MiR-221 controls CDKN1C/p57 and CDKN1B/p27 expression in human hepatocellular carcinoma.

Abstract:

:The identification of target mRNAs is a key step for assessing the role of aberrantly expressed microRNAs in human cancer. MiR-221 is upregulated in human hepatocellular carcinoma (HCC) as well as in other malignancies. One proven target of miR-221 is CDKN1B/p27, whose downregulation affects HCC prognosis. Here, we proved that the cyclin-dependent kinase inhibitor (CDKI) CDKN1C/p57 is also a direct target of miR-221. Indeed, downregulation of both CDKN1B/p27 and CDKN1C/p57 occurs in response to miR-221 transfection into HCC-derived cells and a significant upregulation of both CDKN1B/p27 and CDKN1C/p57 occurs in response to antimiR-221 transfection. A direct interaction of miR-221 with a target site on the 3' UTR of CDKN1C/p57 mRNA was also demonstrated. By controlling these two CDKIs, upregulation of miR-221 can promote growth of HCC cells by increasing the number of cells in S-phase. To assess the relevance of these studies in primary tumors, matched HCC and cirrhosis samples were assayed for miR-221, for CDKN1B/p27 and CDKN1C/p57 expression. MiR-221 was upregulated in 71% of HCCs, whereas CDKN1B/p27 and CDKN1C/p57 proteins were downregulated in 77% of cases. A significant inverse correlation between miR-221 and both CDKN1B/p27 and CDKN1C/p57 was found in HCCs. In conclusion, we suggest that miR-221 has an oncogenic function in hepatocarcinogenesis by targeting CDKN1B/p27 and CDKN1C/p57, hence promoting proliferation by controlling cell-cycle inhibitors. These findings establish a basis toward the development of therapeutic strategies aimed at blocking miR-221 in HCC.

journal_name

Oncogene

journal_title

Oncogene

authors

Fornari F,Gramantieri L,Ferracin M,Veronese A,Sabbioni S,Calin GA,Grazi GL,Giovannini C,Croce CM,Bolondi L,Negrini M

doi

10.1038/onc.2008.178

subject

Has Abstract

pub_date

2008-09-25 00:00:00

pages

5651-61

issue

43

eissn

0950-9232

issn

1476-5594

pii

onc2008178

journal_volume

27

pub_type

杂志文章

相关文献

ONCOGENE文献大全
  • Mouse Neogenin, a DCC-like molecule, has four splice variants and is expressed widely in the adult mouse and during embryogenesis.

    abstract::Neogenin is a member of the N-CAM family of cell adhesion molecules and is closely related to the DCC tumor suppressor gene product. Recently, it has been demonstrated that the DCC/Neogenin subfamily plays a key role in axonal guidance within the embryonic nervous system, however little is known about the function of ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1201225

    authors: Keeling SL,Gad JM,Cooper HM

    更新日期:1997-08-07 00:00:00

  • Characterization of the apoptosis-associated tyrosine kinase (AATYK) expressed in the CNS.

    abstract::We isolated three related cDNA clones from a mouse cerebellar library; the type I cDNA was identical to the gene encoding the apoptosis-associated tyrosine kinase (AATYK), whose expression in myeloid precursor cells is increased during growth arrest or apoptosis. Low levels of AATYK mRNA expression were seen in adult ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1204210

    authors: Tomomura M,Fernandez-Gonzales A,Yano R,Yuzaki M

    更新日期:2001-03-01 00:00:00

  • KATs in cancer: functions and therapies.

    abstract::Post-translational acetylation of lysines is most extensively studied in histones, but this modification is also found in many other proteins and is implicated in a wide range of biological processes in both the cell nucleus and the cytoplasm. Like phosphorylation, acetylation patterns and levels are often altered in ...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:10.1038/onc.2014.453

    authors: Farria A,Li W,Dent SY

    更新日期:2015-09-17 00:00:00

  • Integrin α3β1-CD151 complex regulates dimerization of ErbB2 via RhoA.

    abstract::Integrin α3β1 regulates adhesive interactions of cells with laminins and have a critical role in adhesion-dependent cellular responses. Here, we examined the role of α3β1-integrin in ErbB2-dependent proliferation of breast cancer cells in three-dimensional laminin-rich extracellular matrix (3D lr-ECM). Depletion of α3...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2013.231

    authors: Novitskaya V,Romanska H,Kordek R,Potemski P,Kusińska R,Parsons M,Odintsova E,Berditchevski F

    更新日期:2014-05-22 00:00:00

  • Essential roles of Crk and CrkL in fibroblast structure and motility.

    abstract::Cytosolic proteins containing SH2 and SH3 domains, such as Crk and Crk-like (CrkL), are broadly expressed adapters that interact with a variety of proteins to fulfill key roles in signal transduction pathways triggered by activation of receptor and non-receptor tyrosine kinases. Crk and CrkL are similar to each other ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2013.453

    authors: Park TJ,Curran T

    更新日期:2014-10-23 00:00:00

  • Mammary epithelial-specific expression of the integrin-linked kinase (ILK) results in the induction of mammary gland hyperplasias and tumors in transgenic mice.

    abstract::The integrin linked kinase (ILK) is a cytoplasmic effector of integrin receptors, involved in the regulation of integrin binding properties as well as the activation of cell survival and proliferative pathways, including those involving MAP kinase, PKB/Akt and GSK-3beta. Overexpression of ILK in cultured intestinal an...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1204910

    authors: White DE,Cardiff RD,Dedhar S,Muller WJ

    更新日期:2001-10-25 00:00:00

  • Interaction between HIV-1 Tat and pRb2/p130: a possible mechanism in the pathogenesis of AIDS-related neoplasms.

    abstract::Tat protein is an early nonstructural protein necessary for virus replication, which is secreted by infected cells and taken up by uninfected cells. Extensive evidence indicates that Tat may be a cofactor in the development of AIDS-related neoplasms. The molecular mechanism underlying Tat's oncogenic activity may incl...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1206637

    authors: De Falco G,Bellan C,Lazzi S,Claudio P,La Sala D,Cinti C,Tosi P,Giordano A,Leoncini L

    更新日期:2003-09-18 00:00:00

  • The Ste20-like kinase SLK is required for ErbB2-driven breast cancer cell motility.

    abstract::The Ste20-like kinase, SLK, is involved in the control of cell motility through its effects on actin reorganization and focal adhesion turnover. Here we investigated the role of SLK in chemotaxis downstream of the tyrosine kinase receptor, HER2/ErbB2/Neu, which is frequently overexpressed in human breast cancers. Our ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2009.146

    authors: Roovers K,Wagner S,Storbeck CJ,O'Reilly P,Lo V,Northey JJ,Chmielecki J,Muller WJ,Siegel PM,Sabourin LA

    更新日期:2009-08-06 00:00:00

  • Tumour-suppression function of KLF12 through regulation of anoikis.

    abstract::Suppression of detachment-induced cell death, known as anoikis, is an essential step for cancer metastasis to occur. We report here that expression of KLF12, a member of the Kruppel-like family of transcription factors, is downregulated in lung cancer cell lines that have been selected to grow in the absence of cell a...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2015.394

    authors: Godin-Heymann N,Brabetz S,Murillo MM,Saponaro M,Santos CR,Lobley A,East P,Chakravarty P,Matthews N,Kelly G,Jordan S,Castellano E,Downward J

    更新日期:2016-06-23 00:00:00

  • Characterization of transcription factor E2F complexes during muscle and neuronal differentiation.

    abstract::The activities of E2F transcription factors are inhibited by interactions with members of the retinoblastoma (RB) tumor suppressor family, p105RB, p107 and p130. In cycling cells p107 and p130 also interact with heterodimers comprised of Cdk2 and either A or E cyclins. We characterized E2F complexes present in C2C12 a...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Corbeil HB,Whyte P,Branton PE

    更新日期:1995-09-07 00:00:00

  • Detailed deletion mapping suggests the involvement of a tumor suppressor gene at 17p13.3, distal to p53, in the pathogenesis of lung cancers.

    abstract::The short arm of chromosome 17 is one of the most frequently affected chromosomal regions in lung cancers, while there is solid evidence that the p53 gene at 17p13.1 is a target for frequent 17p deletions. In the present study, we re-evaluated 17p deletions in lung cancers by conducting a detailed analysis of the mini...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1202128

    authors: Konishi H,Takahashi T,Kozaki K,Yatabe Y,Mitsudomi T,Fujii Y,Sugiura T,Matsuda H,Takahashi T,Takahashi T

    更新日期:1998-10-22 00:00:00

  • B23 acts as a nucleolar stress sensor and promotes cell survival through its dynamic interaction with hnRNPU and hnRNPA1.

    abstract::The nucleolus is one of the functional nuclear compartments in which the ribosome biogenesis takes place. Proteomic analysis revealed a large number of nucleolar proteins that are involved in diverse cellular processes, including biogenesis of ribonucleoprotein particles, stress responses, cell proliferation and cell ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2009.473

    authors: Yao Z,Duan S,Hou D,Wang W,Wang G,Liu Y,Wen L,Wu M

    更新日期:2010-03-25 00:00:00

  • STI571 inactivation of the gastrointestinal stromal tumor c-KIT oncoprotein: biological and clinical implications.

    abstract::Mutations in the c-KIT receptor occur somatically in many sporadic Gastrointestinal Stromal Tumors (GIST), and similar mutations have been identified at the germline level in kindreds with multiple GISTs. These mutations activate the tyrosine kinase activity of c-KIT and induce constitutive signaling. To investigate t...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1204704

    authors: Tuveson DA,Willis NA,Jacks T,Griffin JD,Singer S,Fletcher CD,Fletcher JA,Demetri GD

    更新日期:2001-08-16 00:00:00

  • WW domain containing E3 ubiquitin protein ligase 1 targets the full-length ErbB4 for ubiquitin-mediated degradation in breast cancer.

    abstract::ErbB4, a member of the epidermal growth factor receptor family, plays a role in normal breast and breast cancer development by regulating mammary epithelial cell proliferation, survival and differentiation. In this study, we show that WWP1, a C2-WW-HECT type E3 ubiquitin ligase, binds, ubiquitinates and destructs ErbB...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2009.162

    authors: Li Y,Zhou Z,Alimandi M,Chen C

    更新日期:2009-08-20 00:00:00

  • SUMOylation inhibits FOXM1 activity and delays mitotic transition.

    abstract::The forkhead box transcription factor FOXM1 is an essential effector of G2/M-phase transition, mitosis and the DNA damage response. As such, it is frequently deregulated during tumorigenesis. Here we report that FOXM1 is dynamically modified by SUMO1 but not by SUMO2/3 at multiple sites. We show that FOXM1 SUMOylation...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2013.546

    authors: Myatt SS,Kongsema M,Man CW,Kelly DJ,Gomes AR,Khongkow P,Karunarathna U,Zona S,Langer JK,Dunsby CW,Coombes RC,French PM,Brosens JJ,Lam EW

    更新日期:2014-08-21 00:00:00

  • Transcription elongation and eukaryotic gene regulation.

    abstract::Each step in the synthesis of functional transcript by RNA polymerase II provides a level at which gene expression can be regulated. Control over the elongation phase of transcription is a recognized regulatory mechanism in prokaryotes; however, only recently have examples of conditional transcription elongation block...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:

    authors: Spencer CA,Groudine M

    更新日期:1990-06-01 00:00:00

  • Epo regulates erythroid proliferation and differentiation through distinct signaling pathways: implication for erythropoiesis and Friend virus-induced erythroleukemia.

    abstract::We have recently isolated the erythroleukemic cell line, HB60-5, that proliferates in the presence of erythropoietin (Epo) and stem cell factor (SCF), but undergoes terminal differentiation in the presence of Epo alone. Ectopic expression of the ets related transcription factor Fli-1 in these cells resulted in the est...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1203590

    authors: Zochodne B,Truong AH,Stetler K,Higgins RR,Howard J,Dumont D,Berger SA,Ben-David Y

    更新日期:2000-05-04 00:00:00

  • IG20 (MADD splice variant-5), a proapoptotic protein, interacts with DR4/DR5 and enhances TRAIL-induced apoptosis by increasing recruitment of FADD and caspase-8 to the DISC.

    abstract::Recently, we identified Insulinoma-Glucagonoma clone 20 (IG20) that can render cells more susceptible to tumor necrosis factor-alpha (TNF-alpha)-induced apoptosis. In addition, it can slow cell proliferation, and enhance drug- and radiation-induced cell death. TNF-related apoptosis-inducing ligand (TRAIL) can selectiv...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1207804

    authors: Ramaswamy M,Efimova EV,Martinez O,Mulherkar NU,Singh SP,Prabhakar BS

    更新日期:2004-08-12 00:00:00

  • BRCA1 as a potential human prostate tumor suppressor: modulation of proliferation, damage responses and expression of cell regulatory proteins.

    abstract::In addition to breast and ovarian cancer in women, recent evidence suggests that germ-line mutations of the breast cancer susceptibility gene-1 (BRCA1) also confer an increased life-time risk for prostate cancer in male probands. However, it is not known if and how BRCA1 functions in prostate cancer. We stably express...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1202116

    authors: Fan S,Wang JA,Yuan RQ,Ma YX,Meng Q,Erdos MR,Brody LC,Goldberg ID,Rosen EM

    更新日期:1998-06-11 00:00:00

  • Repression of androgen receptor mediated transcription by the ErbB-3 binding protein, Ebp1.

    abstract::Members of the ErbB family of receptors have been implicated in regulation of androgen receptor (AR) activity. Ebp1, an ErbB-3 binding protein recently cloned in our laboratory, possesses an LXXLL motif important in mediating interactions with nuclear hormone receptors. Therefore, we sought to determine if Ebp1 could ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1205638

    authors: Zhang Y,Fondell JD,Wang Q,Xia X,Cheng A,Lu ML,Hamburger AW

    更新日期:2002-08-15 00:00:00

  • MSX2 is an oncogenic downstream target of activated WNT signaling in ovarian endometrioid adenocarcinoma.

    abstract::Ovarian endometrioid adenocarcinomas (OEAs) frequently exhibit constitutive activation of canonical WNT signaling, usually as a result of oncogenic mutations that stabilize and dysregulate the β-catenin protein. In previous work, we used microarray-based methods to compare gene expression in OEAs with and without dysr...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2011.123

    authors: Zhai Y,Iura A,Yeasmin S,Wiese AB,Wu R,Feng Y,Fearon ER,Cho KR

    更新日期:2011-10-06 00:00:00

  • Loss of the Smad3 expression increases susceptibility to tumorigenicity in human gastric cancer.

    abstract::Loss of the tumor suppressive effect of transforming growth factor-beta (TGF-beta) has been commonly found at later stages in carcinogenic progression. Although the genes encoding TGF-beta receptors and Smads have been found genetically altered in certain human cancers, no mutation in Smad3 has been observed. Therefor...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1207259

    authors: Han SU,Kim HT,Seong DH,Kim YS,Park YS,Bang YJ,Yang HK,Kim SJ

    更新日期:2004-02-19 00:00:00

  • Cell context reveals a dual role for Maf in oncogenesis.

    abstract::Maf b-Zip transcription factors are involved in both terminal differentiation and oncogenesis. To investigate this apparent contradiction, we used two different primary cell types and performed an extensive analysis of transformation parameters induced by Maf proteins. We show that MafA and c-Maf are potent oncogenes ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1209171

    authors: Pouponnot C,Sii-Felice K,Hmitou I,Rocques N,Lecoin L,Druillennec S,Felder-Schmittbuhl MP,Eychène A

    更新日期:2006-03-02 00:00:00

  • A novel germline 1.8-kb deletion of hMLH1 mimicking alternative splicing: a founder mutation in the Chinese population.

    abstract::We have previously reported that there is a high incidence of microsatellite instability (MSI) and germline mismatch repair gene mutation in colorectal cancer arising from young Hong Kong Chinese. Most of the germline mutations involve hMSH2, which is different from the mutation spectrum in the Western population. It ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1204376

    authors: Chan TL,Yuen ST,Ho JW,Chan AS,Kwan K,Chung LP,Lam PW,Tse CW,Leung SY

    更新日期:2001-05-24 00:00:00

  • p120, a novel substrate of protein tyrosine kinase receptors and of p60v-src, is related to cadherin-binding factors beta-catenin, plakoglobin and armadillo.

    abstract::A novel protein tyrosine kinase (PTK) substrate, p120, has been previously implicated in ligand-induced signaling through the epidermal growth factor, platelet-derived growth factor and colony-stimulating factor 1 receptors, and in cell transformation by p60v-src. We have isolated a near full-length cDNA encoding muri...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Reynolds AB,Herbert L,Cleveland JL,Berg ST,Gaut JR

    更新日期:1992-12-01 00:00:00

  • Hyperplasia, hyperkeratosis and benign tumor production in transgenic mice by a targeted v-fos oncogene suggest a role for fos in epidermal differentiation and neoplasia.

    abstract::A vector, derived from the human K1 keratin gene, has been employed to target v-fos expression exclusively in the epidermis of transgenic mice. Adult transgenic mice expressors (3-4 months) displayed hyperplasia and hyperkeratosis, initially in wounded (tagged) ears, which later became bilateral. This phenotype appear...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Greenhalgh DA,Rothnagel JA,Wang XJ,Quintanilla MI,Orengo CC,Gagne TA,Bundman DS,Longley MA,Fisher C,Roop DR

    更新日期:1993-08-01 00:00:00

  • TBX2 interacts with heterochromatin protein 1 to recruit a novel repression complex to EGR1-targeted promoters to drive the proliferation of breast cancer cells.

    abstract::Early Growth Response 1 (EGR1) is a stress response transcription factor with multiple tumour suppressor roles in breast tissue, whose expression is often lost in breast cancers. We have previously shown that the breast cancer oncogene TBX2 (T-BOX2) interacts with EGR1 to co-repress EGR1-target genes including the bre...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/s41388-019-0853-z

    authors: Crawford NT,McIntyre AJ,McCormick A,D'Costa ZC,Buckley NE,Mullan PB

    更新日期:2019-08-01 00:00:00

  • Frequent loss of heterozygosity on chromosomes 7 and 9 in benign epithelial ovarian tumours.

    abstract::It is presently unclear if ovarian cancers arise through malignant transformation of pre-existing benign tumours. The apparent rarity of loss of heterozygosity (LOH) reported for benign tumours has led to speculation that they lack malignant potential and represent a biological entity distinct from ovarian carcinoma. ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1201372

    authors: Roy WJ Jr,Watson RH,Hitchcock A,Campbell IG

    更新日期:1997-10-23 00:00:00

  • MLLT3 gene on 9p22 involved in t(9;11) leukemia encodes a serine/proline rich protein homologous to MLLT1 on 19p13.

    abstract::Recently, the MLL gene at 11q23 was found to be involved in a subset of leukemias with an 11q23 abnormality. In the present study, we isolated chimeric cDNAs between the MLL and a gene designated MLLT3 at 9p22 from a cDNA library of an IMS-M1 cell line with a t(9;11)(p22;q23) translocation, a representative karyotypic...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Iida S,Seto M,Yamamoto K,Komatsu H,Tojo A,Asano S,Kamada N,Ariyoshi Y,Takahashi T,Ueda R

    更新日期:1993-11-01 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