MiR-17-92 fine-tunes MYC expression and function to ensure optimal B cell lymphoma growth

The synergism between c-MYC and miR-17-19b, a truncated version of the miR-17-92 cluster, is well-documented during tumor initiation. However, little is known about miR-17-19b function in established cancers. Here we investigate the role of miR-17-19b in c-MYC-driven lymphomas by integrating SILAC-based quantitative proteomics, transcriptomics and 3′ untranslated region (UTR) analysis upon miR-17-19b overexpression. We identify over one hundred miR-17-19b targets, of which 40% are co-regulated by c-MYC. Downregulation of a new miR-17/20 target, checkpoint kinase 2 (Chek2), increases the recruitment of HuR to c-MYC transcripts, resulting in the inhibition of c-MYC translation and thus interfering with in vivo tumor growth. Hence, in established lymphomas, miR-17-19b fine-tunes c-MYC activity through a tight control of its function and expression, ultimately ensuring cancer cell homeostasis. Our data highlight the plasticity of miRNA function, reflecting changes in the mRNA landscape and 3' UTR shortening at different stages of tumorigenesis

Ambition at work and career satisfaction: The mediating role of taking charge behavior and the moderating role of pay

Purpose: The purpose of this paper is to examine the moderating role of pay in the relationship between employee ambition and taking charge behavior, and its subsequent effects on employee career satisfaction. Design/methodology/approach: A two-wave quantitative investigation was conducted among alumni of a large public university in the Netherlands. Findings: The results show that taking charge behavior mediates the positive relationship between employee ambition and career satisfaction. They also show that pay positively moderates this mediation, such that the relationship between employee ambition and taking charge behavior is stronger when ambitious employees receive an increase in pay, leading to increased career satisfaction. Conversely, a decrease in pay does not moderate ambitious employees’ taking charge behavior and the impact on their career satisfaction. Research limitations/implications: The study draws on self-report data collected in one country: the Netherlands. Practical implications: The study highlights the importance of pay for higher job involvement, demonstrating its impact on taking charge behavior among employees with higher levels of ambition. Originality/value: This is the first empirical study to examine the impact of pay on employees’ taking charge behavior and the subsequent implications for career satisfaction