Journal ArticleDOI
Specific alterations of the microRNA transcriptome and global network structure in colorectal cancer after treatment with MAPK/ERK inhibitors
Marco Ragusa,Luisa Statello,Marco Maugeri,Alessandra Majorana,Davide Barbagallo,Loredana Salito,Mariangela Sammito,Manuela Santonocito,Rosario Angelica,Andrea Cavallaro,Marina Scalia,Rosario Caltabiano,Giuseppe Privitera,Antonio Biondi,Maria Di Vita,Alessandro Cappellani,E Vasquez,Salvatore Lanzafame,Elisabetta Tendi,Salvatore Celeste,Cinzia Di Pietro,Francesco Basile,Michele Purrello +22 more
TLDR
Results contribute to deepen current knowledge on still uncharacterized features of MAPK/ERK pathway, pinpointing new oncomiRs in CRC and allowing their translation into clinical practice and CRC therapy.Abstract:
The mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway has a master control role in various cancer-related biological processes as cell growth, proliferation, differentiation, migration, and apoptosis. It also regulates many transcription factors that control microRNAs (miRNAs) and their biosynthetic machinery. To investigate on the still poorly characterised global involvement of miRNAs within the pathway, we profiled the expression of 745 miRNAs in three colorectal cancer (CRC) cell lines after blocking the pathway with three different inhibitors. This allowed the identification of two classes of post-treatment differentially expressed (DE) miRNAs: (1) common DE miRNAs in all CRC lines after treatment with a specific inhibitor (class A); (2) DE miRNAs in a single CRC line after treatment with all three inhibitors (class B). By determining the molecular targets, biological roles, network position of chosen miRNAs from class A (miR-372, miR-663b, miR-1226*) and class B (miR-92a-1*, miR-135b*, miR-720), we experimentally demonstrated that they are involved in cell proliferation, migration, apoptosis, and globally affect the regulation circuits centred on MAPK/ERK signaling. Interestingly, the levels of miR-92a-1*, miR-135b*, miR-372, miR-720 are significantly higher in biopsies from CRC patients than in normal controls; they also are significantly higher in CRC patients with mutated KRAS than in those with wild-type genotypes (Wilcoxon test, p < 0.05): the latter could be a downstream effect of ERK pathway overactivation, triggered by KRAS mutations. Finally, our functional data strongly suggest the following miRNA/target pairs: miR-92a-1*/PTEN-SOCS5; miR-135b*/LATS2; miR-372/TXNIP; miR-663b/CCND2. Altogether, these results contribute to deepen current knowledge on still uncharacterized features of MAPK/ERK pathway, pinpointing new oncomiRs in CRC and allowing their translation into clinical practice and CRC therapy.read more
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Identification of Genetic Susceptibility Loci for Colorectal Tumors in a Genome-Wide Meta-analysis
Ulrike Peters,Ulrike Peters,Shuo Jiao,Fredrick R. Schumacher,Carolyn M. Hutter,Carolyn M. Hutter,Aaron K. Aragaki,John A. Baron,Sonja I. Berndt,Stéphane Bézieau,Hermann Brenner,Katja Butterbach,Bette J. Caan,Peter T. Campbell,Christopher S. Carlson,Christopher S. Carlson,Graham Casey,Andrew T. Chan,Jenny Chang-Claude,Stephen J. Chanock,Lin Chen,Gerhard A. Coetzee,Simon G. Coetzee,David V. Conti,Keith R. Curtis,David Duggan,Todd L. Edwards,Charles S. Fuchs,Steven Gallinger,Edward Giovannucci,Stephanie M. Gogarten,Stephen B. Gruber,Robert W. Haile,Tabitha A. Harrison,Richard B. Hayes,Brian E. Henderson,Michael Hoffmeister,John L. Hopper,Thomas J. Hudson,Thomas J. Hudson,David J. Hunter,Rebecca D. Jackson,Sun Ha Jee,Mark A. Jenkins,Wei Hua Jia,Laurence N. Kolonel,Charles Kooperberg,Sébastien Küry,Andrea Z. LaCroix,Cathy C. Laurie,Cecelia A. Laurie,Loic Le Marchand,Mathieu Lemire,David K. Levine,Noralane M. Lindor,Yan Liu,Jing Ma,Karen W. Makar,Keitaro Matsuo,Polly A. Newcomb,Polly A. Newcomb,John D. Potter,John D. Potter,Ross L. Prentice,Conghui Qu,Thomas E. Rohan,Stephanie A. Rosse,Stephanie A. Rosse,Robert E. Schoen,Daniela Seminara,Martha J. Shrubsole,Xiao-Ou Shu,Martha L. Slattery,Darin Taverna,Stephen N. Thibodeau,Cornelia M. Ulrich,Emily White,Emily White,Yong-Bing Xiang,Brent W. Zanke,Yi Xin Zeng,Ben Zhang,Wei Zheng,Li Hsu +83 more
TL;DR: In a large genome-wide association study, polymorphisms close to nucleic acid binding protein 1 (which encodes a DNA-binding protein involved in DNA repair) with colorectal tumor risk and polymorphisms in laminin gamma 1, cyclin D2, and T-box 3 are associated.
Journal ArticleDOI
Pregnancy-associated miRNA-clusters.
Diana M. Morales-Prieto,Stephanie Ospina-Prieto,Wittaya Chaiwangyen,Michael Schoenleben,Udo R. Markert +4 more
TL;DR: This review summarizes current knowledge on the pregnancy-related miRNA clusters - the C19MC, C14MC and miR-371-3 cluster - in regard to pregnancy and also other, mostly pathological circumstances.
Journal ArticleDOI
Potential role of probiotics on colorectal cancer prevention
Mario Uccello,Giulia Malaguarnera,Francesco Basile,Velia D'Agata,Michele Malaguarnera,Gaetano Bertino,Marco Vacante,Filippo Drago,Antonio Biondi +8 more
TL;DR: Several mechanisms could explain the preventive action of probiotics against colorectal cancer onset: alteration of the intestinal microflora; inactivation of cancerogenic compounds; competition with putrefactive and pathogenic microbiota; improvement of the host’s immune response; and inhibition of tyrosine kinase signaling pathways.
Journal ArticleDOI
Molecular characterization of exosomes and their microRNA cargo in human follicular fluid: bioinformatic analysis reveals that exosomal microRNAs control pathways involved in follicular maturation.
Manuela Santonocito,Marilena Vento,Maria Rosa Guglielmino,Rosalia Battaglia,Jessica Wahlgren,Marco Ragusa,Davide Barbagallo,Placido Borzì,Simona Rizzari,Marco Maugeri,Paolo Scollo,Carla Tatone,Hadi Valadi,Michele Purrello,Cinzia Di Pietro +14 more
TL;DR: This study identified a series of exosomal microRNAs that are highly represented in human FF and are involved in follicular maturation and could represent noninvasive biomarkers of oocyte quality in assisted reproductive technology.
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The LATS1 and LATS2 tumor suppressors: beyond the Hippo pathway
Noa Furth,Yael Aylon +1 more
TL;DR: Interestingly, the regulatory networks controlling the mRNA expression pattern of LATS1 and LATS2 differ strongly, and may contribute to the differences in protein binding partners of each kinases and in the subcellular locations in which each kinase exerts its functions.
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