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[PMID]:29262356
[Au] Autor:Krahn N; Meier M; To V; Booy EP; McEleney K; O'Neil JD; McKenna SA; Patel TR; Stetefeld J
[Ad] Endereço:Department of Chemistry, University of Manitoba, Winnipeg, Manitoba, Canada.
[Ti] Título:Nanoscale Assembly of High-Mobility Group AT-Hook 2 Protein with DNA Replication Fork.
[So] Source:Biophys J;113(12):2609-2620, 2017 Dec 19.
[Is] ISSN:1542-0086
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:High mobility group AT-hook 2 (HMGA2) protein is composed of three AT-hook domains. HMGA2 expresses at high levels in both embryonic stem cells and cancer cells, where it interacts with and stabilizes replication forks (RFs), resulting in elevated cell proliferation rates. In this study, we demonstrated that HMGA2 knockdown reduces cell proliferation. To understand the features required for interaction between HMGA2 and RFs, we studied the solution structure of HMGA2, free and in complex with RFs, using an integrated host of biophysical techniques. Circular dichroism and NMR experiments confirmed the disordered state of unbound HMGA2. Dynamic light scattering and sedimentation velocity experiments demonstrated that HMGA2 and RF are monodisperse in solution, and form an equimolar complex. Small-angle x-ray scattering studies revealed that HMGA2 binds in a side-by-side orientation to RF where 3 AT-hooks act as a clamp to wrap around a distorted RF. Thus, our data provide insights into how HMGA2 interacts with stalled RFs and the function of the process.
[Mh] Termos MeSH primário: Replicação do DNA
DNA/química
DNA/metabolismo
Proteína HMGA2/metabolismo
[Mh] Termos MeSH secundário: Proliferação Celular
DNA/biossíntese
Técnicas de Silenciamento de Genes
Células HEK293
Proteína HMGA2/química
Proteína HMGA2/deficiência
Proteína HMGA2/genética
Seres Humanos
Modelos Moleculares
Conformação de Ácido Nucleico
Ligação Proteica
Conformação Proteica
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (HMGA2 Protein); 9007-49-2 (DNA)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180102
[Lr] Data última revisão:
180102
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171221
[St] Status:MEDLINE


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[PMID]:29025583
[Au] Autor:Lacaria M; El Demellawy D; McGowan-Jordan J
[Ad] Endereço:Genetics Department, Children's Hospital of Eastern Ontario, Ottawa, Canada.
[Ti] Título:A rare case of pediatric lipoma with t(9;12)(p22;q14) and evidence of HMGA2-NFIB gene fusion.
[So] Source:Cancer Genet;216-217:100-104, 2017 Oct.
[Is] ISSN:2210-7762
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Lipoma is a benign tumor, typically of adulthood, with characteristic cytogenetic findings, including rearrangement of 12q13-15; these rearrangements often lead to the fusion of the HMGA2 gene at this locus to the transcriptional regulatory domain of its fusion partner, resulting in neomorphic activity that presumably facilitates the neoplastic process. Herein, we report a rare case of pediatric lipoma with t(9;12)(p22;q14) and evidence of HMGA2-NFIB gene fusion in a 9 year-old boy. This case provides further evidence of the link between NFIB rearrangement and early-onset, deep-seated lipomatous tumors.
[Mh] Termos MeSH primário: Cromossomos Humanos/genética
Proteína HMGA2/genética
Lipoma/genética
Fatores de Transcrição NFI/genética
Proteínas de Fusão Oncogênicas/genética
Translocação Genética
[Mh] Termos MeSH secundário: Adulto
Criança
Pré-Escolar
Seres Humanos
Cariotipagem
Imagem por Ressonância Magnética
Masculino
Meia-Idade
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (HMGA2 Protein); 0 (HMGA2-NFIB fusion protein, human); 0 (NFI Transcription Factors); 0 (Oncogene Proteins, Fusion)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171030
[Lr] Data última revisão:
171030
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171014
[St] Status:MEDLINE


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[PMID]:29025376
[Au] Autor:Li H; Zhao L; Zhang Z; Zhang H; Ding C; Su Z
[Ad] Endereço:1 Department of Thyroid Surgery, Henan Provincial People's Hospital, Zhengzhou, China.
[Ti] Título:Roles of microRNA let-7b in papillary thyroid carcinoma by regulating HMGA2.
[So] Source:Tumour Biol;39(10):1010428317719274, 2017 Oct.
[Is] ISSN:1423-0380
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The incidence of thyroid cancer has increased significantly in the last decade, and the most frequent type of this cancer is papillary thyroid carcinoma. MicroRNAs have been demonstrated to be abnormally expressed in tumors and associated with the development of the tumors. Our aim was to analyze the role and molecular mechanisms of tumor suppressor let-7b in the papillary thyroid carcinoma. Expression of let-7b and high-mobility group A2 in papillary thyroid carcinoma tissues and cell lines was assessed using quantitative reverse transcription polymerase chain reaction and western blot analysis. To explore the role of let-7b or high-mobility group A2 in the BCPAP and TPC-1 cells, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and Transwell methods were used. Let-7b expression was significantly downregulated while expression of high-mobility group A2 was upregulated dramatically in papillary thyroid carcinoma tissues and cells compared with that in normal thyroid tissues and cells. In addition, overexpression of let-7b or knockdown of high-mobility group A2 inhibited cell migration and invasion compared with that of control. Besides, high-mobility group A2 was negatively regulated by let-7b in BCPAP cells. Moreover, high-mobility group A2 reintroduction reversed the anti-proliferation, anti-migration, and anti-invasion roles of let-7b. Let-7b might function as a tumor suppressor in papillary thyroid carcinoma by suppressing the expression of high-mobility group A2, and therefore might provide a promising therapeutic target for patients with papillary thyroid carcinoma.
[Mh] Termos MeSH primário: Carcinoma/genética
Proteína HMGA2/genética
MicroRNAs/genética
Neoplasias da Glândula Tireoide/genética
[Mh] Termos MeSH secundário: Adulto
Idoso
Carcinoma/patologia
Carcinoma Papilar
Linhagem Celular Tumoral
Movimento Celular/genética
Proliferação Celular/genética
Feminino
Regulação Neoplásica da Expressão Gênica
Seres Humanos
Masculino
Meia-Idade
Neoplasias da Glândula Tireoide/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (HMGA2 Protein); 0 (MicroRNAs); 0 (mirnlet7 microRNA, human)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171014
[St] Status:MEDLINE
[do] DOI:10.1177/1010428317719274


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[PMID]:29017393
[Au] Autor:Di Fazio P; Maass M; Roth S; Meyer C; Grups J; Rexin P; Bartsch DK; Kirschbaum A
[Ad] Endereço:1 Department of Visceral, Thoracic and Vascular Surgery, Philipps University of Marburg, Marburg, Germany.
[Ti] Título:Expression of hsa-let-7b-5p, hsa-let-7f-5p, and hsa-miR-222-3p and their putative targets HMGA2 and CDKN1B in typical and atypical carcinoid tumors of the lung.
[So] Source:Tumour Biol;39(10):1010428317728417, 2017 Oct.
[Is] ISSN:1423-0380
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Typical and atypical carcinoid tumors belong to the neuroendocrine lung tumors. They have low recurrence and proliferation rate, lymph node, and distant metastases. Nevertheless, these tumors have shown a more aggressive behavior. In the last years, microRNAs were screened as new tumor markers for their potential diagnostic and therapeutic relevance. The expression of hsa-let-7b-5p, hsa-let-7f-5p, hsa-miR-222-3p, and their targets HMGA2 (high-mobility group A2) and CDKN1B (cyclin-dependent kynase inhibitor 1B, p27 ) was evaluated in this rare small group of patients. We analyzed the clinical data of all typical and atypical carcinoid tumors of patients who underwent surgical operation at Marburg University Hospital (n = 18) from 2000. Quantitative reverse transcription polymerase chain reaction was performed in formalin-fixed paraffin-embedded tumor tissue versus four tumor-free lung tissue samples. HMGA2 was stable or downregulated; only one patient showed a significant overexpression. CDKN1B showed a significant overexpression or a stable level; it was downregulated in two samples only. Hsa-miR-222-3p resulted almost stable or overexpressed except for two samples (significantly downregulated). Hsa-let-7f-5p was stable or overexpressed in the majority of analyzed samples, whereas hsa-let-7b-5p was significantly downregulated. HMGA2 and CDKN1B are differently expressed between atypical and typical carcinoid tumors, thus representing valid biomarkers for the classification of the two tumor groups. Hsa-let-7f-5p and HMGA2 are inversely correlated. Hsa-miR-222-3p does not correlate with its predicted target CDKN1B.
[Mh] Termos MeSH primário: Biomarcadores Tumorais/análise
Tumor Carcinoide/classificação
Tumor Carcinoide/patologia
Neoplasias Pulmonares/classificação
Neoplasias Pulmonares/patologia
[Mh] Termos MeSH secundário: Adulto
Idoso
Inibidor de Quinase Dependente de Ciclina p27/análise
Inibidor de Quinase Dependente de Ciclina p27/biossíntese
Feminino
Proteína HMGA2/análise
Proteína HMGA2/biossíntese
Seres Humanos
Masculino
MicroRNAs/análise
MicroRNAs/biossíntese
Meia-Idade
Reação em Cadeia da Polimerase
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (CDKN1B protein, human); 0 (HMGA2 Protein); 0 (MIRN222 microRNA, human); 0 (MicroRNAs); 0 (mirnlet7 microRNA, human); 147604-94-2 (Cyclin-Dependent Kinase Inhibitor p27)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171017
[Lr] Data última revisão:
171017
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171012
[St] Status:MEDLINE
[do] DOI:10.1177/1010428317728417


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[PMID]:28985345
[Au] Autor:Venkatachalam G; Surana U; Clément MV
[Ad] Endereço:Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore.
[Ti] Título:Replication stress-induced endogenous DNA damage drives cellular senescence induced by a sub-lethal oxidative stress.
[So] Source:Nucleic Acids Res;45(18):10564-10582, 2017 Oct 13.
[Is] ISSN:1362-4962
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Although oxidative stress has been shown to induce senescence and replication stress independently, no study has implicated unresolved replication stress as the driver for cellular senescence in response to oxidative stress. Using cells exposed to increasing concentrations of hydrogen peroxide, we show that sub-lethal amount of exogenous hydrogen peroxide induces two waves of DNA damage. The first wave is rapid and transient while the second wave coincides with the cells transition from the S to the G2/M phases of cell cycle. Subsequently, cells enter growth arrest accompanied by the acquisition of senescence-associated characteristics. Furthermore, a p53-dependent decrease in Rad51, which is associated with the formation of DNA segments with chromatin alterations reinforcing senescence, and Lamin B1 that is involved in chromatin remodeling, is observed during the establishment of the senescent phenotype. On the other hand, increase in senescence associated-ß-Gal activity, a classical marker of senescence and HMGA2, a marker of the senescence-associated heterochromatin foci, is shown to be independent of p53. Together, our findings implicate replication stress-induced endogenous DNA damage as the driver for the establishment of cellular senescence upon sub-lethal oxidative stress, and implicate the role of p53 in some but not all hallmarks of the senescent phenotype.
[Mh] Termos MeSH primário: Senescência Celular/genética
Dano ao DNA
Replicação do DNA
Estresse Oxidativo/genética
[Mh] Termos MeSH secundário: Animais
Linhagem Celular
Quebras de DNA de Cadeia Dupla
Quebras de DNA de Cadeia Simples
Proteína HMGA2/metabolismo
Histonas/metabolismo
Lamina Tipo B/metabolismo
Micronúcleos com Defeito Cromossômico
Rad51 Recombinase/metabolismo
Ratos
Proteína Supressora de Tumor p53/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (HMGA2 Protein); 0 (Histones); 0 (Lamin Type B); 0 (Tumor Suppressor Protein p53); 0 (lamin B1); EC 2.7.7.- (Rad51 Recombinase)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171007
[St] Status:MEDLINE
[do] DOI:10.1093/nar/gkx684


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[PMID]:28968424
[Au] Autor:Mei LL; Wang WJ; Qiu YT; Xie XF; Bai J; Shi ZZ
[Ad] Endereço:Medical School, Kunming University of Science and Technology, Kunming, China.
[Ti] Título:miR-125b-5p functions as a tumor suppressor gene partially by regulating HMGA2 in esophageal squamous cell carcinoma.
[So] Source:PLoS One;12(10):e0185636, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:MicroRNAs (miRNAs) play important roles in the progression of human cancer including esophageal squamous cell carcinoma (ESCC). Although previous reports showed that miR-125b-5p was down-regulated in ESCC, the roles and mechanisms of loss of function of miR-125b-5p in ESCC were still unknown. Using microRNA microarray and GEO datasets, we found and confirmed that miR-125b-5p was down-regulated in ESCC tissues. In-vitro assays showed that ectopic miR-125b-5p expression repressed cell proliferation, migration and invasion, and induced cell senescence. We also found that miR-125b-5p reduced the expressions of cell cycle regulatory genes including CCNA2, CCND1 and CCNE1, and regulated the markers of epithelial to mesenchymal transition (EMT) including E-cadherin, N-cadherin and EMT associated transcription factor Slug, and also decreased the MMPs including MMP2, MMP7 and MMP13. Furthermore, the candidate target gene HMGA2 was negatively regulated by miR-125b-5p both in mRNA and protein levels. Importantly, knockdown of HMGA2 partially phenocopied the effects of miR-125b-5p overexpression on cell cycle regulators and EMT markers. In conclusion, our results suggested that overexpression of miR-125b-5p inhibited cell proliferation, migration and invasion partially by down-regulating HMGA2 in ESCC.
[Mh] Termos MeSH primário: Carcinoma de Células Escamosas/metabolismo
Neoplasias Esofágicas/metabolismo
Genes Supressores de Tumor
Proteína HMGA2/genética
MicroRNAs/genética
[Mh] Termos MeSH secundário: Carcinoma de Células Escamosas/genética
Carcinoma de Células Escamosas/patologia
Ciclo Celular/genética
Linhagem Celular Tumoral
Proliferação Celular
Regulação para Baixo
Transição Epitelial-Mesenquimal/genética
Neoplasias Esofágicas/genética
Neoplasias Esofágicas/patologia
Técnicas de Silenciamento de Genes
Seres Humanos
Invasividade Neoplásica
Metástase Neoplásica
Reação em Cadeia da Polimerase em Tempo Real
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (HMGA2 Protein); 0 (MIRN125 microRNA, human); 0 (MicroRNAs)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171003
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0185636


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[PMID]:28954272
[Au] Autor:Xiao G; Wang X; Yu Y
[Ad] Endereço:Department of General Surgery, Xiangya Hospital, Central South University, Changsha, China.
[Ti] Título:CXCR4/Let-7a Axis Regulates Metastasis and Chemoresistance of Pancreatic Cancer Cells Through Targeting HMGA2.
[So] Source:Cell Physiol Biochem;43(2):840-851, 2017.
[Is] ISSN:1421-9778
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:BACKGROUND/AIMS: Pancreatic cancer cells (PCC) is one of the most risky cancers and gemcitabine (GEM) is the standard first-line drug for treating PCC. The PCC will develop drug resistance to GEM after a period of treatment. However, the detailed molecular mechanism of pathogenesis and drug resistance remains unresolved. METHODS: we employed qRT-PCR and western blot to examine the expression level of CXCR4, let-7a and HMGA2. In addition, we used MTT assay to detect cell proliferation and transwell assay to measure migration and invasiveness. The expression level of epithelial marker E-cadherin and mesenthymal marker N-cadherin was detected by western blot. The apoptosis was determined using annexin V-FITC/PI apoptosis detection kit by flow cytometry. RESULTS: we first proved that CXCR4 negatively regulated let-7a in PCC. Next, let-7a was confirmed to play crucial role in tumorigenesis, metastasis and drug resistance of pancreatic cancer cells Bxpc-3 and Panc-1 in vitro and in vivo. Finally, we identified HMGA2 as important downsteam target of let-7a in PCC and overexpression of HMGA2 restores cell proliferation, metastasis and chemosensitivity of GEM inhibited by let-7a. Conlusion: Taken together, we show an important signaling pathway involved in pathogenesis and drug resistance of PCC, thereby providing deeper insight into molecular mechanism by which CXCR4/let-7a regulates tumorigenesis and drug resistance of PCC. These findings will help us develop new strategies for diagnosis and treatment of PCC.
[Mh] Termos MeSH primário: Antimetabólitos Antineoplásicos/farmacologia
Desoxicitidina/análogos & derivados
Resistência a Medicamentos Antineoplásicos
Proteína HMGA2/genética
Pâncreas/efeitos dos fármacos
Neoplasias Pancreáticas/tratamento farmacológico
Receptores CXCR4/genética
[Mh] Termos MeSH secundário: Animais
Linhagem Celular Tumoral
Desoxicitidina/farmacologia
Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
Proteína HMGA2/análise
Seres Humanos
Camundongos Nus
MicroRNAs/genética
Metástase Neoplásica/genética
Metástase Neoplásica/patologia
Pâncreas/metabolismo
Pâncreas/patologia
Neoplasias Pancreáticas/genética
Neoplasias Pancreáticas/patologia
Receptores CXCR4/análise
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antimetabolites, Antineoplastic); 0 (CXCR4 protein, human); 0 (HMGA2 Protein); 0 (MicroRNAs); 0 (Receptors, CXCR4); 0 (mirnlet7 microRNA, human); 0W860991D6 (Deoxycytidine); B76N6SBZ8R (gemcitabine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170928
[St] Status:MEDLINE
[do] DOI:10.1159/000481610


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[PMID]:28830677
[Au] Autor:Luo H; Li Z; Ge H; Mei D; Zhao L; Jiang L; Geng C; Li Q; Yao X; Cao J
[Ad] Endereço:Department of Occupational and Environmental Health, Dalian Medical University, No. 9 W. Lvshun South Road, Dalian, 116044, China.
[Ti] Título:HMGA2 upregulation mediates Cd-induced migration and invasion in A549 cells and in lung tissues of mice.
[So] Source:Chem Biol Interact;277:1-7, 2017 Nov 01.
[Is] ISSN:1872-7786
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:Cadmium (Cd) is a toxic metal widely found in a number of environmental matrices, and it induces serious adverse effects in various organs and tissues. In this study, the role of high mobility group A2 (HMGA2) in promoting migration and invasion in Cd-treated A549 cells and lung tissues of mice was investigated. Our findings showed that exposure to Cd (2 µM) for 48 h or subcutaneous injection of Cd daily for 6 weeks significantly enhanced the expression of matrix metalloproteinase-9 (MMP-9), matrix metalloproteinase-2 (MMP-2), phosphorylated focal adhesion kinase (p-FAK), and HMGA2 in A549 cells or lung tissues of mice. In A549 cells, HMGA2 knockdown significantly decreased expression of MMP-9, MMP-2 and p-FAK and inhibited the migration and invasion compared to that of only Cd-treated cultures. Overexpression of HMGA2 in HEK-293T cells increased expression of MMP-9, MMP-2 and p-FAK and enhanced the migration and invasion compared with the empty vector transfection group. In conclusion, upregulation of HMGA2 plays an important role in Cd-enhanced migration and invasion. Suppressing HMGA2 expression might have potential values in prevention of Cd-resulted toxicities.
[Mh] Termos MeSH primário: Cádmio/toxicidade
Movimento Celular/efeitos dos fármacos
Poluentes Ambientais/toxicidade
Proteína HMGA2/genética
Pulmão/efeitos dos fármacos
Regulação para Cima/efeitos dos fármacos
[Mh] Termos MeSH secundário: Células A549
Animais
Proteína HMGA2/análise
Seres Humanos
Pulmão/metabolismo
Neoplasias Pulmonares/induzido quimicamente
Neoplasias Pulmonares/genética
Masculino
Metaloproteinase 2 da Matriz/análise
Metaloproteinase 2 da Matriz/genética
Metaloproteinase 9 da Matriz/análise
Metaloproteinase 9 da Matriz/genética
Camundongos
Invasividade Neoplásica/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Environmental Pollutants); 0 (HMGA2 Protein); 00BH33GNGH (Cadmium); EC 3.4.24.24 (Matrix Metalloproteinase 2); EC 3.4.24.35 (Matrix Metalloproteinase 9)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171108
[Lr] Data última revisão:
171108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170824
[St] Status:MEDLINE


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[PMID]:28765279
[Au] Autor:Wang Y; Chen F; Zhao M; Yang Z; Li J; Zhang S; Zhang W; Ye L; Zhang X
[Ad] Endereço:From the State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin 300071, China and.
[Ti] Título:The long noncoding RNA HULC promotes liver cancer by increasing the expression of the HMGA2 oncogene via sequestration of the microRNA-186.
[So] Source:J Biol Chem;292(37):15395-15407, 2017 Sep 15.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The long noncoding RNA highly up-regulated in liver cancer (HULC) is aberrantly elevated in hepatocellular carcinoma (HCC), and this up-regulation is crucial for HCC pathogenesis. However, the underlying mechanism in HULC up-regulation is poorly understood. We hypothesized that HULC might modulate the oncogene high mobility group A2 (HMGA2) to promote hepatocarcinogenesis. Quantitative real-time PCR analysis showed that the expression levels of HULC were positively correlated with those of HMGA2 in clinical HCC tissues. Interestingly, we also observed that HULC could up-regulate HMGA2 in HCC cells. Mechanistically, we found that the microRNA-186 inhibited HMGA2 expression by targeting the 3'-untranslated region (3'-UTR) of HMGA2 mRNA. Strikingly, HULC acted as a competing noncoding RNA to sequester miR-186 and thereby relieved miR-186-mediated HMGA2 repression. Functionally, HMGA2 knockdown decreased the HULC-enhanced growth of HCC cells both and We conclude that the long noncoding RNA HULC increases HMGA2 expression by sequestering miR-186 post-transcriptionally and thereby promotes liver cancer growth, providing new insights into the mechanism by which HULC enhances hepatocarcinogenesis.
[Mh] Termos MeSH primário: Carcinogênese
Carcinoma Hepatocelular/metabolismo
Proteína HMGA2/agonistas
Hepatócitos/metabolismo
MicroRNAs/metabolismo
Modelos Biológicos
RNA Longo não Codificante/metabolismo
[Mh] Termos MeSH secundário: Regiões 3' não Traduzidas
Animais
Carcinoma Hepatocelular/patologia
Linhagem Celular Tumoral
Proliferação Celular
Células HEK293
Proteína HMGA2/genética
Proteína HMGA2/metabolismo
Hepatócitos/patologia
Seres Humanos
Neoplasias Hepáticas/metabolismo
Neoplasias Hepáticas/patologia
Masculino
Camundongos Nus
MicroRNAs/antagonistas & inibidores
Mutação
Transplante de Neoplasias
Interferência de RNA
RNA Longo não Codificante/antagonistas & inibidores
RNA Mensageiro/antagonistas & inibidores
RNA Mensageiro/metabolismo
Proteínas Recombinantes/química
Proteínas Recombinantes/metabolismo
Carga Tumoral
Regulação para Cima
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (3' Untranslated Regions); 0 (HMGA2 Protein); 0 (HULC long non-coding RNA, human); 0 (MIRN186 microRNA, human); 0 (MicroRNAs); 0 (RNA, Long Noncoding); 0 (RNA, Messenger); 0 (Recombinant Proteins)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170927
[Lr] Data última revisão:
170927
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170803
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M117.783738


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[PMID]:28691642
[Au] Autor:Wu WY; Tao SQ; Wang XN; Lobie PE; Wu ZS
[Ad] Endereço:1 Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
[Ti] Título:XIAP 3'-untranslated region serves as a competitor for HMGA2 by arresting endogenous let-7a-5p in human hepatocellular carcinoma.
[So] Source:Tumour Biol;39(7):1010428317719578, 2017 Jul.
[Is] ISSN:1423-0380
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:X-linked inhibitor of apoptosis protein functions as an intrinsic regulator of apoptosis by inhibition of caspase activity and possesses a pivotal role in human cancer development and progression. A growing body of literature has demonstrated that microRNAs lead to the degradation or translational repression of messenger RNAs by binding to the non-coding region of messenger RNA at the 3'-untranslated region. Here, we revealed that the expression of HMGA2 is upregulated with X-linked inhibitor of apoptosis protein after transfection of X-linked inhibitor of apoptosis protein 3'-untranslated region in hepatocellular carcinoma cells, suggesting that X-linked inhibitor of apoptosis protein 3'-untranslated region serves as a competitor for microRNAs and prevent the co-targeted messenger RNA, HMGA2, from being suppressed. We further identified that let-7a-5p could bind to both the X-linked inhibitor of apoptosis protein 3'-untranslated region and HMGA2 3'-untranslated region. Moreover, we demonstrated that the forced expression of X-linked inhibitor of apoptosis protein 3'-untranslated region increases the oncogenicity of hepatocellular carcinoma cells in vitro. Cell functional analyses were performed to examine the association of HMGA2 status and X-linked inhibitor of apoptosis protein 3'-untranslated region. We have also measured the functional readout of let-7a-5p and HMGA2, an assay often employed to provide substantial evidence for the effects of X-linked inhibitor of apoptosis protein 3'-untranslated region on hepatocellular carcinoma cells. In general, our findings suggest that X-linked inhibitor of apoptosis protein 3'-untranslated region serves as a competitive endogenous RNA for HMGA2 to activate hepatocellular carcinoma progression by arresting endogenous let-7a-5p.
[Mh] Termos MeSH primário: Carcinoma Hepatocelular/genética
Proteína HMGA2/genética
Neoplasias Hepáticas/genética
MicroRNAs/genética
Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/genética
[Mh] Termos MeSH secundário: Regiões 3' não Traduzidas
Apoptose/genética
Carcinoma Hepatocelular/patologia
Proliferação Celular
Regulação Neoplásica da Expressão Gênica
Células Hep G2
Seres Humanos
Neoplasias Hepáticas/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (3' Untranslated Regions); 0 (HMGA2 Protein); 0 (MicroRNAs); 0 (X-Linked Inhibitor of Apoptosis Protein); 0 (XIAP protein, human); 0 (mirnlet7 microRNA, human)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170726
[Lr] Data última revisão:
170726
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170711
[St] Status:MEDLINE
[do] DOI:10.1177/1010428317719578



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