A Curated Database of miRNA Mediated Feed-Forward Loops Involving MYC as Master Regulator

BACKGROUND: The MYC transcription factors are known to be involved in the biology of many human cancer types. But little is known about the Myc/microRNAs cooperation in the regulation of genes at the transcriptional and post-transcriptional level. METHODOLOGY/PRINCIPAL FINDINGS: Employing independent databases with experimentally validated data, we identified several mixed microRNA/Transcription Factor Feed-Forward Loops regulated by Myc and characterized completely by experimentally supported regulatory interactions, in human. We then studied the statistical and functional properties of these circuits and discussed in more detail a few interesting examples involving E2F1, PTEN, RB1 and VEGF. CONCLUSIONS/SIGNIFICANCE: We have assembled and characterized a catalogue of human mixed Transcription Factor/microRNA Feed-Forward Loops, having Myc as master regulator and completely defined by experimentally verified regulatory interactions

Life experiences throughout the ifespan: What do people say (or not) about them?

Life experiences have been a topic of interest for researchers and clinicians for decades. Current knowledge is rooted in two distinct approaches, i.e., personality psychology and psychosomatics. Whereas the first is interested in ordinary life stories of nonclinical individuals, based on a more qualitative, in-depth, and person-driven approach, psychosomatics stresses negative events, mainly in clinical samples, and presents a more quantitative, general, and construct-driven approach. Consequently, available evidence is dispersed and unrelated and many basic questions remain unanswered. This study aimed to explore occurrence, developmental stage, valence, and impact of life experiences and to analyze critical answering patterns (i.e., “I don’t remember,” missingness). Through a cross-sectional retrospective design, 394 adults from the community answered the Lifetime Experiences Scale, which covers 75 life experiences organized in eight domains (i.e., school, job, health, leisure, living conditions, adverse experiences, achievements, and people and relationships). Occurrence of life experiences varied greatly, and the mean number of experiences reported was approximately 30. Regarding developmental stage, most experiences were reported in just one stage—mainly adulthood—however, some could be considered chronic. Globally, life experiences tended to be clearly rated as positive or as negative; additionally, assessed experiences were mainly appraised as positive. Moreover, participants presented their experiences as significant, rating them as high impact. Overall, critical answering patterns were not very expressive: “I don’t remember” and missing answers were below 2 and 5%, respectively, in the majority of experiences. These findings offer several important new insights, suggesting that life experiences are mainly an idiosyncratic topic.This manuscript is part of a doctoral dissertation, which had the support of the Portuguese Foundation for Science and Technology (FCT), through the PhD grant with the reference SFRH/ BD/76022/2011, funded by POPH-QREN-Typology 4.1-Advanced Training, reimbursed by the European Social Fund and national funds from State Budget. This study was conducted at Psychology Research Centre (UID/PSI/01662/2013), University of Minho, and supported by the Portuguese Foundation for Science and Technology and the Portuguese Ministry of Education and Science through national funds and co-financed by FEDER through COMPETE2020 under the PT2020 Partnership Agreement (POCI-01-0145-FEDER-007653).info:eu-repo/semantics/publishedVersio

Myc-regulated microRNAs attenuate embryonic stem cell differentiation

Myc proteins are known to have an important function in stem cell maintenance. As Myc has been shown earlier to regulate microRNAs (miRNAs) involved in proliferation, we sought to determine whether c-Myc also affects embryonic stem (ES) cell maintenance and differentiation through miRNAs. Using a quantitative primer-extension PCR assay we identified miRNAs, including, miR-141, miR-200, and miR-429 whose expression is regulated by c-Myc in ES cells, but not in the differentiated and tumourigenic derivatives of ES cells. Chromatin immunoprecipitation analyses indicate that in ES cells c-Myc binds proximal to genomic regions encoding the induced miRNAs. We used expression profiling and seed homology to identify genes specifically downregulated both by these miRNAs and by c-Myc. We further show that the introduction of c-Myc-induced miRNAs into murine ES cells significantly attenuates the downregulation of pluripotency markers on induction of differentiation after withdrawal of the ES cell maintenance factor LIF. In contrast, knockdown of the endogenous miRNAs accelerate differentiation. Our data show that in ES cells c-Myc acts, in part, through a subset of miRNAs to attenuate differentiation