MicroRNAs (miRNAs) are a group of highly conserved small non-coding RNAs that were found to enhance mRNA degradation or inhibit post-transcriptional translation. Accumulating evidence indicates that miRNAs contribute to tumorigenesis and cancer metastasis. microRNA-210 has been largely studied in the past several years and has been identified as a major miRNA induced under hypoxia. A variety of miR-210 targets have been identified pointing to its role, not only in mitochondrial metabolism, but also in angiogenesis, the DNA damage response, cell proliferation, and apoptosis. Based on earlier research findings, this review aims to provide a current overview on the involvement of miRNA-210 in biological processes and diseases.

Energetically speaking, ribosome biogenesis is by far the most costly process of the cell and, therefore, must be highly regulated in order to avoid unnecessary energy expenditure. Not only must ribosomal RNA (rRNA) synthesis, ribosomal protein (RP) transcription, translation, and nuclear import, as well as ribosome assembly, be tightly controlled, these events must be coordinated with other cellular events, such as cell division and differentiation. In addition, ribosome biogenesis must respond rapidly to environmental cues mediated by internal and cell surface receptors, or stress (oxidative stress, DNA damage, amino acid depletion, etc.). This review examines some of the well-studied pathways known to control ribosome biogenesis (PI3K-AKT-mTOR, RB-p53, MYC) and how they may interact with some of the less well studied pathways (eIF2α kinase and RNA editing/splicing) in higher eukaryotes to regulate ribosome biogenesis, assembly, and protein translation in a dynamic manner.

Beyond its possible correlation with stemness of tumor cells, CD133/prominin1 is considered an important marker in breast cancer, since it correlates with tumor size, metastasis and clinical stage of triple-negative breast cancers (TNBC), to date the highest risk breast neoplasia.

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.—Bavelloni, A., Piazzi, M., Faenza, I., Raffini, M., D'Angelo, A., Cattini, L., Cocco, L., Blalock, W. L. Prohibitin 2 represents a novel nuclear AKT substrate during all‐ trans ‐retinoic acid‐induced differentiation of acute promyelocytic leukemia cells. FASEB J . 28, 2009–2019 (2014). www.fasebj.org