miR-93-directed downregulation of DAB2 defines a novel oncogenic pathway in lung cancer.

Abstract:

:The disabled homolog 2 (DAB2) gene was recently identified as a tumor suppressor gene with its expression downregulated in multiple cancer types. The role of DAB2 in lung tumorigenesis, however, is not fully characterized, and the mechanisms of DAB2 dysregulation in lung cancer are not defined. Here we show that low DAB2 levels in lung tumor specimens are significantly correlated with poor patient survival, and that DAB2 overexpression significantly inhibits cell growth in cultured lung cancer cells, indicating its potent tumor suppressor function. We next identify that microRNA miR-93 functions as a potent repressor of DAB2 expression by directly targeting the 3'UTR of the DAB2 mRNA. Using in vitro and in vivo approaches, we demonstrate that miR-93 overexpression has an important role in promoting lung cancer cell growth, and that its oncogenic function is primarily mediated by downregulating DAB2 expression. Our clinical investigations further indicate that high tumor levels of miR-93 are correlated with poor survival of lung cancer patients. The correlations of both low DAB2 and high miR-93 expression levels with poor patient survival strongly support the critical role of the miR-93/DAB2 pathway in determining lung cancer progression.

journal_name

Oncogene

journal_title

Oncogene

authors

Du L,Zhao Z,Ma X,Hsiao TH,Chen Y,Young E,Suraokar M,Wistuba I,Minna JD,Pertsemlidis A

doi

10.1038/onc.2013.381

subject

Has Abstract

pub_date

2014-08-21 00:00:00

pages

4307-15

issue

34

eissn

0950-9232

issn

1476-5594

pii

onc2013381

journal_volume

33

pub_type

杂志文章

相关文献

ONCOGENE文献大全
  • The autophagic paradox in cancer therapy.

    abstract::Autophagy, hallmarked by the formation of double-membrane bound organelles known as autophagosomes, is a lysosome-dependent pathway for protein degradation. The role of autophagy in carcinogenesis is context dependent. As a tumor-suppressing mechanism in early-stage carcinogenesis, autophagy inhibits inflammation and ...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:10.1038/onc.2011.295

    authors: Wu WK,Coffelt SB,Cho CH,Wang XJ,Lee CW,Chan FK,Yu J,Sung JJ

    更新日期:2012-02-23 00:00:00

  • Transcriptional upregulation of SPARC, in response to c-Jun overexpression, contributes to increased motility and invasion of MCF7 breast cancer cells.

    abstract::Overexpression of the c-Jun proto-oncogene in MCF7 breast cancer cells results in a variety of phenotype changes related to malignant progression including increased motility and invasion. Concurrent with these phenotypic effects are changes in the expression of multiple gene targets. We previously demonstrated that e...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1205857

    authors: Briggs J,Chamboredon S,Castellazzi M,Kerry JA,Bos TJ

    更新日期:2002-10-10 00:00:00

  • N-Myc overexpression leads to decreased beta1 integrin expression and increased apoptosis in human neuroblastoma cells.

    abstract::Neuroblastoma is a childhood tumor thought to arise through improper differentiation of neural crest cells. Increased N-Myc expression in neuroblastoma indicates highly malignant disease and poor patient prognosis. N-myc enhances cell growth, insulin-like growth factor type I receptor (IGF-IR) expression, and tumorige...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1206362

    authors: van Golen CM,Soules ME,Grauman AR,Feldman EL

    更新日期:2003-05-01 00:00:00

  • Functional capabilities of molecular network components controlling the mammalian G1/S cell cycle phase transition.

    abstract::The molecular interactions implicated in the mammalian G1/S cell cycle phase transition comprise a highly nonlinear network which can produce seemingly paradoxical results and make intuitive interpretations unreliable. A new approach to this problem is presented, consisting of (1) a convention of unambiguous reaction ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1201608

    authors: Kohn KW

    更新日期:1998-02-26 00:00:00

  • p53 cannot be induced by hypoxia alone but responds to the hypoxic microenvironment.

    abstract::Solid tumors frequently contain hypoxic subregions due to insufficient blood supply. In these domains, cells can undergo p53-dependent apoptosis. Therefore, hypoxia has been implicated as a physiological stimulus for p53 accumulation and activation. In such an environment, p53 mutant cells exhibit a selective growth a...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1207657

    authors: Pan Y,Oprysko PR,Asham AM,Koch CJ,Simon MC

    更新日期:2004-06-24 00:00:00

  • T-cell acute lymphoblastic leukemia displays autocrine production of Interleukin-7.

    abstract::T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy characterized by an accumulation of immature T cells. Although patient outcomes have improved, novel targeted therapies are needed to reduce the intensity of chemotherapy and improve the prognosis of high-risk patients. Interleukin-7...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/s41388-019-0921-4

    authors: Buffière A,Uzan B,Aucagne R,Hermetet F,Mas M,Nassurdine S,Aznague A,Carmignac V,Tournier B,Bouchot O,Ballerini P,Barata JT,Bastie JN,Delva L,Pflumio F,Quéré R

    更新日期:2019-11-01 00:00:00

  • Fstl1/DIP2A/MGMT signaling pathway plays important roles in temozolomide resistance in glioblastoma.

    abstract::Temozolomide was recognized as the first-line therapy for glioblastoma to prolong the survival of patients noticeably, while recent clinical studies found that some patients were not sensitive to temozolomide treatment. The possible mechanisms seemed to be methylguanine-DNA-methyltransferase (MGMT), mismatch repair, P...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/s41388-018-0596-2

    authors: Nie E,Miao F,Jin X,Wu W,Zhou X,Zeng A,Yu T,Zhi T,Shi Z,Wang Y,Zhang J,Liu N,You Y

    更新日期:2019-04-01 00:00:00

  • A role for Ubc9 in tumorigenesis.

    abstract::The post-translational modifications ubiquitination and sumoylation have been implicated in regulating many critical cellular pathways. Like ubiquitination, sumoylation is a multistep process involving maturation, activation, conjugation and deconjugation. Ubc9 is a sole E2-conjugating enzyme essential for sumoylation...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1208210

    authors: Mo YY,Yu Y,Theodosiou E,Ee PL,Beck WT

    更新日期:2005-04-14 00:00:00

  • EGFR mutants found in non-small cell lung cancer show different levels of sensitivity to suppression of Src: implications in targeting therapy.

    abstract::Mutations in epidermal growth factor receptor (EGFR) kinase domain associate with clinical responses to EGFR inhibitors and are frequently observed in non-small cell lung cancer (NSCLC) patients in East Asian populations. Clinically identified EGFR mutations cause constitutive receptor activation. The activating mecha...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1210684

    authors: Fu YN,Yeh CL,Cheng HH,Yang CH,Tsai SF,Huang SF,Chen YR

    更新日期:2008-02-07 00:00:00

  • RelB inhibits cell proliferation and tumor growth through p53 transcriptional activation.

    abstract::The alternative nuclear factor-kappaB (NF-κB) -activation pathway proceeds via inducible p100 processing, leading to the activation of RelB-containing dimers. This pathway is aberrantly activated in several types of tumors; however, a direct role for RelB in the control of cell proliferation is still largely unexplore...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2012.282

    authors: Jacque E,Billot K,Authier H,Bordereaux D,Baud V

    更新日期:2013-05-23 00:00:00

  • High-affinity binding and activation of a truncated FGF receptor by both aFGF and bFGF.

    abstract::We recently reported the cloning and overexpression of full-length forms of human fibroblast growth factor (FGF) receptors, bek and flg. These receptors contain three immunoglobulin (Ig)-like domains and an unusual acidic motif in the extracellular region, a single transmembrane segment and a protein tyrosine kinase c...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Crumley G,Bellot F,Kaplow JM,Schlessinger J,Jaye M,Dionne CA

    更新日期:1991-12-01 00:00:00

  • Decreased intranuclear mobility of acute myeloid leukemia 1-containing fusion proteins is accompanied by reduced mobility and compartmentalization of core binding factor beta.

    abstract::Acute myeloid leukemia 1 (AML1) gene on chromosome 21 is involved in several chromosomal translocations, including t(8;21) and t(16;21), that produce chimeric fusion proteins AML1-eight twenty-one (ETO) and AML-myeloid transforming gene chromosome 16 (MTG16), which contribute to leukemogenesis. The molecular basis for...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1209431

    authors: Qiu J,Wong J,Tweardy DJ,Dong S

    更新日期:2006-06-29 00:00:00

  • Formation of PML/RAR alpha high molecular weight nuclear complexes through the PML coiled-coil region is essential for the PML/RAR alpha-mediated retinoic acid response.

    abstract::Retinoic Acid (RA) treatment induces disease remission of Acute Promyelocytic Leukaemia (APL) patients by triggering terminal differentiation of neoplastic cells. RA-sensitivity in APL is mediated by its oncogenic protein, which results from the recombination of the PML and the RA receptor alpha (RAR alpha) genes (PML...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1203029

    authors: Grignani F,Gelmetti V,Fanelli M,Rogaia D,De Matteis S,Ferrara FF,Bonci D,Grignani F,Nervi C,Pelicci PG

    更新日期:1999-11-04 00:00:00

  • Interactions of the DNA mismatch repair proteins MLH1 and MSH2 with c-MYC and MAX.

    abstract::MSH2 and MLH1 have a central role in correcting mismatches in DNA occurring during DNA replication and have been implicated in the engagement of apoptosis induced by a number of cytotoxic anticancer agents. The function of MLH1 is not clearly defined, although it is required for mismatch repair (MMR) and engagement of...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1206252

    authors: Mac Partlin M,Homer E,Robinson H,McCormick CJ,Crouch DH,Durant ST,Matheson EC,Hall AG,Gillespie DA,Brown R

    更新日期:2003-02-13 00:00:00

  • A SOCS-1 peptide mimetic inhibits both constitutive and IL-6 induced activation of STAT3 in prostate cancer cells.

    abstract::Prostate cancer is the second highest cause of cancer-related deaths of men in the US. Signal transducers and activators of transcription (STATs) proteins are a small family of latent cytoplasmic transcription factors that act downstream of Janus kinase (JAK) activation and mediate intracellular signaling from a wide ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1208437

    authors: Flowers LO,Subramaniam PS,Johnson HM

    更新日期:2005-03-17 00:00:00

  • MAGI-3 is involved in the regulation of the JNK signaling pathway as a scaffold protein for frizzled and Ltap.

    abstract::A seven-transmembrane protein, frizzled, has been implicated in a planar cell polarity (PCP) pathway as well as the canonical Wnt signaling pathway. Although both pathways require a cytoplasmic protein, dishevelled, the molecular mechanism by which frizzled regulates intracellular signaling remains to be elucidated. I...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1207817

    authors: Yao R,Natsume Y,Noda T

    更新日期:2004-08-12 00:00:00

  • Amifostine (WR2721) restores transcriptional activity of specific p53 mutant proteins in a yeast functional assay.

    abstract::Many p53 mutants found in human cancer have an altered ability to bind DNA and transactivate gene expression. Re-expression of functional p53 in cells in which the endogenous TP53 gene is inactivated has been demonstrated to restore a non-tumorigenic phenotype. Pharmacological modulation of p53 mutant conformation may...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1204428

    authors: Maurici D,Monti P,Campomenosi P,North S,Frebourg T,Fronza G,Hainaut P

    更新日期:2001-06-14 00:00:00

  • AP-1 complexes containing cJun and JunB cause cellular transformation of Rat1a fibroblasts and share transcriptional targets.

    abstract::To investigate the role of individual Jun proteins in cell growth and transformation, we have used a doxycycline-inducible retroviral vector to regulate their expression in rat fibroblasts. AP-1 complexes enriched with cJun and JunB result in morphological alterations and anchorage-independent cell growth consistent w...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1206644

    authors: Leaner VD,Kinoshita I,Birrer MJ

    更新日期:2003-08-28 00:00:00

  • The PI3K inhibitor GDC-0941 combines with existing clinical regimens for superior activity in multiple myeloma.

    abstract::The phosphatidylinositol 3'-kinase (PI3K) pathway is dysregulated in multiple myeloma (MM); we therefore tested a highly selective class I PI3K inhibitor, GDC-0941, for anti-myeloma activity. Functional and mechanistic studies were first performed in MM cell lines, then extended to primary MM patient samples cultured ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2012.594

    authors: Munugalavadla V,Mariathasan S,Slaga D,Du C,Berry L,Del Rosario G,Yan Y,Boe M,Sun L,Friedman LS,Chesi M,Leif Bergsagel P,Ebens A

    更新日期:2014-01-16 00:00:00

  • Microsatellite instability in prostate cancer.

    abstract::Assessment of the genetic instability of a microsatellite has indicated a new mechanism in human carcinogenesis. Examination was made to determine whether microsatellite instability is associated with the onset of prostate cancer. Twenty-nine DNA samples from 24 primary prostate cancer, two metastatic lymph-node and t...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Uchida T,Wada C,Wang C,Ishida H,Egawa S,Yokoyama E,Ohtani H,Koshiba K

    更新日期:1995-03-02 00:00:00

  • SYK interaction with ITGβ4 suppressed by Epstein-Barr virus LMP2A modulates migration and invasion of nasopharyngeal carcinoma cells.

    abstract::Epstein-Barr virus (EBV)-encoded Latent Membrane Protein 2A (LMP2A) is an EBV latency-associated protein regularly expressed in nasopharyngeal carcinoma (NPC). In B cells, LMP2A activity resembles that of a constitutively activated antigen receptor, which recruits the Syk tyrosine kinase to activate a set of downstrea...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2014.380

    authors: Zhou X,Matskova L,Rathje LS,Xiao X,Gish G,Werner M,Ignatyev I,Yu N,Zhao W,Tian F,Hou B,Zhang Z,Pawson T,Chen F,Ernberg I

    更新日期:2015-08-20 00:00:00

  • Roles of heat shock factor 1 and 2 in response to proteasome inhibition: consequence on p53 stability.

    abstract::A single heat shock factor (HSF), mediating the heat shock response, exists from yeast to Drosophila, whereas several related HSFs have been found in mammals. This raises the question of the specific or redundant functions of the different members of the HSF family and in particular of HSF1 and HSF2, which are both ub...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2010.171

    authors: Lecomte S,Desmots F,Le Masson F,Le Goff P,Michel D,Christians ES,Le Dréan Y

    更新日期:2010-07-22 00:00:00

  • hRAD17, a structural homolog of the Schizosaccharomyces pombe RAD17 cell cycle checkpoint gene, stimulates p53 accumulation.

    abstract::The RAD17 gene product of S. Pombe is an essential component of the checkpoint control pathway which responds to both DNA damage and disruption of replication. We have identified a human cDNA that encodes a polypeptide which is structurally conserved with the S. Pombe Rad17 protein. The human gene, designated hRAD17, ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1202469

    authors: Li L,Peterson CA,Kanter-Smoler G,Wei YF,Ramagli LS,Sunnerhagen P,Siciliano MJ,Legerski RJ

    更新日期:1999-03-04 00:00:00

  • Stem cell programs are retained in human leukemic lymphoblasts.

    abstract::Leukemic lymphoblasts within different immunophenotypic populations possess stem cell properties. However, whether or not the self-renewal program is retained from stem cells or conferred on progenitors by leukemogenic molecules remains unknown. We have addressed the issue in the context of TEL-AML1-associated acute l...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2014.148

    authors: Fan D,Zhou X,Li Z,Li ZQ,Duan C,Liu T,Zhang F,Huang Y,Zhang Y,Gao F,Guo Y,Gupta R,Chen G,Enver T,Tang J,Hong D

    更新日期:2015-04-16 00:00:00

  • Activation and repression of p21(WAF1/CIP1) transcription by RB binding proteins.

    abstract::The Cdk inhibitor p21(WAF1/CIP1) is a negative regulator of the cell cycle, although its expression is induced by a number of mitogens that promote cell proliferation. We have found that E2F1 and E2F3, transcription factors that activate genes required for cell cycle progression, are strong activators of the p21 promo...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1202240

    authors: Gartel AL,Goufman E,Tevosian SG,Shih H,Yee AS,Tyner AL

    更新日期:1998-12-31 00:00:00

  • Human T-cell leukemia virus type 1 Tax protein induces the expression of STAT1 and STAT5 genes in T-cells.

    abstract::Human T-cell leukemia virus type 1 (HTLV-1) Tax transforms normal T-cells in the presence of interleukin (IL)-2 in vitro. STAT is a family of transcription factors that play a pivotal role in cytokine-induced functions of a various type of cells. We investigated the involvement of STATs in the transformation of T-cell...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1202608

    authors: Nakamura N,Fujii M,Tsukahara T,Arai M,Ohashi T,Wakao H,Kannagi M,Yamamoto N

    更新日期:1999-04-29 00:00:00

  • Increase in specific DNA binding by carboxyl truncation suggests a mechanism for activation of Myb.

    abstract::Oncogenic forms of the c-myb protein (Myb) often exhibit amino-terminal and/or carboxyl-terminal truncations. When the transcriptional activity of these proteins was examined it was found that carboxyl-truncated Myb is more effective as a transcriptional activator than full-length or amino-truncated Myb. In order to d...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Ramsay RG,Ishii S,Gonda TJ

    更新日期:1991-10-01 00:00:00

  • A proprotein convertase/MMP-14 proteolytic cascade releases a novel 40 kDa vasculostatin from tumor suppressor BAI1.

    abstract::Brain-specific angiogenesis inhibitor 1 (BAI1), an orphan G protein-coupled receptor-type seven transmembrane protein, was recently found mutated or silenced in multiple human cancers and can interfere with tumor growth when overexpressed. Yet, little is known about its regulation and the molecular mechanisms through ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2012.1

    authors: Cork SM,Kaur B,Devi NS,Cooper L,Saltz JH,Sandberg EM,Kaluz S,Van Meir EG

    更新日期:2012-12-13 00:00:00

  • Antibody targeting of anaplastic lymphoma kinase induces cytotoxicity of human neuroblastoma.

    abstract::Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase aberrantly expressed in neuroblastoma, a devastating pediatric cancer of the sympathetic nervous system. Germline and somatically acquired ALK aberrations induce increased autophosphorylation, constitutive ALK activation and increased downstream signaling....

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2011.647

    authors: Carpenter EL,Haglund EA,Mace EM,Deng D,Martinez D,Wood AC,Chow AK,Weiser DA,Belcastro LT,Winter C,Bresler SC,Vigny M,Mazot P,Asgharzadeh S,Seeger RC,Zhao H,Guo R,Christensen JG,Orange JS,Pawel BR,Lemmon MA,Mossé

    更新日期:2012-11-15 00:00:00

  • The amino-terminal half of pp59c-fyn contains sequences necessary for formation of a 75 kDa form and also repressive elements absent in pp60c-src.

    abstract::Members of the src family of tyrosine kinases are composed of amino acid sequences which can be divided into three regions: the unique amino-terminal 80 residues; the next 180 residues of conserved but non-catalytic sequence; and the catalytic carboxy-terminal half of the molecule. To characterize the elements that re...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Espino PC,Chou WY,Smith AE,Cheng SH

    更新日期:1992-02-01 00:00:00