16 results on '"Raffini M."'
Search Results
2. Memorie in b/n. Il Piemonte com'era, quando nacque la Regione. Immagini dall'Archivio storico del Consiglio regionale
- Author
-
Grimaldi, Renato and Raffini, M.
- Subjects
trasformazioni culturali ,Piemonte ,trasformazioni sociali ,1970-1980 ,trasformazioni economiche - Published
- 2014
3. Seroprevalence and Microbiological Monitoring in Eggs for Salmonella enterica Serovar Enteritidis and Salmonella enterica Serovar Typhimurium in Ornamental Chicken Flocks in Italy
- Author
-
A Guerrini, G Mescolini, P Roncada, G Tosi, E Raffini, M Frasnelli, and A Guerrini, G Mescolini, P Roncada, G Tosi, E Raffini, M Frasnelli
- Subjects
Serotype ,General Veterinary ,biology ,Backyard poultry ELISA test Foodborne pathogen Italy Salmonella spp. Seroprevalence ,Salmonella enterica ,Ornamental plant ,Seroprevalence ,Flock ,biology.organism_classification ,Salmonella enterica serovar enteritidis ,Microbiology - Abstract
Few data are available about the prevalence of Salmonella enterica serovar Enteritidis (S.E.) and Salmonella enterica serovar Typhimurium (S.T.) in ornamental poultry in Italy. The aim of this study was to investigate the seroprevalence for S.E. and S.T. using serological tests and the prevalence of Salmonella spp. in eggs by culture methods. For this purpose, 240 serum samples and 216 eggs were sampled from asymptomatic and unvaccinated ornamental hens reared in 24 farms, located in 8 different Italian regions. As screening test, a Tube Serum Agglutination test (TSA) was performed on 231 out of 240 serum samples. Four out of 24 farms (16.67%) were serologically positive for Salmonella spp. for a total of 10 samples. These positive samples were confirmed using an ELISA test and the results show that 5/231 (2.16%) and 7/231 (3.03%) serum samples were positive for S.E. and S.T. respectively, and 2/231 (0.87%) for both serotypes. Among all farms, 2/24 (8.33%) were positive for S.E. and 4/24 (16.67%) for S.T. The analysis of eggs using culture methods gave negative results for both yolk and shell pools (0/48, 0.0%). The seroconversion associated with exposure to S.E./S.T. in ornamental poultry, poses a potential public health problem. This study confirms that S.E. and S.T. are widespread in studied backyard poultry farms as asymptomatic form, and animals as potential reservoirs of Salmonella. It is necessary to inform farmers that a regular and periodic control of animals, eggs or meat, is very important to prevention of Salmonella foodborne infections and their spread.
- Published
- 2021
4. Safety profile and impact on survival of tyrosine kinase inhibitors versus conventional therapy in relapse or refractory FLT3 positive acute myeloid leukemia patients
- Author
-
Maria Teresa Bochicchio, Michele Cavo, Sarah Parisi, Carmen Baldazzi, Chiara Sartor, Giovanni Martinelli, Jacopo Nanni, Simone Ragaini, Matteo Olivi, Nicoletta Testoni, Stefano De Polo, Antonio Curti, Maddalena Raffini, Maria Chiara Fontana, Cristina Papayannidis, Emanuela Ottaviani, Francesca Bonifazi, Annalisa Talami, Gianluca Cristiano, Stefania Paolini, Mariachiara Abbenante, Giovanni Marconi, Luca Bertamini, Marconi G., De Polo S., Martinelli G., Nanni J., Bertamini L., Talami A., Olivi M., Ragaini S., Abbenante M.C., Sartor C., Ottaviani E., Bochicchio M.T., Parisi S., Fontana M.C., Cristiano G., Raffini M., Baldazzi C., Testoni N., Bonifazi F., Paolini S., Curti A., Cavo M., and Papayannidis C.
- Subjects
Oncology ,Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Survival ,Adolescent ,medicine.medical_treatment ,Antineoplastic Agents ,Disease ,Disease-Free Survival ,03 medical and health sciences ,0302 clinical medicine ,Refractory ,AML ,Internal medicine ,hemic and lymphatic diseases ,Medicine ,Chemotherapy ,Humans ,Adverse effect ,FLT3 ,Protein Kinase Inhibitors ,Aged ,business.industry ,Surrogate endpoint ,Myeloid leukemia ,Retrospective cohort study ,Hematology ,Middle Aged ,TKI ,respiratory tract diseases ,Survival Rate ,Leukemia, Myeloid, Acute ,fms-Like Tyrosine Kinase 3 ,030220 oncology & carcinogenesis ,Mutation ,Quality of Life ,Neoplastic cell ,Female ,Safety ,business ,030215 immunology - Abstract
Relapsed or refractory (R/R) acute myeloid leukemia (AML) has a poor prognosis, and new therapies are a major clinical need. When mutated, FLT3 drives neoplastic cell proliferation. New drugs (i.e., tyrosine kinase inhibitors, TKIs) showed effectiveness in FLT3-AML and promise to change disease history and outcome. We evaluated the benefit conferred by TKIs in terms of survival, burden of complications and surrogate endpoint of quality of life in a retrospective cohort of 49 FLT3 positive, R/R AML patients. Patients who received TKIs were compared to those treated with conventional chemotherapy. Treatment with TKIs conferred a better OS and wea associated with a lower burden and severity of adverse events. Importantly, patients who received TKIs showed reduced time of hospitalization. In conclusion, treatment with TKI in R/R FLT3-AML was related to a better survival, less and milder AEs, and shorter hospitalization.
- Published
- 2020
5. Identification of Two DNMT3A Mutations Compromising Protein Stability and Methylation Capacity in Acute Myeloid Leukemia
- Author
-
Maddalena Raffini, Samantha Bruno, Maria Chiara Fontana, Martina Pazzaglia, Anna Maria Ferrari, Valentina Robustelli, Simona Soverini, Andrea Ghelli Luserna di Rorà, Maria Teresa Bochicchio, Claudia Venturi, Giovanna Prisinzano, Cristina Papayannidis, Lorenza Bandini, Emanuela Ottaviani, Giovanni Marconi, Eugenia Franchini, Chiara Sartor, Giovanni Martinelli, Maria Chiara Abbenante, Antonella Padella, Giorgia Simonetti, Bruno S., Bochicchio M.T., Franchini E., Padella A., Marconi G., Ghelli Luserna Di Rora A., Venturi C., Raffini M., Prisinzano G., Ferrari A., Bandini L., Robustelli V., Pazzaglia M., Fontana M.C., Sartor C., Abbenante M.C., Papayannidis C., Soverini S., Ottaviani E., Simonetti G., and Martinelli G.
- Subjects
Acute Myeloid Leukemia ,0301 basic medicine ,Genetics ,Article Subject ,business.industry ,Myeloid leukemia ,Methylation ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,lcsh:RC254-282 ,Stop codon ,3. Good health ,Frameshift mutation ,03 medical and health sciences ,Exon ,030104 developmental biology ,0302 clinical medicine ,Oncology ,CpG site ,030220 oncology & carcinogenesis ,DNA methylation ,embryonic structures ,Missense mutation ,Medicine ,business ,Research Article - Abstract
Somatic mutations of DNMT3A occur in about 20% of acute myeloid leukemia (AML) patients. They mostly consist in heterozygous missense mutations targeting a hotspot site at R882 codon, which exhibit a dominant negative effect and are associated with high myeloblast count, advanced age, and poor prognosis. Other types of mutations such as truncations, insertions, or single-nucleotide deletion also affect the DNMT3A gene, though with lower frequency. The present study aimed to characterize two DNMT3A gene mutations identified by next-generation sequencing (NGS), through analysis of protein stability and DNA methylation status at CpG islands. The first mutation was a single-nucleotide variant of DNMT3A at exon 20 causing a premature STOP codon (c.2385G > A; p.Trp795∗; NM_022552.4). The DNMT3A mutation load increased from 4.5% to 38.2% during guadecitabine treatment, with a dominant negative effect on CpG methylation and on protein expression. The second mutation was a novel insertion of 35 nucleotides in exon 22 of DNMT3A (NM_022552.4) that introduced a STOP codon too, after the amino acid Glu863 caused by a frameshift insertion (c.2586_2587insTCATGAATGAGAAAGAGGACATCTTATGGTGCACT; p. Thr862_Glu863fsins). The mutation, which was associated with reduced DNMT3A expression and CpG methylation, persisted at relapse with minor changes in the methylation profile and at protein level. Our data highlight the need to better understand the consequences of DNMT3A mutations other than R882 substitutions in the leukemogenic process in order to tailor patient treatments, thus avoiding therapeutic resistance and disease relapse.
- Published
- 2019
- Full Text
- View/download PDF
6. AKT-dependent phosphorylation of the adenosine deaminases ADAR-1 and -2 inhibits deaminase activity
- Author
-
Lucio Cocco, Irene Faenza, Mirco Raffini, Alberto Bavelloni, Arianna Orsini, Stefano Ratti, Valeriana Cesarini, Angela Gallo, Enrico Focaccia, William L. Blalock, Sara Tomaselli, Manuela Piazzi, Bavelloni A., Focaccia E., Piazzi M., Raffini M., Cesarini V., Tomaselli S., Orsini A., Ratti S., Faenza I., Cocco L., Gallo A., and Blalock W.L.
- Subjects
nucleu ,Adenosine Deaminase ,kinase ,Models, Biological ,Biochemistry ,Substrate Specificity ,protein-protein interaction ,Adenosine deaminase ,Cell Line, Tumor ,RNA EDITING ,Genetics ,medicine ,Protein biosynthesis ,ADAR2 ,Humans ,Phosphorylation ,Molecular Biology ,Protein kinase B ,Cell Nucleus ,Binding Sites ,biology ,Chemistry ,Kinase ,AKT ,RNA-Binding Proteins ,RNA ,Adenosine ,Recombinant Proteins ,Cell biology ,Enzyme Activation ,HEK293 Cells ,Amino Acid Substitution ,oncology ,ADAR ,Mutagenesis, Site-Directed ,biology.protein ,Proto-Oncogene Proteins c-akt ,Biotechnology ,medicine.drug - Abstract
Murine thymoma viral oncogene homolog (AKT) kinases target both cytosolic and nuclear substrates for phosphorylation. Whereas the cytosolic substrates are known to be closely associated with the regulation of apoptosis and autophagy or metabolism and protein synthesis, the nuclear substrates are, for the most part, poorly understood. To better define the role of nuclear AKT, potential AKT substrates were isolated from the nuclear lysates of leukemic cell lines using a phosphorylated AKT substrate antibody and identified in tandem mass spectrometry. Among the proteins identified was adenosine deaminase acting on RNA (ADAR)1p110, the predominant nuclear isoform of the adenosine deaminase acting on double-stranded RNA. Coimmunoprecipitation studies and in vitro kinase assays revealed that AKT-1, -2, and -3 interact with both ADAR1p110 and ADAR2 and phosphorylate these RNA editases. Using site-directed mutagenesis of suspected AKT phosphorylation sites, AKT was found to primarily phosphorylate ADAR1p110 and ADAR2 on T738 and T553, respectively, and overexpression of the phosphomimic mutants ADAR1p110 (T738D) and ADAR2 (T553D) resulted in a 50-100% reduction in editase activity. Thus, activation of AKT has a direct and major impact on RNA editing.-Bavelloni, A., Focaccia, E., Piazzi, M., Raffini, M., Cesarini, V., Tomaselli, S., Orsini, A., Ratti, S., Faenza, I., Cocco, L., Gallo, A., Blalock, W. L. AKT-dependent phosphorylation of the adenosine deaminases ADAR-1 and -2 inhibits deaminase activity.
- Published
- 2019
7. Transcribed ultraconserved region 339 promotes carcinogenesis by modulating tumor suppressor microRNAs
- Author
-
Kishore B. Challagundla, Petra Wise, Patrick Nana-Sinkam, Barbara J. Gitlitz, Ramana V. Davuluri, Han Liang, Maria Angelica Cortez, Shuxing Zhang, Linda Fabris, Hui Ling, Cecilia Fernandez-Cymering, Mariam Murtadha, Massimo Negrini, Leng Han, Lu Chen, Cristina Ivan, Mirco Raffini, Francesca Fanini, Silvia Carloni, Erika Bandini, Giorgia Paliaga, Manuela Ferracin, Meropi Plousiou, Paolo Neviani, Xinna Zhang, Muller Fabbri, Samanta Salvi, Ivan Vannini, George A. Calin, Amelia Cimmino, Melissa Crawford, Zhiyi Guo, Dino Amadori, Ite A. Laird-Offringa, and Vannini I, Wise PM, Challagundla KB, Plousiou M, Raffini M, Bandini E, Fanini F, Paliaga G, Crawford M, Ferracin M, Ivan C, Fabris L, Davuluri RV, Guo Z, Cortez MA, Zhang X, Chen L, Zhang S, Fernandez-Cymering C, Han L, Carloni S, Salvi S, Ling H, Murtadha M, Neviani P, Gitlitz BJ, Laird-Offringa IA, Nana-Sinkam P, Negrini M, Liang H, Amadori D, Cimmino A, Calin GA, Fabbri M.
- Subjects
0301 basic medicine ,Lung Neoplasms ,down -regulation ,Carcinogenesis ,long uncoding RNA, carcinogenesis, lung cancer, overexpression, down -regulation ,General Physics and Astronomy ,Bioinformatics ,medicine.disease_cause ,law.invention ,Mice ,law ,Carcinoma, Non-Small-Cell Lung ,Genes, Tumor Suppressor ,lcsh:Science ,Lung ,Conserved Sequence ,Regulation of gene expression ,Multidisciplinary ,non-coding RNA, microRNA, lung cancer, ultratranscribed regions ,Up-Regulation ,Gene Expression Regulation, Neoplastic ,Female ,RNA, Long Noncoding ,long uncoding RNA ,carcinogenesis ,Science ,Mice, Nude ,Down-Regulation ,Socio-culturale ,Biology ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Downregulation and upregulation ,Cell Line, Tumor ,Cyclins ,microRNA ,medicine ,Animals ,Humans ,Cell Proliferation ,Base Sequence ,RNA ,Cancer ,General Chemistry ,medicine.disease ,Xenograft Model Antitumor Assays ,MicroRNAs ,lung cancer ,030104 developmental biology ,Cyclin E2 ,Cancer research ,Suppressor ,lcsh:Q ,overexpression - Abstract
The transcribed ultraconserved regions (T-UCRs) encode long non-coding RNAs implicated in human carcinogenesis. Their mechanisms of action and the factors regulating their expression in cancers are poorly understood. Here we show that high expression of uc.339 correlates with lower survival in 210 non-small cell lung cancer (NSCLC) patients. We provide evidence from cell lines and primary samples that TP53 directly regulates uc.339. We find that transcribed uc.339 is upregulated in archival NSCLC samples, functioning as a decoy RNA for miR-339-3p, -663b-3p, and -95-5p. As a result, Cyclin E2, a direct target of all these microRNAs is upregulated, promoting cancer growth and migration. Finally, we find that modulation of uc.339 affects microRNA expression. However, overexpression or downregulation of these microRNAs causes no significant variations in uc.339 levels, suggesting a type of interaction for uc.339 that we call “entrapping”. Our results support a key role for uc.339 in lung cancer.
- Published
- 2018
8. Safety profile and impact on survival of tyrosine kinase inhibitors versus conventional therapy in relapse or refractory FLT3 positive acute myeloid leukemia patients.
- Author
-
Marconi G, De Polo S, Martinelli G, Nanni J, Bertamini L, Talami A, Olivi M, Ragaini S, Abbenante MC, Sartor C, Ottaviani E, Bochicchio MT, Parisi S, Fontana MC, Cristiano G, Raffini M, Baldazzi C, Testoni N, Bonifazi F, Paolini S, Curti A, Cavo M, and Papayannidis C
- Subjects
- Adolescent, Adult, Aged, Disease-Free Survival, Female, Humans, Male, Middle Aged, Survival Rate, Antineoplastic Agents administration & dosage, Leukemia, Myeloid, Acute drug therapy, Leukemia, Myeloid, Acute enzymology, Leukemia, Myeloid, Acute genetics, Mutation, Protein Kinase Inhibitors administration & dosage, Quality of Life, fms-Like Tyrosine Kinase 3 antagonists & inhibitors, fms-Like Tyrosine Kinase 3 genetics, fms-Like Tyrosine Kinase 3 metabolism
- Abstract
Relapsed or refractory (R/R) acute myeloid leukemia (AML) has a poor prognosis, and new therapies are a major clinical need. When mutated, FLT3 drives neoplastic cell proliferation. New drugs (i.e., tyrosine kinase inhibitors, TKIs) showed effectiveness in FLT3-AML and promise to change disease history and outcome. We evaluated the benefit conferred by TKIs in terms of survival, burden of complications and surrogate endpoint of quality of life in a retrospective cohort of 49 FLT3 positive, R/R AML patients. Patients who received TKIs were compared to those treated with conventional chemotherapy. Treatment with TKIs conferred a better OS and wea associated with a lower burden and severity of adverse events. Importantly, patients who received TKIs showed reduced time of hospitalization. In conclusion, treatment with TKI in R/R FLT3-AML was related to a better survival, less and milder AEs, and shorter hospitalization., (Copyright © 2020 Elsevier Ltd. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
9. Identification of Two DNMT3A Mutations Compromising Protein Stability and Methylation Capacity in Acute Myeloid Leukemia.
- Author
-
Bruno S, Bochicchio MT, Franchini E, Padella A, Marconi G, Ghelli Luserna di Rorà A, Venturi C, Raffini M, Prisinzano G, Ferrari A, Bandini L, Robustelli V, Pazzaglia M, Fontana MC, Sartor C, Abbenante MC, Papayannidis C, Soverini S, Ottaviani E, Simonetti G, and Martinelli G
- Abstract
Somatic mutations of DNMT3A occur in about 20% of acute myeloid leukemia (AML) patients. They mostly consist in heterozygous missense mutations targeting a hotspot site at R882 codon, which exhibit a dominant negative effect and are associated with high myeloblast count, advanced age, and poor prognosis. Other types of mutations such as truncations, insertions, or single-nucleotide deletion also affect the DNMT3A gene, though with lower frequency. The present study aimed to characterize two DNMT3A gene mutations identified by next-generation sequencing (NGS), through analysis of protein stability and DNA methylation status at CpG islands. The first mutation was a single-nucleotide variant of DNMT3A at exon 20 causing a premature STOP codon (c.2385G > A; p.Trp795
∗ ; NM_022552.4). The DNMT3A mutation load increased from 4.5% to 38.2% during guadecitabine treatment, with a dominant negative effect on CpG methylation and on protein expression. The second mutation was a novel insertion of 35 nucleotides in exon 22 of DNMT3A (NM_022552.4) that introduced a STOP codon too, after the amino acid Glu863 caused by a frameshift insertion (c.2586_2587insTCATGAATGAGAAAGAGGACATCTTATGGTGCACT; p. Thr862_Glu863fsins). The mutation, which was associated with reduced DNMT3A expression and CpG methylation, persisted at relapse with minor changes in the methylation profile and at protein level. Our data highlight the need to better understand the consequences of DNMT3A mutations other than R882 substitutions in the leukemogenic process in order to tailor patient treatments, thus avoiding therapeutic resistance and disease relapse., Competing Interests: Giovanni Martinelli receives compensation as a consultant for ARIAD/INCYTE, Pfizer, Celgene, Amgen, J&J, and Roche. The other authors declare no conflicts of interest., (Copyright © 2019 Samantha Bruno et al.)- Published
- 2019
- Full Text
- View/download PDF
10. AKT-dependent phosphorylation of the adenosine deaminases ADAR-1 and -2 inhibits deaminase activity.
- Author
-
Bavelloni A, Focaccia E, Piazzi M, Raffini M, Cesarini V, Tomaselli S, Orsini A, Ratti S, Faenza I, Cocco L, Gallo A, and Blalock WL
- Subjects
- Adenosine Deaminase chemistry, Adenosine Deaminase genetics, Amino Acid Substitution, Binding Sites genetics, Cell Line, Tumor, Cell Nucleus metabolism, Enzyme Activation, HEK293 Cells, Humans, Models, Biological, Mutagenesis, Site-Directed, Phosphorylation, Proto-Oncogene Proteins c-akt antagonists & inhibitors, RNA Editing, RNA-Binding Proteins chemistry, RNA-Binding Proteins genetics, Recombinant Proteins chemistry, Recombinant Proteins genetics, Recombinant Proteins metabolism, Substrate Specificity, Adenosine Deaminase metabolism, Proto-Oncogene Proteins c-akt metabolism, RNA-Binding Proteins metabolism
- Abstract
Murine thymoma viral oncogene homolog (AKT) kinases target both cytosolic and nuclear substrates for phosphorylation. Whereas the cytosolic substrates are known to be closely associated with the regulation of apoptosis and autophagy or metabolism and protein synthesis, the nuclear substrates are, for the most part, poorly understood. To better define the role of nuclear AKT, potential AKT substrates were isolated from the nuclear lysates of leukemic cell lines using a phosphorylated AKT substrate antibody and identified in tandem mass spectrometry. Among the proteins identified was adenosine deaminase acting on RNA (ADAR)1p110, the predominant nuclear isoform of the adenosine deaminase acting on double-stranded RNA. Coimmunoprecipitation studies and in vitro kinase assays revealed that AKT-1, -2, and -3 interact with both ADAR1p110 and ADAR2 and phosphorylate these RNA editases. Using site-directed mutagenesis of suspected AKT phosphorylation sites, AKT was found to primarily phosphorylate ADAR1p110 and ADAR2 on T738 and T553, respectively, and overexpression of the phosphomimic mutants ADAR1p110 (T738D) and ADAR2 (T553D) resulted in a 50-100% reduction in editase activity. Thus, activation of AKT has a direct and major impact on RNA editing.-Bavelloni, A., Focaccia, E., Piazzi, M., Raffini, M., Cesarini, V., Tomaselli, S., Orsini, A., Ratti, S., Faenza, I., Cocco, L., Gallo, A., Blalock, W. L. AKT-dependent phosphorylation of the adenosine deaminases ADAR-1 and -2 inhibits deaminase activity.
- Published
- 2019
- Full Text
- View/download PDF
11. Publisher Correction: Transcribed ultraconserved region 339 promotes carcinogenesis by modulating tumor suppressor microRNAs.
- Author
-
Vannini I, Wise PM, Challagundla KB, Plousiou M, Raffini M, Bandini E, Fanini F, Paliaga G, Crawford M, Ferracin M, Ivan C, Fabris L, Davuluri RV, Guo Z, Cortez MA, Zhang X, Chen L, Zhang S, Fernandez-Cymering C, Han L, Carloni S, Salvi S, Ling H, Murtadha M, Neviani P, Gitlitz BJ, Laird-Offringa IA, Nana-Sinkam P, Negrini M, Liang H, Amadori D, Cimmino A, Calin GA, and Fabbri M
- Abstract
In the originally published version of this Article, the positions of the final two authors in the author list were inadvertently inverted during the production process. This error has now been corrected in both the PDF and HTML versions of the Article.
- Published
- 2018
- Full Text
- View/download PDF
12. Transcribed ultraconserved region 339 promotes carcinogenesis by modulating tumor suppressor microRNAs.
- Author
-
Vannini I, Wise PM, Challagundla KB, Plousiou M, Raffini M, Bandini E, Fanini F, Paliaga G, Crawford M, Ferracin M, Ivan C, Fabris L, Davuluri RV, Guo Z, Cortez MA, Zhang X, Chen L, Zhang S, Fernandez-Cymering C, Han L, Carloni S, Salvi S, Ling H, Murtadha M, Neviani P, Gitlitz BJ, Laird-Offringa IA, Nana-Sinkam P, Negrini M, Liang H, Amadori D, Cimmino A, Calin GA, and Fabbri M
- Subjects
- Animals, Base Sequence genetics, Carcinogenesis genetics, Carcinoma, Non-Small-Cell Lung pathology, Cell Line, Tumor, Cell Proliferation genetics, Cyclins genetics, Cyclins metabolism, Down-Regulation, Female, Gene Expression Regulation, Neoplastic, Genes, Tumor Suppressor, Humans, Lung pathology, Lung Neoplasms pathology, Mice, Mice, Nude, MicroRNAs metabolism, Up-Regulation, Xenograft Model Antitumor Assays, Carcinoma, Non-Small-Cell Lung genetics, Conserved Sequence genetics, Lung Neoplasms genetics, MicroRNAs genetics, RNA, Long Noncoding metabolism
- Abstract
The transcribed ultraconserved regions (T-UCRs) encode long non-coding RNAs implicated in human carcinogenesis. Their mechanisms of action and the factors regulating their expression in cancers are poorly understood. Here we show that high expression of uc.339 correlates with lower survival in 210 non-small cell lung cancer (NSCLC) patients. We provide evidence from cell lines and primary samples that TP53 directly regulates uc.339. We find that transcribed uc.339 is upregulated in archival NSCLC samples, functioning as a decoy RNA for miR-339-3p, -663b-3p, and -95-5p. As a result, Cyclin E2, a direct target of all these microRNAs is upregulated, promoting cancer growth and migration. Finally, we find that modulation of uc.339 affects microRNA expression. However, overexpression or downregulation of these microRNAs causes no significant variations in uc.339 levels, suggesting a type of interaction for uc.339 that we call "entrapping". Our results support a key role for uc.339 in lung cancer.
- Published
- 2017
- Full Text
- View/download PDF
13. PI-PLCβ1b affects Akt activation, cyclin E expression, and caspase cleavage, promoting cell survival in pro-B-lymphoblastic cells exposed to oxidative stress.
- Author
-
Piazzi M, Blalock WL, Bavelloni A, Faenza I, Raffini M, Tagliavini F, Manzoli L, and Cocco L
- Subjects
- Animals, Apoptosis, Caspase 3 metabolism, Caspase 7 metabolism, Cell Cycle drug effects, Cell Line, Cell Survival, Cyclin A metabolism, Heterocyclic Compounds, 3-Ring pharmacology, Hydrogen Peroxide toxicity, Interleukin-3 metabolism, Mice, Oxidative Stress, Precursor Cells, B-Lymphoid drug effects, Proto-Oncogene Proteins c-akt antagonists & inhibitors, Signal Transduction, Cyclin E metabolism, Phospholipase C beta metabolism, Precursor Cells, B-Lymphoid cytology, Precursor Cells, B-Lymphoid metabolism, Proto-Oncogene Proteins c-akt metabolism
- Abstract
The phosphoinositide-dependent signal transduction pathway has been implicated in the control of a variety of biologic processes, such as the regulation of cellular metabolism and homeostasis, cell proliferation and differentiation, and apoptosis. One of the key players in the regulation of inositol lipid signaling is the phospholipase Cβ1 (PI-PLCβ1), that hydrolyzes phosphatidylinositol 4,5-bisphosphate [PtIns(4,5)P2], giving rise to the second messengers inositol triphosphate and diacylglicerol. PI-PLCβ1 has been associated with the regulation of several cellular functions, some of which have not yet been fully understood. In particular, it has been reported that PI-PLCβ1 protects murine fibroblasts from oxidative stress-induced cell death. The mediators of oxidative stress, reactive oxygen species (ROS), have been shown to regulate major epigenetic processes, causing the silencing of tumor suppressors and enhancing the proliferation of leukemic cells under oxidative stress. Investigation of the interplay between ROS, PI-PLCβ1, and their signaling mediators in leukemia might therefore reveal innovative targets of pharmacological therapy in the treatment for leukemia. In this work, we demonstrate that in pro-B-lymphoblastic cells (Ba/F3), treated with H2O2, PI-PLCβ1b conferred resistance to cell death, promoting cell cycle progression and cell proliferation and influencing the expression of cyclin A and E. Interestingly, we found that, expression of PI-PLCβ1b affects the activity of caspase-3, caspase-7, and of several protein kinases induced by oxidative stress. In particular, PI-PLCβ1b expression completely abolished the phosphorylation of Erk1/2 MAP kinases, down-regulated phosphatase and tensin homolog (PTEN), and up-regulated the phosphorylation of Akt, thereby sustaining cellular proliferation., (© FASEB.)
- Published
- 2015
- Full Text
- View/download PDF
14. Prohibitin 2: At a communications crossroads.
- Author
-
Bavelloni A, Piazzi M, Raffini M, Faenza I, and Blalock WL
- Subjects
- Animals, Gene Expression, Humans, Prohibitins, Protein Binding, Repressor Proteins genetics, Repressor Proteins metabolism, Signal Transduction, Repressor Proteins physiology
- Abstract
Prohibitins (PHBs) are a highly conserved class of proteins first discovered as inhibitors of cellular proliferation. Since then PHBs have been found to have a significant role in transcription, nuclear signaling, mitochondrial structural integrity, cell division, and cellular membrane metabolism, placing these proteins among the key regulators of pathologies such as cancer, neuromuscular degeneration, and other metabolic diseases. The human genome encodes two PHB proteins, prohibitin 1 (PHB1) and prohibitin 2 (PHB2), which function not only as a heterodimeric complex, but also independently. While many previous reviews have focused on the better characterized prohibitin, PHB1, this review focuses on PHB2 and new data concerning its cellular functions both in complex with PHB1 and independent of PHB1., (© 2015 International Union of Biochemistry and Molecular Biology.)
- Published
- 2015
- Full Text
- View/download PDF
15. Identification of the PKR nuclear interactome reveals roles in ribosome biogenesis, mRNA processing and cell division.
- Author
-
Blalock WL, Piazzi M, Bavelloni A, Raffini M, Faenza I, D'Angelo A, and Cocco L
- Subjects
- Active Transport, Cell Nucleus, Cell Cycle Checkpoints, Cell Division, Cell Nucleus metabolism, Gene Expression Regulation, HEK293 Cells, Humans, Proto-Oncogene Mas, RNA, Messenger genetics, Transcriptome, eIF-2 Kinase antagonists & inhibitors, eIF-2 Kinase genetics, RNA, Messenger metabolism, eIF-2 Kinase metabolism
- Abstract
The double-strand RNA-dependent protein kinase, PKR, plays a central role in inflammatory/chronic stress-mediated pathologies such as cancer, diabetes, and neuro/muscular degenerative diseases. Although a significant amount of research has been conducted to elucidate the role of PKR signaling in the cytosol, only recently has attention been paid to the role of PKR in the nuclear compartment. Previously our group reported that phosphorylated forms of PKR are present in the nucleus of acute leukemic cell lines, representing a reservoir of active kinase that responds to stress. Using the CCRF-CEM acute T-cell leukemia cell line, a PKR-specific inhibitor, co-immunoprecipitation and a proteomics approach, which included affinity purified mass spectrometry analysis (AP/MS), we identified the proteins present in active and inactive PKR nuclear complexes. Of the proteins identified in the PKR complexes, sixty-nine (69) were specific to the active complex, while thirty-eight (38) were specific to the inactive complex. An additional thirteen (13) proteins associated specifically with both complexes. The majority of the proteins identified are involved in, ribosome biogenesis, RNA splicing, mRNA stability, gene expression, cell cycle, or chromatin organization, including several with known significance to normal hematopoiesis and/or hematological disease. In agreement with the AP/MS data, basal- or over-expression of PKR under normal growth conditions favored cell proliferation in the tested cell lines, whereas pharmacological inhibition of PKR or shRNA-mediated knock-down did not. PKR was also found to influence the isoform and the level of expression of the proto-oncogene MYC., (© 2013 Wiley Periodicals, Inc.)
- Published
- 2014
- Full Text
- View/download PDF
16. Prohibitin 2 represents a novel nuclear AKT substrate during all-trans retinoic acid-induced differentiation of acute promyelocytic leukemia cells.
- Author
-
Bavelloni A, Piazzi M, Faenza I, Raffini M, D'Angelo A, Cattini L, Cocco L, and Blalock WL
- Subjects
- Apoptosis, Cell Cycle, Cell Nucleus metabolism, Cell Proliferation, Cell Survival, HEK293 Cells, Humans, Mutagenesis, Site-Directed, Oxidative Stress, Phosphorylation, Prohibitins, Proteomics, Signal Transduction, Cell Differentiation, Leukemia, Promyelocytic, Acute metabolism, Proto-Oncogene Proteins c-akt metabolism, Repressor Proteins metabolism, Tretinoin metabolism
- Abstract
The AKT/PKB kinase is essential for cell survival, proliferation, and differentiation; however, aberrant AKT activation leads to the aggressiveness and drug resistance of many human neoplasias. In the human acute promyelocytic leukemia cell line NB4, nuclear AKT activity increases during all-trans retinoic acid (ATRA)-mediated differentiation. As nuclear AKT activity is associated with differentiation, we sought to identify the nuclear substrates of AKT that were phosphorylated after ATRA treatment. A proteomics-based search for nuclear substrates of AKT in ATRA-treated NB4 cells was undertaken by using 2D-electrophoresis/mass spectrometry (MS) in combination with an anti-AKT phospho-substrate antibody. Western blot analysis, an in vitro kinase assay, and/or site-directed mutagenesis were performed to further characterize the MS findings. MS analysis revealed prohibitin (PHB)-2, a multifunctional protein involved in cell cycle progression and the suppression of oxidative stress, to be a putative nuclear substrate of AKT. Follow-up studies confirmed that AKT phosphorylates PHB2 on Ser-91 and that forced expression of the PHB2(S91A) mutant results in a rapid loss of viability and apoptotic cell death. Activation of nuclear AKT during ATRA-mediated differentiation results in the phosphorylation of several proteins, including PHB2, which may serve to coordinate nuclear-mitochondrial events during differentiation.
- Published
- 2014
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.