Regulatory effect of hsa-miR-5590-3P on TGFβ signaling through targeting of TGFβ-R1, TGFβ-R2, SMAD3 and SMAD4 transcripts.

Abstract:

:Transforming growth factor-β (TGFβ) signaling acts as suppressor and inducer of tumor progression during the early and late stages of cancer, respectively. Some miRNAs have shown a regulatory effect on TGFβ signaling and here, we have used a combination of bioinformatics and experimental tools to show that hsa-miR-5590-3p is a regulator of multiple genes expression in the TGFβ signaling pathway. Consistent with the bioinformatics predictions, hsa-miR-5590-3p had a negative correlation of expression with TGFβ-R1, TGFβ-R2, SMAD3 and SMAD4 genes, detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Then, the dual luciferase assay supported the direct interaction between hsa-miR-5590-3p and TGFβ-R1, TGFβ-R2, SMAD3 and SMAD4-3'UTR sequences. Consistently, the TGFβ-R1 protein level was reduced following the overexpression of hsa-miR-5590-3p, detected by Western analysis. Also, hsa-miR-5590-3p overexpression brought about the downregulation of TGFβ-R1, TGFβ-R2, SMAD3 and SMAD4 expression in HCT-116 cells, detected by RT-qPCR, followed by cell cycle arrest in the sub-G1 phase, detected by flow cytometry. RT-qPCR results indicated that hsa-miR-5590-3p is significantly downregulated in breast tumor tissues (late stage) compared to their normal pairs. Altogether, data introduces hsa-miR-5590-3p as a negative regulator of the TGFβ/SMAD signaling pathway which acts through downregulation of TGFβ-R1, TGFβ-R2, SMAD3 and SMAD4 transcripts. Therefore, it can be tested as a therapy target in cancers in which the TGFβ/SMAD pathway is deregulated.

journal_name

Biol Chem

journal_title

Biological chemistry

authors

Abedini Bakhshmand E,Soltani BM

doi

10.1515/hsz-2018-0264

subject

Has Abstract

pub_date

2019-04-24 00:00:00

pages

677-685

issue

5

eissn

1431-6730

issn

1437-4315

pii

/j/bchm.just-accepted/hsz-2018-0264/hsz-2018-0264.

journal_volume

400

pub_type

杂志文章
  • [18O]-labeled singlet oxygen as a tool for mechanistic studies of 8-oxo-7,8-dihydroguanine oxidative damage: detection of spiroiminodihydantoin, imidazolone and oxazolone derivatives.

    abstract::A water-soluble [18O]-labeled endoperoxide derived from N,N'-di(2,3-dihydroxypropyl)-1,4-naphthalene-dipropanamide (DHPN18O2) has been shown to act as a clean chemical source of [18O]-labeled molecular singlet oxygen. This allows the assessment of the singlet oxygen (1O2) reactivity toward biological targets such as D...

    journal_title:Biological chemistry

    pub_type: 杂志文章

    doi:10.1515/BC.2002.063

    authors: Martinez GR,Medeiros MH,Ravanat JL,Cadet J,Di Mascio P

    更新日期:2002-03-01 00:00:00

  • The production and characterization of artificial heterodimers of the restriction endonuclease EcoRV.

    abstract::A novel approach to studying the inter- and intrasubunit communication required for the activity of homodimeric proteins is described. It was developed for the restriction endonuclease EcoRV, but should also be useful for other homodimeric enzymes. Two ecorV genes encoding different EcoRV mutants are coexpressed in th...

    journal_title:Biological chemistry

    pub_type: 杂志文章

    doi:10.1515/bchm3.1996.377.10.625

    authors: Wende W,Stahl F,Pingoud A

    更新日期:1996-10-01 00:00:00

  • C-terminal peptides of interleukin-6 modulate the expression of junB protooncogene and the production of fibrinogen by HepG2 cells.

    abstract::Interleukin-6 (IL-6) is a 185 amino acid residue helical cytokine with various biological activities (e. g. B cell development, acute phase reaction). We have investigated the role of the 168-185 C-terminal region of IL-6 in the induction of fibrinogen synthesis and expression of junB mRNA using synthetic peptides cor...

    journal_title:Biological chemistry

    pub_type: 杂志文章

    doi:10.1515/BC.2001.079

    authors: Igaz P,Bösze S,Tóth S,Falus A,Hudecz F

    更新日期:2001-04-01 00:00:00

  • Importance of tRNA interactions with 23S rRNA for peptide bond formation on the ribosome: studies with substrate analogs.

    abstract::The major enzymatic activity of the ribosome is the catalysis of peptide bond formation. The active site -- the peptidyl transferase center -- is composed of ribosomal RNA (rRNA), and interactions between rRNA and the reactants, peptidyl-tRNA and aminoacyl-tRNA, are crucial for the reaction to proceed rapidly and effi...

    journal_title:Biological chemistry

    pub_type: 杂志文章,评审

    doi:10.1515/BC.2007.077

    authors: Beringer M,Rodnina MV

    更新日期:2007-07-01 00:00:00

  • Characterization of the specific DNA nicking activity of restriction endonuclease N.BstNBI.

    abstract::N.BstNBI is a unique restriction endonuclease isolated from Bacillus stearothermophilus. We have characterized the recognition sequence and the cleavage site of N.BstNBI. Mapping of cleavage sites of N.BstNBI showed that it recognizes an asymmetric sequence, 5' GAGTC 3', and cleaves only on the top strand 4 base pairs...

    journal_title:Biological chemistry

    pub_type: 杂志文章

    doi:10.1515/BC.2000.137

    authors: Morgan RD,Calvet C,Demeter M,Agra R,Kong H

    更新日期:2000-11-01 00:00:00

  • Substrate specificity of glutaminyl cyclases from plants and animals.

    abstract::Glutaminyl cyclases (QC) catalyze the intramolecular cyclization of N-terminal glutamine residues of peptides and proteins. For a comparison of the substrate specificity of human and papaya QC enzymes, a novel continuous assay was established by adapting an existing discontinuous method. Specificity constants (kcat/Km...

    journal_title:Biological chemistry

    pub_type: 杂志文章

    doi:10.1515/BC.2003.175

    authors: Schilling S,Manhart S,Hoffmann T,Ludwig HH,Wasternack C,Demuth HU

    更新日期:2003-12-01 00:00:00

  • Nitrosative stress and transcription.

    abstract::Low NO concentrations synthesized by constitutively expressed NO synthases act on several signaling pathways activating transcription factors (TF), such as NF-kappaB or AP-1, and thereby influence gene expression. In contrast, during inflammatory reactions the inducible NO synthase produces NO for prolonged periods of...

    journal_title:Biological chemistry

    pub_type: 杂志文章,评审

    doi:10.1515/BC.2003.153

    authors: Kröncke KD

    更新日期:2003-10-01 00:00:00

  • FoxO transcription factors in oxidative stress response and ageing--a new fork on the way to longevity?

    abstract::Forkhead box O (FoxO) transcription factors are important downstream targets of the PI3K/Akt signaling pathway and crucial regulators of cell fate. This function of FoxOs relies on their ability to control diverse cellular functions, including proliferation, differentiation, apoptosis, DNA repair, defense against oxid...

    journal_title:Biological chemistry

    pub_type: 杂志文章,评审

    doi:10.1515/BC.2008.033

    authors: Sedding DG

    更新日期:2008-03-01 00:00:00

  • Evolutionary origins of the mammalian apolipoproteinB RNA editing enzyme, apobec-1: structural homology inferred from analysis of a cloned chicken small intestinal cytidine deaminase.

    abstract::Mammalian apolipoproteinB (apoB) RNA editing is a site-specific deamination reaction that mediates the C to U conversion responsible for apoB48 production in the mammalian small intestine. This process is not detected in chicken apoB RNA. Mammalian apoB RNA editing is mediated by a multicomponent enzyme complex that i...

    journal_title:Biological chemistry

    pub_type: 杂志文章

    doi:10.1515/bchm.1998.379.8-9.1075

    authors: Anant S,Yu H,Davidson NO

    更新日期:1998-08-01 00:00:00

  • Reverse catalysis of elastase from porcine pancreas in frozen aqueous systems.

    abstract::The reverse action of a trypsin-free elastase isolated from porcine pancreas was studied in frozen aqueous systems. Under frozen state conditions, porcine pancreatic elastase was able to catalyse peptide bond formation more effectively than in solution at room temperature. The acceptance of free amino acids as nucleop...

    journal_title:Biological chemistry

    pub_type: 杂志文章

    doi:

    authors: Haensler M,Wehofsky N,Gerisch S,Wissmann JD,Jakubke HD

    更新日期:1998-01-01 00:00:00

  • Structural basis of [NiFe] hydrogenase maturation by Hyp proteins.

    abstract::[NiFe] hydrogenases catalyze reversible hydrogen production/consumption. The active site of [NiFe] hydrogenases contains a complex NiFe(CN)2CO center, and the biosynthesis/maturation of these enzymes is a complex and dynamic process, primarily involving six Hyp proteins (HypABCDEF). HypA and HypB are involved in the N...

    journal_title:Biological chemistry

    pub_type: 杂志文章,评审

    doi:10.1515/hsz-2012-0197

    authors: Watanabe S,Sasaki D,Tominaga T,Miki K

    更新日期:2012-09-08 00:00:00

  • Structural and mechanistic aspects of S-S bonds in the thioredoxin-like family of proteins.

    abstract::Disulfide bonds play a critical role in a variety of structural and mechanistic processes associated with proteins inside the cells and in the extracellular environment. The thioredoxin family of proteins like thioredoxin (Trx), glutaredoxin (Grx) and protein disulfide isomerase, are involved in the formation, transfe...

    journal_title:Biological chemistry

    pub_type: 杂志文章,评审

    doi:10.1515/hsz-2018-0319

    authors: Sousa SF,Neves RPP,Waheed SO,Fernandes PA,Ramos MJ

    更新日期:2019-04-24 00:00:00

  • Multifunctional silica nanoparticles for optical and magnetic resonance imaging.

    abstract::The surface of spherical, nonporous silica nanoparticles (SiO2-NPs) was modified with gadolinium (Gd) complexes, fluorophores, and cell-penetrating peptides to achieve multifunctionality on a single particle. The Gd surface concentrations were 9-16 μmol/g resulting in nanomaterials with high local longitudinal and tra...

    journal_title:Biological chemistry

    pub_type: 杂志文章

    doi:10.1515/hsz-2012-0251

    authors: Joshi R,Feldmann V,Koestner W,Detje C,Gottschalk S,Mayer HA,Sauer MG,Engelmann J

    更新日期:2013-01-01 00:00:00

  • Calcium-sensing receptor: roles in and beyond systemic calcium homeostasis.

    abstract::The cloning of a Ca2+(0)-sensing receptor (CaR) from parathyroid and kidney, coupled with the identification of inherited disorders in Ca2+(0)-sensing resulting from inactivating or activating mutations of this CaR, has provided substantial insights into how Ca2+(0) is regulated at a systemic level. The CaR plays a ce...

    journal_title:Biological chemistry

    pub_type: 杂志文章,评审

    doi:

    authors: Chattopadhyay N,Vassilev PM,Brown EM

    更新日期:1997-08-01 00:00:00

  • Phosphorylase and the origin of reversible protein phosphorylation.

    abstract::This article presents a historical account of the discovery of reversible protein phosphorylation. The process was uncovered in the mid-1950s in a study designed to elucidate the complex hormonal regulation of skeletal muscle glycogen phosphorylase. This enzyme was originally thought to be regulated by AMP now known t...

    journal_title:Biological chemistry

    pub_type: 杂志文章

    doi:10.1515/BC.2010.011

    authors: Fischer EH

    更新日期:2010-02-01 00:00:00

  • Multiplex analysis of mitochondrial DNA pathogenic and polymorphic sequence variants.

    abstract::The mitochondrial DNA (mtDNA) encompasses two classes of functionally important sequence variants: recent pathogenic mutations and ancient adaptive polymorphisms. To rapidly and cheaply evaluate both classes of single nucleotide variants (SNVs), we have developed an integrated system in which mtDNA SNVs are analyzed b...

    journal_title:Biological chemistry

    pub_type: 杂志文章

    doi:10.1515/BC.2010.125

    authors: Poole JC,Procaccio V,Brandon MC,Merrick G,Wallace DC

    更新日期:2010-10-01 00:00:00

  • Redefining proteostasis transcription factors in organismal stress responses, development, metabolism, and health.

    abstract::Eukaryotic organisms have evolved complex and robust cellular stress response pathways to ensure maintenance of proteostasis and survival during fluctuating environmental conditions. Highly conserved stress response pathways can be triggered and coordinated at the cell-autonomous and cell-nonautonomous level by proteo...

    journal_title:Biological chemistry

    pub_type: 杂志文章,评审

    doi:10.1515/hsz-2019-0385

    authors: Jones LM,Chen Y,van Oosten-Hawle P

    更新日期:2020-08-27 00:00:00

  • Pathways of mucin O-glycosylation in normal and malignant rat colonic epithelial cells reveal a mechanism for cancer-associated Sialyl-Tn antigen expression.

    abstract::The Sialyl-Tn antigen (Sialyl alpha-Ser/Thr) is expressed as a cancer-associated antigen on the surface of cancer cells. Its presence is associated with a poor prognosis in patients with colorectal and other cancers. We previously reported that Sialyl-Tn expression in LSC human colon cancer cells could be explained by...

    journal_title:Biological chemistry

    pub_type: 杂志文章

    doi:10.1515/BC.2001.029

    authors: Brockhausen I,Yang J,Lehotay M,Ogata S,Itzkowitz S

    更新日期:2001-02-01 00:00:00

  • A structural network associated with the kallikrein-kinin and renin-angiotensin systems.

    abstract::The kallikrein-kinin and renin-angiotensin (KKS-RAS) systems represent two highly regulated proteolytic systems that are involved in several physiological and pathological processes. Although their protein-protein interactions can be studied using experimental approaches, it is difficult to differentiate between direc...

    journal_title:Biological chemistry

    pub_type: 杂志文章

    doi:10.1515/BC.2010.046

    authors: Stoka V,Turk V

    更新日期:2010-04-01 00:00:00

  • Pyrimidine-2,4,6-Triones: a new effective and selective class of matrix metalloproteinase inhibitors.

    abstract::Matrix metalloproteinases (MMPs) are a family of zinc endopeptidases that have been implicated in various disease processes. Different classes of MMP inhibitors, including hydroxamic acids, phosphinic acids and thiols, have been previously described. Most of these mimic peptides and most likely bind in a similar way t...

    journal_title:Biological chemistry

    pub_type: 杂志文章

    doi:10.1515/BC.2001.159

    authors: Grams F,Brandstetter H,D'Alò S,Geppert D,Krell HW,Leinert H,Livi V,Menta E,Oliva A,Zimmermann G,Gram F,Brandstetter H,D'Alò S,Geppert D,Krell HW,Leinert H,Livi VMenta E,Oliva A,Zimmermann G

    更新日期:2001-08-01 00:00:00

  • Ultraspiracle promotes the nuclear localization of ecdysteroid receptor in mammalian cells.

    abstract::The heterodimer consisting of ecdysteroid receptor (EcR) and ultraspiracle (USP), both of which are members of the nuclear receptor superfamily, is considered to be the functional ecdysteroid receptor. Here we analyzed the subcellular distribution of EcR and USP fused to fluorescent proteins. The experiments were carr...

    journal_title:Biological chemistry

    pub_type: 杂志文章

    doi:10.1515/BC.2005.055

    authors: Nieva C,Gwóźdź T,Dutko-Gwóźdź J,Wiedenmann J,Spindler-Barth M,Wieczorek E,Dobrucki J,Duś D,Henrich V,Ozyhar A,Spindler KD

    更新日期:2005-05-01 00:00:00

  • Characterization of the chicken and rat DCoH gene domains using an improved ligation-mediated PCR method.

    abstract::The bifunctional protein DCoH (dimerization cofactor of HNF-1) is a transcriptional coactivator of homeodomain proteins and a cytoplasmic enzyme. Here we report on the isolation, nucleotide sequence and genomic structure of the chicken and rat DCoH genes. They have an unusual first exon coding for a single amino acid....

    journal_title:Biological chemistry

    pub_type: 杂志文章

    doi:

    authors: Bossow S,Riepl S,Igo-Kemenes T

    更新日期:1998-11-01 00:00:00

  • Kallikrein 6 is a mediator of K-RAS-dependent migration of colon carcinoma cells.

    abstract::Kallikrein 6 (KLK6) is a trypsin-like serine peptidase whose relevance in various types of cancers is currently being explored. Previous studies have shown that KLK6 mRNA is upregulated in colon and gastric cancers; however, the regulatory mechanisms and phenotypic consequences of this upregulation are largely unknown...

    journal_title:Biological chemistry

    pub_type: 杂志文章

    doi:10.1515/BC.2008.087

    authors: Henkhaus RS,Gerner EW,Ignatenko NA

    更新日期:2008-06-01 00:00:00

  • DNA demethylation: turning genes on.

    abstract::The regulation of eukaryotic gene expression is a complicated process involving the interaction of a large number of transacting factors with specific cis-regulatory elements. DNA methylation plays a role in this scheme by acting in cis to modulate protein-DNA interactions. Several lines of evidence indicate that meth...

    journal_title:Biological chemistry

    pub_type: 杂志文章,评审

    doi:10.1515/bchm.1998.379.4-5.401

    authors: Bergman Y,Mostoslavsky R

    更新日期:1998-04-01 00:00:00

  • Evidence for a protective role of the CX3CL1/CX3CR1 axis in a model of amyotrophic lateral sclerosis.

    abstract::Aberrant microglial activation and neuroinflammation is a pathological hallmark of amyotrophic lateral sclerosis (ALS). Fractalkine (CX3CL1) is mostly expressed on neuronal cells. The fractalkine receptor (CX3CR1) is predominantly expressed on microglia. Many progressive neuroinflammatory disorders show disruption of ...

    journal_title:Biological chemistry

    pub_type: 杂志文章

    doi:10.1515/hsz-2018-0204

    authors: Liu C,Hong K,Chen H,Niu Y,Duan W,Liu Y,Ji Y,Deng B,Li Y,Li Z,Wen D,Li C

    更新日期:2019-04-24 00:00:00

  • Calpain function in the differentiation of mesenchymal stem cells.

    abstract::Calpain is a calcium-activated non lysosomal neutral thiol protease (EC 3.4.22.17) present in a wide variety of eukaryotic cells. Calpain is usually present as an inactive form and is activated by calcium ions and phospholipids. The ability of calpain to alter, by limited proteolysis, the activity or function of numer...

    journal_title:Biological chemistry

    pub_type: 杂志文章,评审

    doi:10.1515/BC.2002.079

    authors: Yajima Y,Kawashima S

    更新日期:2002-05-01 00:00:00

  • Evolution of ABC transporters by gene duplication and their role in human disease.

    abstract::The ATP-binding cassette (ABC) transporter genes represent the largest family of transporters and these genes are abundant in the genome of all vertebrates. Through analysis of the genome sequence databases we have characterized the full complement of ABC genes from several mammals and other vertebrates. Multiple gene...

    journal_title:Biological chemistry

    pub_type: 杂志文章,评审

    doi:10.1515/BC.2011.006

    authors: Moitra K,Dean M

    更新日期:2011-01-01 00:00:00

  • Structure and function of bacterial dynamin-like proteins.

    abstract::Membrane dynamics are essential for numerous cellular processes in eukaryotic and prokaryotic cells. In eukaryotic cells, membrane fusion and fission are often catalyzed by large GTPases of the dynamin protein family. These proteins couple GTP hydrolysis to membrane deformation, which eventually leads to fusion or fis...

    journal_title:Biological chemistry

    pub_type: 杂志文章,评审

    doi:10.1515/hsz-2012-0185

    authors: Bramkamp M

    更新日期:2012-11-01 00:00:00

  • A method to determine RNA and DNA oxidation simultaneously by HPLC-ECD: greater RNA than DNA oxidation in rat liver after doxorubicin administration.

    abstract::We developed a novel method for the simultaneous extraction and analysis of total tissue RNA and DNA to quantify the RNA and DNA oxidation products 8-oxo-7,8-dihydroguanosine and 8-oxo-7,8-dihydro-2'-deoxyguanosine using HPLC coupled to electrochemical detection (HPLC-ECD). The protein denaturing agents guanidine thio...

    journal_title:Biological chemistry

    pub_type: 杂志文章

    doi:10.1515/BC.2006.014

    authors: Hofer T,Seo AY,Prudencio M,Leeuwenburgh C

    更新日期:2006-01-01 00:00:00

  • The hyaluronan-binding serine protease from human plasma cleaves HMW and LMW kininogen and releases bradykinin.

    abstract::The influence of the hyaluronan-binding protease (PHBSP), a plasma enzyme with FVII- and pro-urokinase-activating potency, on components of the contact phase (kallikrein/kinin) system was investigated. No activation or cleavage of the proenzymes involved in the contact phase system was observed. The pro-cofactor high ...

    journal_title:Biological chemistry

    pub_type: 杂志文章

    doi:10.1515/BC.2002.184

    authors: Etscheid M,Beer N,Fink E,Seitz R,Johannes D

    更新日期:2002-10-01 00:00:00