Hepatitis B virus X protein inhibits tumor suppressor miR-205 through inducing hypermethylation of miR-205 promoter to enhance carcinogenesis.

Abstract:

:The infection of hepatitis B virus (HBV) is closely associated with the development of hepatocellular carcinoma (HCC), in which HBV X protein (HBx) plays crucial roles. MicroRNAs are involved in diverse biologic functions and in carcinogenesis by regulating gene expression. In the present study, we aim to investigate the underlying mechanism by which HBx enhances hepatocarcinogenesis. We found that miR-205 was downregulated in 33 clinical HCC tissues in comparison with adjacent noncancerous hepatic tissues. The expression levels of miR-205 were inversely correlated with those of HBx in abovementioned tissues. Then, we demonstrated that HBx was able to suppress miR-205 expression in hepatoma and liver cells. We validated that miR-205 directly targeted HBx mRNA. Ectopic expression of miR-205 downregulated HBx, whereas depletion of endogenous miR-205 upregulated HBx in hepatoma cells. Notably, our data revealed that HBx downregulated miR-205 through inducing hypermethylation of miR-205 promoter in the cells. In terms of function, the forced miR-205 expression remarkably inhibited the HBx-enhanced proliferation of hepatoma cells in vitro and in vivo, suggesting that miR-205 is a potential tumor-suppressive gene in HCC. HBx-transgenic mice showed that miR-205 was downregulated in the liver. Importantly, HBx was able to abrogate the effect of miR-205 on tumor suppression in carcinogenesis. Therefore, we conclude that HBx is able to inhibit tumor suppressor miR-205 to enhance hepatocarcinogenesis through inducing hypermethylation of miR-205 promoter during their interaction. Therapeutically, miR-205 may be useful in the treatment of HCC.

journal_name

Neoplasia

authors

Zhang T,Zhang J,Cui M,Liu F,You X,Du Y,Gao Y,Zhang S,Lu Z,Ye L,Zhang X

doi

10.1593/neo.131362

subject

Has Abstract

pub_date

2013-11-01 00:00:00

pages

1282-91

issue

11

eissn

1522-8002

issn

1476-5586

journal_volume

15

pub_type

杂志文章
  • Insulin-like growth factor-1 inscribes a gene expression profile for angiogenic factors and cancer progression in breast epithelial cells.

    abstract::Activation of the insulin-like growth factor-1 receptor (IGF-1R) by IGF-1 is associated with the risk and progression of many types of cancer, although despite this it remains unclear how activated IGF-1R contributes to cancer progression. In this study, gene expression changes elicited by IGF-1 were profiled in breas...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1038/sj.neo.7900229

    authors: Oh JS,Kucab JE,Bushel PR,Martin K,Bennett L,Collins J,DiAugustine RP,Barrett JC,Afshari CA,Dunn SE

    更新日期:2002-05-01 00:00:00

  • Deleterious c-Cbl Exon Skipping Contributes to Human Glioma.

    abstract::c-Cbl, a RING-type ubiquitin E3 ligase, downregulates various receptor tyrosine kinases (e.g., epidermal growth factor receptor (EGFR)), leading to inhibition of cell proliferation. Moreover, patients with myeloid neoplasm frequently harbor c-Cbl mutations, implicating the role of c-Cbl as a tumor suppressor. Recently...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/j.neo.2015.06.003

    authors: Seong MW,Ka SH,Park JH,Park JH,Yoo HM,Yang SW,Park JM,Park D,Lee ST,Seol JH,Chung CH

    更新日期:2015-06-01 00:00:00

  • Imbalance between genomic gain and loss identifies high-risk neuroblastoma patients with worse outcomes.

    abstract::Survival in high-risk neuroblastoma (HR-NB) patients remains poor despite multimodal treatment. We aimed to identify HR-NB patients with worse outcomes by analyzing the genomic instability derived from segmental chromosomal aberrations. We calculated 3 genomic instability indexes for primary tumor SNP array profiles f...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/j.neo.2020.11.001

    authors: Fernández-Blanco B,Berbegall AP,Martin-Vañó S,Castel V,Navarro S,Noguera R

    更新日期:2021-01-01 00:00:00

  • An alternate splicing variant of the human telomerase catalytic subunit inhibits telomerase activity.

    abstract::Telomerase, a cellular reverse transcriptase, adds telomeric repeats to chromosome ends. In normal human somatic cells, telomerase is repressed and telomeres progressively shorten, leading to proliferative senescence. Introduction of the telomerase (hTERT) cDNA is sufficient to produce telomerase activity and immortal...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1038/sj.neo.7900113

    authors: Yi X,White DM,Aisner DL,Baur JA,Wright WE,Shay JW

    更新日期:2000-09-01 00:00:00

  • Paradoxically augmented anti-tumorigenic action of proton pump inhibitor and GastrininAPCMin/+ intestinal polyposis model.

    abstract::Though long-term administration of proton pump inhibitor (PPI) imposed the risk of gastrointestinal track tumorigenesis by accompanied hypergastrinemia, no overt increases of colon cancer risk were witnessed after a long-term cohort study. Our recent investigation revealed that PPI prevented colitis-associated carcino...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.131510

    authors: Han YM,Hahm KB,Park JM,Hong SP,Kim EH

    更新日期:2014-01-01 00:00:00

  • Vascular differences detected by MRI for metastatic versus nonmetastatic breast and prostate cancer xenografts.

    abstract::Several studies have linked vascular density, identified in histologic sections, to "metastatic risk." Functional information of the vasculature, not readily available from histologic sections, can be obtained with contrast-enhanced MRI to exploit for therapy or metastasis prevention. Our aims were to determine if hum...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1038/sj.neo.7900129

    authors: Bhujwalla ZM,Artemov D,Natarajan K,Ackerstaff E,Solaiyappan M

    更新日期:2001-03-01 00:00:00

  • Behavior of endogenous tumor-associated macrophages assessed in vivo using a functionalized nanoparticle.

    abstract::Tumor-associated macrophages (TAMs) invade the tumor stroma in many cancers, yet their role is incompletely understood. To visualize and better understand these critical cells in tumor progression, we screened a portfolio of rationally selected, injectable agents to image endogenous TAMs ubiquitously in three differen...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.09356

    authors: Leimgruber A,Berger C,Cortez-Retamozo V,Etzrodt M,Newton AP,Waterman P,Figueiredo JL,Kohler RH,Elpek N,Mempel TR,Swirski FK,Nahrendorf M,Weissleder R,Pittet MJ

    更新日期:2009-05-01 00:00:00

  • Nothing But NET: A Review of Neuroendocrine Tumors and Carcinomas.

    abstract::This review covers the diverse topic of neuroendocrine neoplasms (NENs), a relatively rare and heterogeneous tumor type, comprising ~2% of all malignancies, with a prevalence of <200,000 in the United States, which makes it an orphan disease (Basu et al., 2010).1 For functional purposes, NENs are divided into two grou...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章,评审

    doi:10.1016/j.neo.2017.09.002

    authors: Oronsky B,Ma PC,Morgensztern D,Carter CA

    更新日期:2017-12-01 00:00:00

  • Isolation of a novel human gene, MARKL1, homologous to MARK3 and its involvement in hepatocellular carcinogenesis.

    abstract::Activation of the Wnt-signaling pathway is known to play a crucial role in carcinogenesis of various human organs including the colon, liver, prostate, and endometrium. To investigate the mechanisms underlying hepatocellular carcinogenesis, we attempted to identify genes regulated by beta-catenin/Tcf complex in a huma...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1038/sj.neo.7900132

    authors: Kato T,Satoh S,Okabe H,Kitahara O,Ono K,Kihara C,Tanaka T,Tsunoda T,Yamaoka Y,Nakamura Y,Furukawa Y

    更新日期:2001-01-01 00:00:00

  • A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma.

    abstract::Melanomas are highly radioresistant tumors, mainly due to efficient DNA double-strand break (DSB) repair. Dbait (which stands for DNA strand break bait) molecules mimic DSBs and trap DNA repair proteins, thereby inhibiting repair of DNA damage induced by radiation therapy (RT). First, the cytotoxic efficacy of Dbait i...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/j.neo.2014.08.008

    authors: Biau J,Devun F,Jdey W,Kotula E,Quanz M,Chautard E,Sayarath M,Sun JS,Verrelle P,Dutreix M

    更新日期:2014-10-23 00:00:00

  • Neutralization of tumor necrosis factor bioactivity ameliorates urethane-induced pulmonary oncogenesis in mice.

    abstract::Tumor necrosis factor (TNF) has been implicated in inflammation-associated tumor progression. Although multiple reports identified a role for TNF signaling in established cancers, few studies have assessed the impact of TNF blockade on early tumor formation promotion. We aimed at exploring the effects of TNF neutraliz...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.111224

    authors: Karabela SP,Kairi CA,Magkouta S,Psallidas I,Moschos C,Stathopoulos I,Zakynthinos SG,Roussos C,Kalomenidis I,Stathopoulos GT

    更新日期:2011-12-01 00:00:00

  • Adenomatous polyposis coli-mediated accumulation of abasic DNA lesions lead to cigarette smoke condensate-induced neoplastic transformation of normal breast epithelial cells.

    abstract::Adenomatous polyposis coli (APC) is a multifunctional protein having diverse cellular functions including cell migration, cell-cell adhesion, cell cycle control, chromosomal segregation, and apoptosis. Recently, we found a new role of APC in base excision repair (BER) and showed that it interacts with DNA polymerase β...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.13176

    authors: Jaiswal AS,Panda H,Pampo CA,Siemann DW,Gairola CG,Hromas R,Narayan S

    更新日期:2013-04-01 00:00:00

  • A Novel Method for Quantifying Total Thoracic Tumor Burden in Mice.

    abstract::Mouse models are powerful tools to study lung cancer initiation and progression in vivo and have contributed significantly to recent advances in therapy. Using micro-computed tomography to monitor and study parenchymal and extra-parenchymal metastases in existing murine models of lung cancer is challenging owing to a ...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/j.neo.2018.08.003

    authors: Viswanath P,Peng S,Singh R,Kingsley C,Balter PA,Johnson FM

    更新日期:2018-10-01 00:00:00

  • Chemotherapy-induced and/or radiation therapy-induced oral mucositis--complicating the treatment of cancer.

    abstract::The term mucositis is coined to describe the adverse effects of radiation and chemotherapy treatments. Mucositis is one of the most common adverse reactions encountered in radiation therapy for head and neck cancers, as well as in chemotherapy, in particular with drugs affecting DNA synthesis (S-phase-specific agents ...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章,评审

    doi:10.1593/neo.04169

    authors: Naidu MU,Ramana GV,Rani PU,Mohan IK,Suman A,Roy P

    更新日期:2004-09-01 00:00:00

  • N-myc downstream regulated gene 1 (NDRG1) is fused to ERG in prostate cancer.

    abstract::A step toward the molecular classification of prostate cancer was the discovery of recurrent erythroblast transformation-specific rearrangements, most commonly fusing the androgen-regulated TMPRSS2 promoter to ERG. The TMPRSS2-ERG fusion is observed in around 90% of tumors that overexpress the oncogene ERG. The goal o...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.09572

    authors: Pflueger D,Rickman DS,Sboner A,Perner S,LaFargue CJ,Svensson MA,Moss BJ,Kitabayashi N,Pan Y,de la Taille A,Kuefer R,Tewari AK,Demichelis F,Chee MS,Gerstein MB,Rubin MA

    更新日期:2009-08-01 00:00:00

  • Colorectal cancer "methylator phenotype": fact or artifact?

    abstract::It has been proposed that human colorectal tumors can be classified into two groups: one in which methylation is rare, and another with methylation of several loci associated with a "CpG island methylated phenotype (CIMP)," characterized by preferential proximal location in the colon, but otherwise poorly defined. The...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.04502

    authors: Anacleto C,Leopoldino AM,Rossi B,Soares FA,Lopes A,Rocha JC,Caballero O,Camargo AA,Simpson AJ,Pena SD

    更新日期:2005-04-01 00:00:00

  • Hyaluronic acid-paclitaxel: antitumor efficacy against CD44(+) human ovarian carcinoma xenografts.

    abstract::Numerous human tumor types, including ovarian cancer, display a significant expression of the CD44 family of cell surface proteoglycans. To develop tumor-targeted drugs, we have initially evaluated whether the CD44 ligand hyaluronic acid (HA) could serve as a backbone for paclitaxel (TXL) prodrugs. HA-TXL was prepared...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.07229

    authors: Auzenne E,Ghosh SC,Khodadadian M,Rivera B,Farquhar D,Price RE,Ravoori M,Kundra V,Freedman RS,Klostergaard J

    更新日期:2007-06-01 00:00:00

  • Synthesis, Characterization, and In Vitro and In Vivo Evaluations of 4-(N)-Docosahexaenoyl 2', 2'-Difluorodeoxycytidine with Potent and Broad-Spectrum Antitumor Activity.

    abstract::In this study, a new compound, 4-(N)-docosahexaenoyl 2', 2'-difluorodeoxycytidine (DHA-dFdC), was synthesized and characterized. Its antitumor activity was evaluated in cell culture and in mouse models of pancreatic cancer. DHA-dFdC is a poorly soluble, pale yellow waxy solid, with a molecular mass of 573.3Da and a me...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/j.neo.2015.11.012

    authors: Naguib YW,Lansakara-P D,Lashinger LM,Rodriguez BL,Valdes S,Niu M,Aldayel AM,Peng L,Hursting SD,Cui Z

    更新日期:2016-01-01 00:00:00

  • Noninvasive Bioluminescence Imaging of AKT Kinase Activity in Subcutaneous and Orthotopic NSCLC Xenografts: Correlation of AKT Activity with Tumor Growth Kinetics.

    abstract::Aberrant signaling through the AKT kinase mediates oncogenic phenotypes including cell proliferation, survival, and therapeutic resistance. Here, we utilize a bioluminescence reporter for AKT kinase activity (BAR) to noninvasively assess the therapeutic efficacy of the EGFR inhibitor erlotinib in KRAS-mutated lung can...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/j.neo.2017.02.005

    authors: Suchowski K,Pöschinger T,Rehemtulla A,Stürzl M,Scheuer W

    更新日期:2017-04-01 00:00:00

  • Lysophosphatidic Acid Up-Regulates Hexokinase II and Glycolysis to Promote Proliferation of Ovarian Cancer Cells.

    abstract::Lysophosphatidic acid (LPA), a blood-borne lipid mediator, is present in elevated concentrations in ascites of ovarian cancer patients and other malignant effusions. LPA is a potent mitogen in cancer cells. The mechanism linking LPA signal to cancer cell proliferation is not well understood. Little is known about whet...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/j.neo.2015.09.003

    authors: Mukherjee A,Ma Y,Yuan F,Gong Y,Fang Z,Mohamed EM,Berrios E,Shao H,Fang X

    更新日期:2015-09-01 00:00:00

  • Accelerated degradation of caspase-8 protein correlates with TRAIL resistance in a DLD1 human colon cancer cell line.

    abstract::The tumor-selective cytotoxic effect of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) makes TRAIL an attractive candidate as an anticancer agent. However, resistance to TRAIL poses a challenge in anticancer therapy with TRAIL. Therefore, characterizing the mechanisms of resistance and developing stra...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.04688

    authors: Zhang L,Zhu H,Teraishi F,Davis JJ,Guo W,Fan Z,Fang B

    更新日期:2005-06-01 00:00:00

  • Polyploidy Formation in Doxorubicin-Treated Cancer Cells Can Favor Escape from Senescence.

    abstract::Cancer cells can undergo stress-induced premature senescence, which is considered to be a desirable outcome of anticancer treatment. However, the escape from senescence and cancer cell repopulation give rise to some doubts concerning the effectiveness of the senescence-induced anticancer therapy. Similarly, it is post...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/j.neo.2015.11.008

    authors: Mosieniak G,Sliwinska MA,Alster O,Strzeszewska A,Sunderland P,Piechota M,Was H,Sikora E

    更新日期:2015-12-01 00:00:00

  • Gastrin-releasing peptide receptor mediates activation of the epidermal growth factor receptor in lung cancer cells.

    abstract::Gastrin-releasing peptide receptor (GRPR) and the epidermal growth factor receptor (EGFR) are expressed in several cancers including non-small cell lung cancer (NSCLC). Here we demonstrate the activation of EGFR by the GRPR ligand, gastrin-releasing peptide (GRP), in NSCLC cells. GRP induced rapid activation of p44/42...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.04454

    authors: Thomas SM,Grandis JR,Wentzel AL,Gooding WE,Lui VW,Siegfried JM

    更新日期:2005-04-01 00:00:00

  • Inhibitors of GLUT/SLC2A Enhance the Action of BCNU and Temozolomide against High-Grade Gliomas.

    abstract::Glucose transport across glioblastoma membranes plays a crucial role in maintaining the enhanced glycolysis typical of high-grade gliomas and glioblastoma. We tested the ability of two inhibitors of the glucose transporters GLUT/SLC2A superfamily, indinavir (IDV) and ritonavir (RTV), and of one inhibitor of the Na/glu...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/j.neo.2017.02.009

    authors: Azzalin A,Nato G,Parmigiani E,Garello F,Buffo A,Magrassi L

    更新日期:2017-04-01 00:00:00

  • Chromosomal localization of DNA amplifications in neuroblastoma tumors using cDNA microarray comparative genomic hybridization.

    abstract::Conventional comparative genomic hybridization (CGH) profiling of neuroblastomas has identified many genomic aberrations, although the limited resolution has precluded a precise localization of sequences of interest within amplicons. To map high copy number genomic gains in clinically matched stage IV neuroblastomas, ...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/s1476-5586(03)80017-9

    authors: Beheshti B,Braude I,Marrano P,Thorner P,Zielenska M,Squire JA

    更新日期:2003-01-01 00:00:00

  • Radiocurability is associated with interstitial fluid pressure in human tumor xenografts.

    abstract::Interstitial fluid pressure (IFP) has been shown to be an independent prognostic parameter for disease-free survival in cervical carcinoma patients treated with radiation therapy. However, the underlying mechanisms are not fully understood. The main aims of this study were to investigate whether tumor radiocurability ...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.91152

    authors: Rofstad EK,Gaustad JV,Brurberg KG,Mathiesen B,Galappathi K,Simonsen TG

    更新日期:2009-11-01 00:00:00

  • Stromal PDGFR-α Activation Enhances Matrix Stiffness, Impedes Mammary Ductal Development, and Accelerates Tumor Growth.

    abstract::The extracellular matrix (ECM) is critical for mammary ductal development and differentiation, but how mammary fibroblasts regulate ECM remodeling remains to be elucidated. Herein, we used a mouse genetic model to activate platelet derived growth factor receptor-alpha (PDGFRα) specifically in the stroma. Hyperactivati...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/j.neo.2017.04.004

    authors: Hammer AM,Sizemore GM,Shukla VC,Avendano A,Sizemore ST,Chang JJ,Kladney RD,Cuitiño MC,Thies KA,Verfurth Q,Chakravarti A,Yee LD,Leone G,Song JW,Ghadiali SN,Ostrowski MC

    更新日期:2017-06-01 00:00:00

  • Changes in water mobility measured by diffusion MRI predict response of metastatic breast cancer to chemotherapy.

    abstract::The goal of oncology is the individualization of patient care to optimize therapeutic responses and minimize toxicities. Achieving this will require noninvasive, quantifiable, and early markers of tumor response. Preclinical data from xenografted tumors using a variety of antitumor therapies have shown that magnetic r...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.03343

    authors: Theilmann RJ,Borders R,Trouard TP,Xia G,Outwater E,Ranger-Moore J,Gillies RJ,Stopeck A

    更新日期:2004-11-01 00:00:00

  • Merlin-deficient human tumors show loss of contact inhibition and activation of Wnt/β-catenin signaling linked to the PDGFR/Src and Rac/PAK pathways.

    abstract::Neurofibromatosis type 2 (NF2) is an inherited predisposition cancer syndrome characterized by the development of multiple benign tumors in the nervous system including schwannomas, meningiomas, and ependymomas. Using a disease model comprising primary human schwannoma cells, we previously demonstrated that adherens j...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.111060

    authors: Zhou L,Ercolano E,Ammoun S,Schmid MC,Barczyk MA,Hanemann CO

    更新日期:2011-12-01 00:00:00

  • PIAS1-FAK Interaction Promotes the Survival and Progression of Non-Small Cell Lung Cancer.

    abstract::The sequence of genomic alterations acquired by cancer cells during tumor progression and metastasis is poorly understood. Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that integrates cytoskeleton remodeling, mitogenic signaling and cell survival. FAK has previously been reported to undergo nuclear lo...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/j.neo.2016.03.003

    authors: Constanzo JD,Tang KJ,Rindhe S,Melegari M,Liu H,Tang X,Rodriguez-Canales J,Wistuba I,Scaglioni PP

    更新日期:2016-05-01 00:00:00