Gene amplification-associated overexpression of the RNA editing enzyme ADAR1 enhances human lung tumorigenesis.

Abstract:

:The introduction of new therapies against particular genetic mutations in non-small-cell lung cancer is a promising avenue for improving patient survival, but the target population is small. There is a need to discover new potential actionable genetic lesions, to which end, non-conventional cancer pathways, such as RNA editing, are worth exploring. Herein we show that the adenosine-to-inosine editing enzyme ADAR1 undergoes gene amplification in non-small cancer cell lines and primary tumors in association with higher levels of the corresponding mRNA and protein. From a growth and invasion standpoint, the depletion of ADAR1 expression in amplified cells reduces their tumorigenic potential in cell culture and mouse models, whereas its overexpression has the opposite effects. From a functional perspective, ADAR1 overexpression enhances the editing frequencies of target transcripts such as NEIL1 and miR-381. In the clinical setting, patients with early-stage lung cancer, but harboring ADAR1 gene amplification, have poor outcomes. Overall, our results indicate a role for ADAR1 as a lung cancer oncogene undergoing gene amplification-associated activation that affects downstream RNA editing patterns and patient prognosis.

journal_name

Oncogene

journal_title

Oncogene

authors

Anadón C,Guil S,Simó-Riudalbas L,Moutinho C,Setien F,Martínez-Cardús A,Moran S,Villanueva A,Calaf M,Vidal A,Lazo PA,Zondervan I,Savola S,Kohno T,Yokota J,Ribas de Pouplana L,Esteller M

doi

10.1038/onc.2015.469

subject

Has Abstract

pub_date

2016-08-18 00:00:00

pages

4407-13

issue

33

eissn

0950-9232

issn

1476-5594

pii

onc2015469

journal_volume

35

pub_type

杂志文章

相关文献

ONCOGENE文献大全
  • MutT Homolog 1 (MTH1) maintains multiple KRAS-driven pro-malignant pathways.

    abstract::Oncogenic RAS promotes production of reactive oxygen species (ROS), which mediate pro-malignant signaling but can also trigger DNA damage-induced tumor suppression. Thus RAS-driven tumor cells require redox-protective mechanisms to mitigate the damaging aspects of ROS. Here, we show that MutT Homolog 1 (MTH1), the mam...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2014.195

    authors: Patel A,Burton DG,Halvorsen K,Balkan W,Reiner T,Perez-Stable C,Cohen A,Munoz A,Giribaldi MG,Singh S,Robbins DJ,Nguyen DM,Rai P

    更新日期:2015-05-14 00:00:00

  • Studying the pathogenesis of BCR-ABL+ leukemia in mice.

    abstract::Animal models of BCR-ABL+ leukemias have provided important new knowledge about the molecular pathophysiology of these diseases, and answered questions that are difficult or impossible to address using BCR-ABL-expressing cell lines or primary Ph+ leukemia samples from patients. The power of mouse models lies in their ...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:10.1038/sj.onc.1206091

    authors: Van Etten RA

    更新日期:2002-12-09 00:00:00

  • Two wnt genes in Caenorhabditis elegans.

    abstract::wnt genes encode secretory glycoproteins that have been implicated in growth control and development in mice, frogs and insects. In this report we examine properties of two wnt genes recently identified in the nematode Caenorhabditis elegans. The first gene, Ce-wnt-1, was previously identified by a polymerase chain re...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Shackleford GM,Shivakumar S,Shiue L,Mason J,Kenyon C,Varmus HE

    更新日期:1993-07-01 00:00:00

  • Distinct changes in gene expression induced by A-Myb, B-Myb and c-Myb proteins.

    abstract::The c-Myb, A-Myb and B-Myb transcription factors have nearly identical DNA-binding domains, activate the same reporter gene constructs in animal cells, but have different biological roles. The Myb proteins are often coexpressed in the same cells, raising questions about whether they activate similar or distinct gene e...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1206131

    authors: Rushton JJ,Davis LM,Lei W,Mo X,Leutz A,Ness SA

    更新日期:2003-01-16 00:00:00

  • The NF-κB subunit c-Rel regulates Bach2 tumour suppressor expression in B-cell lymphoma.

    abstract::The REL gene, encoding the NF-κB subunit c-Rel, is frequently amplified in B-cell lymphoma and functions as a tumour-promoting transcription factor. Here we report the surprising result that c-rel-/- mice display significantly earlier lymphomagenesis in the c-Myc driven, Eμ-Myc model of B-cell lymphoma. c-Rel loss als...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2015.399

    authors: Hunter JE,Butterworth JA,Zhao B,Sellier H,Campbell KJ,Thomas HD,Bacon CM,Cockell SJ,Gewurz BE,Perkins ND

    更新日期:2016-06-30 00:00:00

  • Differential contributions of ERK and PI3-kinase to the regulation of cyclin D1 expression and to the control of the G1/S transition in mouse embryonic stem cells.

    abstract::Mouse embryonic stem (ES) cells are known to express D-type cyclins at very low levels and these levels increase dramatically during in vitro and in vivo differentiation. Here, we investigate some of the signalling pathways regulating expression of cyclin D1 and progression to S phase, the Ras/Extracellular signal-reg...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1205728

    authors: Jirmanova L,Afanassieff M,Gobert-Gosse S,Markossian S,Savatier P

    更新日期:2002-08-15 00:00:00

  • Mitochondrial DNA mutations in human cancer.

    abstract::Somatic mitochondrial DNA (mtDNA) mutations have been increasingly observed in primary human cancers. As each cell contains many mitochondria with multiple copies of mtDNA, it is possible that wild-type and mutant mtDNA can co-exist in a state called heteroplasmy. During cell division, mitochondria are randomly distri...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:10.1038/sj.onc.1209604

    authors: Chatterjee A,Mambo E,Sidransky D

    更新日期:2006-08-07 00:00:00

  • Snail silencing effectively suppresses tumour growth and invasiveness.

    abstract::The transcription factor Snail has been recently proposed as an important mediator of tumour invasion because of its role in downregulation of E-cadherin and induction of epithelial-mesenchymal transitions (EMT). This behaviour has led to the consideration of Snail as a potential therapeutic target to block tumour pro...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1209997

    authors: Olmeda D,Jordá M,Peinado H,Fabra A,Cano A

    更新日期:2007-03-22 00:00:00

  • C-Jun N-terminal kinases are required for oncolytic adenovirus-mediated autophagy.

    abstract::Oncolytic adenoviruses, such as Delta-24-RGD (Δ24RGD), are replication-competent viruses that are genetically engineered to induce selective cancer cell lysis. In cancer cells, Δ24RGD induces massive autophagy, which is required for efficient cell lysis and adenoviral spread. Understanding the cellular mechanisms unde...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2014.452

    authors: Klein SR,Piya S,Lu Z,Xia Y,Alonso MM,White EJ,Wei J,Gomez-Manzano C,Jiang H,Fueyo J

    更新日期:2015-10-08 00:00:00

  • Endoreplication in megakaryoblastic cell lines is accompanied by sustained expression of G1/S cyclins and downregulation of cdc25C.

    abstract::In most eukaryotic cells, a link between S and M phases of the cell cycle must be assured in order to maintain the ploidy of newly divided cells. However, in some cell l/pes, e.g. the precursors of platelets megakaryocytes, extra S-phases can occur in the absence of concomitant mitoses, resulting in polyploidy. We hav...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: García P,Calés C

    更新日期:1996-08-15 00:00:00

  • Different interactions of Grb2/Ash molecule with the NGF and EGF receptors in rat pheochromocytoma PC12 cells.

    abstract::We have previously shown that nerve growth factor (NGF) induces a rapid and relatively continuous activation of Ras in rat pheochromocytoma PC12 cells while epidermal growth factor (EGF) activates Ras transiently, and that tyrosine kinase activity of the NGF receptor is essential for the activation of Ras (Muroya et a...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Hashimoto Y,Matuoka K,Takenawa T,Muroya K,Hattori S,Nakamura S

    更新日期:1994-03-01 00:00:00

  • The N-terminal common domain of simian virus 40 large T and small t antigens acts as a transformation suppressor of the HER-2/neu oncogene.

    abstract::Overexpression of HER-2/neu (also known as c-erbB-2) proto-oncogene frequently occurs in many different types of human cancers, including ovarian carcinoma, and is known to enhance tumor metastasis and chemoresistance. Previous studies showed that inhibition of HER-2/neu expression by various agents, such as adenoviru...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1203582

    authors: Lin YC,Peng JM,Wang WB

    更新日期:2000-05-18 00:00:00

  • Autocrine HGF/c-Met signaling pathway confers aggressiveness in lymph node adult T-cell leukemia/lymphoma.

    abstract::Adult T-cell leukemia/lymphoma (ATL) is an aggressive T-cell neoplasm. While ATL cells in peripheral blood (PB-ATL) are sensitive to anti-CC chemokine receptor 4 treatment, non-PB-ATLs, including lymph node ATLs (LN-ATLs), are more aggressive and resistant. We examined characteristic cytokines and growth factors that ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/s41388-020-01393-x

    authors: Totani H,Shinjo K,Suzuki M,Katsushima K,Mase S,Masaki A,Ito A,Ri M,Kusumoto S,Komatsu H,Ishida T,Inagaki H,Iida S,Kondo Y

    更新日期:2020-08-01 00:00:00

  • Hsp90-inhibitor geldanamycin abrogates G2 arrest in p53-negative leukemia cell lines through the depletion of Chk1.

    abstract::Checkpoint protein Chk1 has been identified as an Hsp90 client. Treatment with 100 nM geldanamycin (GM) for 24 h markedly reduced the Chk1 amount in Jurkat and ML-1 leukemia cell lines. Because Chk1 plays a central role in G2 checkpoint, we added GM to G2-arrested Jurkat and HL-60 cells pretreated with 50 nM doxorubic...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1210978

    authors: Sugimoto K,Sasaki M,Isobe Y,Tsutsui M,Suto H,Ando J,Tamayose K,Ando M,Oshimi K

    更新日期:2008-05-15 00:00:00

  • A RasGAP-derived cell permeable peptide potently enhances genotoxin-induced cytotoxicity in tumor cells.

    abstract::Treatment of many cancers relies on the combined action of several genotoxins, but the detrimental effect of these drugs on normal cells can cause severe side effects. One major challenge in anticancer therapy is therefore to increase the selectivity of current treatments toward cancer cells in order to spare normal c...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1207999

    authors: Michod D,Yang JY,Chen J,Bonny C,Widmann C

    更新日期:2004-11-25 00:00:00

  • Ras adenoviruses modulate cyclin E protein expression and DNA synthesis after partial hepatectomy.

    abstract::Ras-genes encode for proteins important for transmitting extracellular signals from the cytoplasm to the nucleus. In this study we investigated the impact of Ras on cell cycle progression after hepatectomy by using adenoviral vectors (adv) expressing beta-galactosidase (beta-gal), a dominant-negative (Ras N17) or a do...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1204690

    authors: Lüdde T,Kubicka S,Plümpe J,Liedtke C,Manns MP,Trautwein C

    更新日期:2001-08-30 00:00:00

  • COL11A1 promotes tumor progression and predicts poor clinical outcome in ovarian cancer.

    abstract::Biomarkers that predict disease progression might assist the development of better therapeutic strategies for aggressive cancers, such as ovarian cancer. Here, we investigated the role of collagen type XI alpha 1 (COL11A1) in cell invasiveness and tumor formation and the prognostic impact of COL11A1 expression in ovar...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2013.307

    authors: Wu YH,Chang TH,Huang YF,Huang HD,Chou CY

    更新日期:2014-06-26 00:00:00

  • EGFR-dependent pancreatic carcinoma cell metastasis through Rap1 activation.

    abstract::Tyrosine kinase receptors have an essential role in various aspects of tumor progression. In particular, epidermal growth factor receptor (EGFR) and its ligands have been implicated in the growth and dissemination of a wide array of human carcinomas. Here, we describe an EGFR-mediated signaling pathway that regulates ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2011.450

    authors: Huang M,Anand S,Murphy EA,Desgrosellier JS,Stupack DG,Shattil SJ,Schlaepfer DD,Cheresh DA

    更新日期:2012-05-31 00:00:00

  • Matrilysin (MMP-7) induces homotypic adhesion of human colon cancer cells and enhances their metastatic potential in nude mouse model.

    abstract::Matrilysin (MMP-7) is thought to contribute to invasive growth and metastasis of colon carcinoma and many other human cancers. The present study demonstrates that treatment of human colon carcinoma cells with active matrilysin induces cell aggregation in vitro and promotes liver metastasis in nude mice. When two kinds...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1207181

    authors: Kioi M,Yamamoto K,Higashi S,Koshikawa N,Fujita K,Miyazaki K

    更新日期:2003-11-27 00:00:00

  • RNH1 regulation of reactive oxygen species contributes to histone deacetylase inhibitor resistance in gastric cancer cells.

    abstract::Histone deacetylase inhibitors (HDACis) are a promising class of anticancer epigenetic drugs, however, molecular factors influencing the responses of individual tumors to HDACi therapies remain obscure. Here, we sought to identify genes associated with HDACi resistance in gastric cancer. Treating a panel of 17 gastric...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2013.104

    authors: Zhu Y,Das K,Wu J,Lee MH,Tan P

    更新日期:2014-03-20 00:00:00

  • Use of the two hybrid system to detect the association of the protein-tyrosine-phosphatase, SHPTP2, with another SH2-containing protein, Grb7.

    abstract::SHPTP2 is a ubiquitously-expressed SH2-containing tyrosine phosphatase that is tyrosine phosphorylated in response to activation of various receptor and nonreceptor tyrosine kinases. SHPTP2 associates with the platelet-derived growth factor (PDGF) receptor after ligand stimulation, and binding of SHPTP2 to this recept...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Keegan K,Cooper JA

    更新日期:1996-04-04 00:00:00

  • Estrogen receptor positivity in mammary tumors of Wnt-1 transgenic mice is influenced by collaborating oncogenic mutations.

    abstract::The majority (75%) of human breast cancers express estrogen receptor (ER). Although ER-positive tumors usually respond to antiestrogen therapies, 30% of them do not. It is not known what controls the ER status of breast cancers or their responsiveness to antihormone interventions. In this report, we document that tran...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1208597

    authors: Zhang X,Podsypanina K,Huang S,Mohsin SK,Chamness GC,Hatsell S,Cowin P,Schiff R,Li Y

    更新日期:2005-06-16 00:00:00

  • Overexpression confers an oncogenic potential upon the eph gene.

    abstract::The eph gene encodes a putative receptor tyrosine kinase for an as yet unknown ligand. Some human cancer cells have been found to overexpress eph mRNAs without gene amplification. We show here that NIH3T3 cells acquire tumorigenic ability in nude mice and make colonies in soft agar with a viral LTR (Long Terminal Repe...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Maru Y,Hirai H,Takaku F

    更新日期:1990-03-01 00:00:00

  • Ubiquilin1 represses migration and epithelial-to-mesenchymal transition of human non-small cell lung cancer cells.

    abstract::Ubiquilin1 (UBQLN1) is a ubiquitin-like domain and a ubiquitin-associated domain containing protein that has been reported to be involved in shuttling proteins to the proteasome, especially during endoplasmic reticulum-associated protein degradation. Thus, UBQLN1 function has been shown to be critical for combating a ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2014.97

    authors: Shah PP,Lockwood WW,Saurabh K,Kurlawala Z,Shannon SP,Waigel S,Zacharias W,Beverly LJ

    更新日期:2015-03-26 00:00:00

  • HPV E2, E4, E5 drive alternative carcinogenic pathways in HPV positive cancers.

    abstract::The dominant paradigm for HPV carcinogenesis includes integration into the host genome followed by expression of E6 and E7 (E6/E7). We explored an alternative carcinogenic pathway characterized by episomal E2, E4, and E5 (E2/E4/E5) expression. Half of HPV positive cervical and pharyngeal cancers comprised a subtype wi...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/s41388-020-01431-8

    authors: Ren S,Gaykalova DA,Guo T,Favorov AV,Fertig EJ,Tamayo P,Callejas-Valera JL,Allevato M,Gilardi M,Santos J,Fukusumi T,Sakai A,Ando M,Sadat S,Liu C,Xu G,Fisch KM,Wang Z,Molinolo AA,Gutkind JS,Ideker T,Koch WM,Cali

    更新日期:2020-10-01 00:00:00

  • RFP represses transcriptional activation by bHLH transcription factors.

    abstract::Basic helix-loop-helix (bHLH) transcription factors play a pivotal role in the regulation of tumorigenesis, and also in a wide range of other developmental processes in diverse species from yeast to humans. Here we demonstrate for the first time that Ret finger protein (RFP), a member of the TRIM family of proteins in...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1208828

    authors: Bloor AJ,Kotsopoulou E,Hayward P,Champion BR,Green AR

    更新日期:2005-10-13 00:00:00

  • Mechanisms of transcriptional transactivation and restriction of human immunodeficiency virus type I replication in an astrocytic glial cell.

    abstract::Unique transcriptional transactivation by the human immunodeficiency virus type 1 (HIV-1) Tat protein of long terminal repeat (LTR)-driven RNA expression, in the absence of the transactivator responsive element (TAR), was previously demonstrated in central nervous system (CNS)-derived astrocytic cell-lines, including ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Niikura M,Dornadula G,Zhang H,Mukhtar M,Lingxun D,Khalili K,Bagasra O,Pomerantz RJ

    更新日期:1996-07-18 00:00:00

  • TAT-apoptin is efficiently delivered and induces apoptosis in cancer cells.

    abstract::Apoptin has been described to induce apoptosis in various human cancer cell lines, but not in normal cells, thus making it an interesting candidate for the development of novel therapeutic strategies. Apoptin was generated and cloned into several mammalian expression vectors. Transfection or microinjection of apoptin ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1207224

    authors: Guelen L,Paterson H,Gäken J,Meyers M,Farzaneh F,Tavassoli M

    更新日期:2004-02-05 00:00:00

  • In vitro genetic screen identifies a cooperative role for LPA signaling and c-Myc in cell transformation.

    abstract::c-Myc drives uncontrolled cell proliferation in various human cancers. However, in mouse embryo fibroblasts (MEFs), c-Myc also induces apoptosis by activating the p19Arf tumor suppressor pathway. Tbx2, a transcriptional repressor of p19Arf, can collaborate with c-Myc by suppressing apoptosis. MEFs overexpressing c-Myc...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2008.294

    authors: Taghavi P,Verhoeven E,Jacobs JJ,Lambooij JP,Stortelers C,Tanger E,Moolenaar WH,van Lohuizen M

    更新日期:2008-11-20 00:00:00

  • Alpha-fetoprotein producing gastric cancer lacks transcription factor ATBF1.

    abstract::Alpha-fetoprotein (AFP) producing gastric cancer (AFP-GC) is very malignant and highly metastatic compared with common gastric cancer. However, the causal relationship between AFP production and the high malignancy of AFP-GC is unclear. We investigated AFP gene regulation in AFP-GC by an active transcription factor, H...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1204160

    authors: Kataoka H,Miura Y,Joh T,Seno K,Tada T,Tamaoki T,Nakabayashi H,Kawaguchi M,Asai K,Kato T,Itoh M

    更新日期:2001-02-15 00:00:00