site is detectable by chromatin immunoprecipitation using non-transgenic T-cell lysates, so c-Maf can interact with the Caspase 6 MARE site in normal T cells. Furthermore, caspase 6 activity is increased among CD8 cells from c-Maf transgenic mice following T-cell receptor engagement. As expected, activity of the downstream caspases 3 and 7 is also increased. Consistent with the ability of caspase 6 to participate in positive feedback loops, cytochrome c release and caspase 8 activation are also increased. Together these results indicated that c-Maf increases CD8 cell sensitivity to apoptotic stimuli, at least in part, by direct transactivation of Caspase 6, providing increased substrate for Caspase 6-dependent apoptosis pathways.
    Preview · Article · Jul 2009 · Immunology
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    ABSTRACT: The tumor suppressor p53 negatively regulates a number of genes, including the proto-oncogene c-Myc, in addition to activating many other genes. One mechanism of the p53-mediated c-Myc repression may involve transcriptional regulation. However, it is not clear whether microRNAs (miRNAs) play a role in the p53-mediated posttranscriptional regulation of c-Myc. In this study, we show that a putative tumor suppressor, miR-145, is expressed through the phosphoinositide-3 kinase (PI-3K)/Akt and p53 pathways. Importantly, p53 transcriptionally induces the expression of miR-145 by interacting with a potential p53 response element (p53RE) in the miR-145 promoter. We further show that c-Myc is a direct target for miR-145. Although miR-145 silences the expression of c-Myc, anti-miR-145 enhances its expression. This specific silencing of c-Myc by miR-145 accounts at least in part for the miR-145-mediated inhibition of tumor cell growth both in vitro and in vivo. Finally, the blockade of miR-145 by anti-miR-145 is able to reverse the p53-mediated c-Myc repression. Together, these results define the role of miR-145 in the posttranscriptional regulation of c-Myc by p53 and suggest that, as a new member of the p53 regulatory network, miR-145 provides a direct link between p53 and c-Myc in this gene regulatory network.
    Full-text · Article · Mar 2009 · Proceedings of the National Academy of Sciences
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    Hailong Wu · Shoumin Zhu · Yin-Yuan Mo
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    ABSTRACT: MicroRNAs (miRNAs) are endogenous, small, non-coding RNAs, which are capable of silencing gene expression at the post-transcriptional level. In this study, we report that miR-205 is significantly underexpressed in breast tumor compared to the matched normal breast tissue. Similarly, breast cancer cell lines, including MCF-7 and MDA-MB-231, express a lower level miR-205 than the non-malignant MCF-10A cells. Of interest, ectopic expression of miR-205 significantly inhibits cell proliferation and anchorage independent growth, as well as cell invasion. Furthermore, miR-205 was shown to suppress lung metastasis in an animal model. Finally, western blot combined with the luciferase reporter assays demonstrate that ErbB3 and vascular endothelial growth factor A (VEGF-A) are direct targets for miR-205, and this miR-205-mediated suppression is likely through the direct interaction with the putative miR-205 binding site in the 3'-untranslated region (3'-UTR) of ErbB3 and VEGF-A. Together, these results suggest that miR-205 is a tumor suppressor in breast cancer.
    Preview · Article · Mar 2009 · Cell Research
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    ABSTRACT: MicroRNAs (miRNAs) are a class of naturally occurring small non-coding RNAs that target protein-coding mRNAs at the post-transcriptional level. Our previous studies suggest that mir-21 functions as an oncogene and has a role in tumorigenesis, in part through regulation of the tumor suppressor gene tropomyosin 1 (TPM1). Given that TPM1 has been implicated in cell migration, in this study we further investigated the role of mir-21 in cell invasion and tumor metastasis. We found that suppression of mir-21 in metastatic breast cancer MDA-MB-231 cells significantly reduced invasion and lung metastasis. Consistent with this, ectopic expression of TPM1 remarkably reduced cell invasion. Furthermore, we identified two additional direct mir-21 targets, programmed cell death 4 (PDCD4) and maspin, both of which have been implicated in invasion and metastasis. Like TPM1, PDCD4 and maspin also reduced invasiveness of MDA-MB-231 cells. Finally, the expression of PDCD4 and maspin inversely correlated with mir-21 expression in human breast tumor specimens, indicating the potential regulation of PDCD4 and maspin by mir-21 in these tumors. Taken together, the results suggest that, as an oncogenic miRNA, mir-21 has a role not only in tumor growth but also in invasion and tumor metastasis by targeting multiple tumor/metastasis suppressor genes. Therefore, suppression of mir-21 may provide a novel approach for the treatment of advanced cancers.
    Preview · Article · Apr 2008 · Cell Research
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    Shuomin Zhu · Min-Liang Si · Hailong Wu · Yin-Yuan Mo
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    ABSTRACT: MicroRNAs are small noncoding RNA molecules that control expression of target genes. Our previous studies show that mir-21 is overexpressed in tumor tissues compared with the matched normal tissues. Moreover, suppression of mir-21 by antisense oligonucleotides inhibits tumor cell growth both in vitro and in vivo. However, it remains largely unclear as to how mir-21 affects tumor growth, because our understanding of mir-21 targets is limited. In this study, we performed two-dimensional differentiation in-gel electrophoresis of tumors treated with anti-mir-21 and identified the tumor suppressor tropomyosin 1 (TPM1) as a potential mir-21 target. In agreement with this, there is a putative mir-21 binding site at the 3′-untranslated region (3′-UTR) of TPM1 variants V1 and V5. Thus, we cloned the 3′-UTR of TPM1 into a luciferase reporter and found that although mir-21 down-regulated the luciferase activity, anti-mir-21 up-regulated it. Moreover, deletion of the mir-21 binding site abolished the effect of mir-21 on the luciferase activity, suggesting that this mir-21 binding site is critical. Western blot with the cloned TPM1-V1 plus the 3′-UTR indicated that TPM1 protein level was also regulated by mir-21, whereas real-time quantitative reverse transcription-PCR revealed no difference at the mRNA level, suggesting translational regulation. Finally, overexpression of TPM1 in breast cancer MCF-7 cells suppressed anchorage-independent growth. Thus, down-regulation of TPM1 by mir-21 may explain, at least in part, why suppression of mir-21 can inhibit tumor growth, further supporting the notion that mir-21 functions as an oncogene.
    Preview · Article · Jun 2007 · Journal of Biological Chemistry
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    ABSTRACT: Breast cancer is one of the most debilitating human carcinomas with second highest mortality rate after lung cancer in women. Recent advancement in genetic and biochemical analyses has deciphered the molecular pathways involved in breast cancer development. Wnt signal has long been established to play a critical role in normal development as well as in tumorigenesis. In this review, we summarize the role of Wnt signal in the development of mammary carcinoma, the molecular mechanism via which Wnt signal exerts its malignant potential and various nodal points in the Wnt cascade that can be targeted for drug development and cancer treatment.
    Preview · Article · Feb 2007 · Frontiers in Bioscience
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    Hailong Wu · Anh Dinh · Yin-Yuan Mo
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    ABSTRACT: Suppression of gene expression by small interfering RNA (siRNA) has proved to be a gene-specific and cost effective alternative to other gene suppression technologies. Short hairpin RNAs (shRNAs) generated from the vector-based expression are believed to be processed into functional siRNAs in vivo, leading to gene silencing. Since an shRNA library carries a large pool of potential siRNAs, such a library makes it possible to knock down gene expression at the genome wide scale. Although much of research has been focused on generating shRNA libraries from either individually made gene specific sequences or cDNA libraries, there is no report on constructing randomized shRNA libraries, which could provide a good alternative to these existing libraries. We have developed a method of constructing shRNAs from randomized oligonucleotides. Through this method, one can generate a partially or fully randomized shRNA library for various functional analyses. We validated this procedure by constructing a p53-specific shRNA. Western blot revealed that the p53-shRNA successfully suppressed expression of the endogenous p53 in MCF-7 cells. We then made a partially randomized shRNA library. Sequencing of 15 randomly picked cloned confirmed the randomness of the library. Therefore, the library can be used for various functional assays, such as target validation when a suitable screening or selection method is available.
    Preview · Article · Feb 2007 · Biological Procedures Online
  • Zhaohui Lu · Hailong Wu · Yin-Yuan Mo
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    ABSTRACT: Posttranslational modifications mediated by ubiquitin-like proteins have been implicated in regulating a variety of cellular pathways. Although small ubiquitin-like modifier (SUMO) is a new member of this family, it has caught a great deal of attention recently because of its novel and distinguished functions. Sumoylation is a multiple-step process, involving maturation, activation, conjugation and ligation. Ubc9 is an E2 conjugating enzyme essential for sumoylation. We have previously shown that suppression of sumoylation by a dominant negative Ubc9 mutant (Ubc9-DN) in the estrogen receptor (ER) positive MCF-7 cells is associated with alterations of tumor cell's response to anticancer drugs as well as tumor growth in a xenograft mouse carcinoma model. To dissect the underlying mechanism of Ubc9-associated alterations of drug responsiveness and tumor growth, we profiled gene expression for the cells expressing wild type Ubc9 (Ubc9-WT) and Ubc9-DN. We found that several tumorigenesis-related genes were downregulated in the Ubc9-DN cells. Within this group, we found that over 10 genes are known to be regulated by ER. Experiments using the estrogen response element fused to the luciferase reporter showed that the basal level of luciferase activity was significantly reduced in the Ubc9-DN cells when compared to the vector alone or the Ubc9-WT cells. Furthermore, we found that both the stability and the subcellular localization of steroid hormone receptor coactivator-1 (SRC-1) were altered in the Ubc9-DN cells. Together, these results suggest that Ubc9 might regulate bcl-2 expression through the ER signaling pathway, which ultimately contributes to the alterations of drug responsiveness and tumor growth.
    No preview · Article · Jul 2006 · Experimental Cell Research

Publication Stats

2k Citations
65.90 Total Impact Points


  • 2009
    • University of Illinois Springfield
      Спрингфилд, Florida, United States
  • 2006-2009
    • Southern Illinois University School of Medicine
      • Department of Medical Microbiology, Immunology and Cell Biology
      Springfield, Illinois, United States
  • 2007
    • Southern Illinois University Carbondale
      • Department of Medical Microbiology, Immunology and Cell Biology
      Illinois, United States