Abstract：
:Persistent infection by high-risk human papillomaviruses (HPVs) is associated with the development of cervical cancer and a subset of anogenital and head and neck squamous cell carcinomas. Abnormal expression of cellular microRNAs (miRNAs) plays an important role in the development of cancer, including HPV-related tumors. In this study, we demonstrated that miR-146a-5p was down-regulated by E6 and, less efficiently, by E7 of high-risk HPV16 in keratinocytes and the presence of low levels of this miRNA in cervical carcinoma cell lines and in high-risk HPV-positive cervical specimens. Down-regulation of miR-146a-5p was mediated at least in part by the transcription repressor c-MYC, through binding sites in the miR-146a promoter. Overexpression of miR-146a-5p significantly inhibited proliferation and migration of keratinocytes and cervical cancer cells. The histone demethylase KDM2B was validated as a new direct target of miR-146a-5p and two putative binding sites for miR-146a-5p were identified in its 3'UTR sequence. Western blot analysis and immunohistochemistry showed that KDM2B was overexpressed in HPV16 E6/E7-positive keratinocytes, in cervical cancer cell lines, and in a subset of invasive cervical carcinomas and HPV-positive laryngeal squamous cell carcinomas. In these tumors, KDM2B overexpression was associated with c-MYC copy number gain. In vitro, silencing of KDM2B inhibited proliferation of cervical cancer cells. In conclusion, this study identified a novel player, the hystone demethylase KDM2B, in HPV-mediated tumorigenesis. E6 and, less efficiently, E7 of high-risk HPV16 up-regulated KDM2B expression in human keratinocytes through a pathway involving overexpression of c-MYC, which in turn downregulated miR-146a-5p.
journal_name
Oncogenejournal_title
Oncogeneauthors
Peta E,Sinigaglia A,Masi G,Di Camillo B,Grassi A,Trevisan M,Messa L,Loregian A,Manfrin E,Brunelli M,Martignoni G,Palù G,Barzon Ldoi
10.1038/s41388-017-0083-1subject
Has Abstractpub_date
2018-03-01 00:00:00pages
1654-1668issue
12eissn
0950-9232issn
1476-5594pii
10.1038/s41388-017-0083-1journal_volume
37pub_type
杂志文章相关文献
ONCOGENE文献大全abstract：:We previously described the isolation of non-tumorigenic revertants from mutagenized populations of v-fos-transformed Rat-1 cells (Zarbl et al., 1987). In the present study we examined the possibility that the revertant phenotype resulted from mutations that altered the expression or activities of the c-jun or junB pr...
journal_title：Oncogene
pub_type： 杂志文章
doi：
更新日期：1994-10-01 00:00:00
abstract：:Like other types of pre-malignant lesions and carcinoma, angiogenesis is associated with high-grade cervical dysplasia and with invasive squamous carcinoma of the cervix. Vascular endothelial cell growth factor (VEGF) is known to be one of the most important inducers of angiogenesis and is upregulated in carcinoma of ...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/sj.onc.1203817
更新日期：2000-09-21 00:00:00
abstract：:The hypoxia-inducible factor 1 (HIF-1) plays a critical role for tumour adaptation to microenvironmental hypoxia, and represents an appealing chemotherapeutic target. Silibinin is a nontoxic flavonoid reported to exhibit anticancer properties. However, the mechanisms by which silibinin inhibits tumour growth are not f...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/onc.2008.398
更新日期：2009-01-22 00:00:00
abstract：:Ubiquitin-dependent mechanisms have emerged as essential regulatory elements controlling cellular levels of Smads and TGFβ-dependent biological outputs such as epithelial-mesenchymal transition (EMT). In this study, we identify a HECT E3 ubiquitin ligase known as WWP2 (Full-length WWP2-FL), together with two WWP2 isof...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/onc.2010.617
更新日期：2011-05-26 00:00:00
abstract：:The RBTN1 and RBTN2 genes are activated by distinct translocations involving chromosome 11 in some T cell acute leukaemias. The RBTN proteins belong to the LIM family which comprises proteins with one, two or three cysteine-rich LIM domains, sometimes together with homeodomains or protein kinase domains. The RBTN1 and...
journal_title：Oncogene
pub_type： 杂志文章
doi：
更新日期：1995-04-06 00:00:00
abstract：:Kaposi's sarcoma-associated herpesvirus (KSHV) K13/vFLIP (viral Flice-inhibitory protein) induces transcription of numerous genes through NF-κB activation, including pro-inflammatory cytokines, which contribute to the pathogenesis of Kaposi's sarcoma (KS). In this study, we report that KSHV vFLIP induces the expressio...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/onc.2012.145
更新日期：2013-03-07 00:00:00
abstract：:The DNA-binding, transcriptional activation and transforming activities of the Myc protein require dimerization with Max. Max can form also homodimers which are able to bind the same DNA sequence as Myc/Max heterodimers and suppress Myc-induced transcription and transformation. We have recently identified a naturally ...
journal_title：Oncogene
pub_type： 杂志文章
doi：
更新日期：1995-08-03 00:00:00
abstract：:Numerous reports suggest that use of nonsteroidal anti-inflammatory drugs (NSAIDs) decrease mortality from colorectal cancer. To better understand all of the mechanisms underlying this effect, the global pattern of gene expression in colon carcinoma cells following treatment with NS-398, a selective cyclo-oxygenase-2 ...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/sj.onc.1204588
更新日期：2001-07-27 00:00:00
abstract：:Better understanding of the underlying biology of malignant gliomas is critical for the development of early detection strategies and new therapeutics. This study aimed to define genes associated with survival. We investigated whether genes coupled with a class prediction model could be used to define subgroups of hig...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/sj.onc.1209585
更新日期：2006-09-28 00:00:00
abstract：:FHIT (Fragile Histidine Triad), a putative tumor suppressor gene, was cloned from fetal brain and colon cDNA libraries. Portions of this gene are deleted in esophageal, colon, lung and breast tumors, but this gene has not been found altered in sporadic renal cell carcinomas. We report here an alternatively spliced for...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/sj.onc.1201164
更新日期：1997-07-03 00:00:00
abstract：:Transforming Growth Factor-beta1 (TGF-beta1) inhibits the proliferation of most cells, but stimulates some mesenchymal cell types, including murine NIH3T3 fibroblasts. We show here that TGF-beta1 growth stimulation of NIH3T3 fibroblasts is reversed when these cells are transformed by SV40 or are transfected with a pla...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/sj.onc.1202341
更新日期：1999-01-21 00:00:00
abstract：:Damage induced in the DNA after exposure of cells to ionizing radiation activates checkpoint pathways that inhibit progression of cells through the G1 and G2 phases and induce a transient delay in the progression through S phase. Checkpoints together with repair and apoptosis are integrated in a circuitry that determi...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/sj.onc.1206682
更新日期：2003-09-01 00:00:00
abstract：:A minimal transcription activation domain of the v-Myb oncoprotein was initially mapped to a central cluster of charged residues using GAL4-Myb fusion proteins. This region has been proposed to interact directly with the CBP co-activator in animal cells. Regions flanking this central domain of v-Myb are required for t...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/sj.onc.1205236
更新日期：2002-02-28 00:00:00
abstract：:The c-Myc transcription factor activates a cascade of downstream targets to form a complex transcriptional program that ultimately leads to cellular transformation. Although a large number of protein-encoding genes as well as non-coding RNAs were identified as Myc targets, only a few have been validated to be function...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/onc.2010.602
更新日期：2011-05-12 00:00:00
abstract：:Breast cancer cells that overexpress HER-2/neu are more resistant to chemotherapeutic agents such as paclitaxel (Taxol) and docetaxel (Taxotere) than those that do not overexpress HER-2/neu. In previous work, we showed that the adenovirus type 5 E1A can repress HER-2/neu expression at the transcriptional level. Here w...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/sj.onc.1201250
更新日期：1997-08-18 00:00:00
abstract：:Histone acetylation has a central role in establishing an active chromatin environment. The functional contribution of histone acetylation to chromatin transcription is accomplished by a dominant action of histone acetyltransferases over repressive histone-modifying activities at gene promoters; misregulation of these...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/onc.2012.273
更新日期：2013-05-16 00:00:00
abstract：:The p53 tumour suppressor induces cell cycle arrest and apoptosis in response to cellular stresses. p53 is inactivated by various cellular and viral factors. We set out to generate regulatable p53 derivatives that are highly inducible by synthetic ligands, escape inactivation and efficiently induce apoptosis. We have ...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/sj.onc.1203256
更新日期：2000-01-20 00:00:00
abstract：:The short isoform of single-minded 2 (SIM2s), a basic helix-loop-helix/PAS (bHLH/PAS) transcription factor, is upregulated in pancreatic and prostate tumours; however, a mechanistic role for SIM2s in these cancers is unknown. Microarray studies in prostate DU145 cells identified the pro-cell death gene, BNIP3 (Bcl-2/a...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/onc.2009.228
更新日期：2009-10-15 00:00:00
abstract：:As part of a cloning strategy to identify genes involved in early mouse liver development we have isolated Praja1, a gene with similar sequences to the Drosophila melanogaster gene goliath (gl) which is involved in the fate of mesodermal cells ultimately forming gut musculatures, fat body, and the heart. Praja1 is a 2...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/sj.onc.1201405
更新日期：1997-11-06 00:00:00
abstract：:We have examined the mitogenic potential of platelet-derived growth factor (PDGF) on AIDS (acquired immune deficiency syndrome)-related and sporadic Kaposi's sarcoma cells in comparison to fibroblasts at physiological and subphysiological calcium concentrations of the culture medium. At low calcium concentrations in t...
journal_title：Oncogene
pub_type： 杂志文章
doi：
更新日期：1989-04-01 00:00:00
abstract：:Hedgehog (Hh) is an oncogenic signaling pathway that regulates the activity of Gli transcription factors. Canonical Hh is a Smoothened- (Smo-) driven process that alters the post-translational processing of Gli2/Gli3 proteins. Though evidence supports a role for Gli action in prostate cancer (PCa) cell growth and prog...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/s41388-017-0098-7
更新日期：2018-04-01 00:00:00
abstract：:Triple-negative breast cancers (TNBCs) are characterized by a poor prognosis and lack of targeted treatments, and thus, new therapeutic strategies are urgently needed. Inhibitors against programmed death-1 (PD-1)/PD-1 ligand (PD-L1) have shown significant efficacy in various solid cancers, but their activity against T...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/s41388-019-0700-2
更新日期：2019-05-01 00:00:00
abstract：:BCR-ABL1 is a fusion tyrosine kinase, which causes multiple types of leukemia. We used an integrated proteomic approach that includes label-free quantitative protein complex and phosphorylation profiling by mass spectrometry to systematically characterize the proximal signaling network of this oncogenic kinase. The pr...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/onc.2010.331
更新日期：2010-11-04 00:00:00
abstract：:Chronic infection by hepatitis C virus (HCV) is a major risk factor for the onset and development of hepatocellular carcinoma (HCC), although the underlying mechanisms are unclear. The c-Myc oncogene contributes to the genesis of many types of cancers, including HCC, partly via the induction of genetic damage and the ...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/onc.2012.484
更新日期：2013-09-26 00:00:00
abstract：:Transgenic mice expressing the c-Myc oncogene driven by woodchuck hepatitis virus (WHV) regulatory sequences develop hepatocellular carcinoma with a high frequency. To investigate genetic lesions that cooperate with Myc in liver carcinogenesis, we conducted a genome-wide scan for loss of heterozygosity (LOH) and mutat...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/sj.onc.1205208
更新日期：2002-02-28 00:00:00
abstract：:Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer among men in the developed world. There is a need, for both clinical and scientific reasons, to find markers to identify patients with aggressive disease as early as possible, and to understand the events leading to malignant transformation ...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/sj.onc.1207345
更新日期：2004-04-01 00:00:00
abstract：:The recent identification of the mouse White spotting and Steel loci as genes encoding the c-kit receptor and its ligand, respectively, has shed light on the importance of this ligand and receptor in embryogenesis, melanogenesis and hematopoiesis. In order to determine if the c-kit proto-oncogene is involved in human ...
journal_title：Oncogene
pub_type： 杂志文章
doi：
更新日期：1992-07-01 00:00:00
abstract：:Approximately 80% of breast cancers express the estrogen receptor-alpha (ERalpha) and are treated with anti-estrogens. Resistance to these agents is a major cause of mortality. We have shown that estrogen inhibits Notch, whereas anti-estrogens or estrogen withdrawal activate Notch signaling. Combined inhibition of Not...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/onc.2009.323
更新日期：2010-01-14 00:00:00
abstract：:Nuclear-enriched RNA-binding proteins (RBPs) are mainly involved in transcriptional regulation, which is a critical checkpoint to tune gene diversity and expression levels. We analyzed nuclear RBPs in human HCC tissues and matched normal control tissues. Based on the gene expression levels, PTBP3 was identified as top...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/s41388-018-0416-8
更新日期：2018-12-01 00:00:00
abstract：:Amplification and overexpression of the E2F3 gene at 6p22 in human bladder cancer is associated with increased tumour stage, grade and proliferation index, and in prostate cancer E2F3 overexpression is linked to tumour aggressiveness. We first used small interfering RNA technology to confirm the potential importance o...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/sj.onc.1209854
更新日期：2007-02-15 00:00:00
