miR-195b is required for proper cellular homeostasis in the elderly.

Over the last decade we have witnessed an increasing number of studies revealing the functional role of non-coding RNAs in a multitude of biological processes, including cellular homeostasis, proliferation and differentiation. Impaired expression of non-coding RNAs can cause distinct pathological conditions, including herein those affecting the gastrointestinal and cardiorespiratory systems, respectively. miR-15/miR-16/miR-195 family members have been broadly implicated in multiple biological processes, including regulation of cell proliferation, apoptosis and metabolism within distinct tissues, such as heart, liver and lungs. While the functional contribution of miR-195a has been reported in multiple biological contexts, the role of miR-195b remains unexplored. In this study we dissected the functional role of miR-195b by generating CRISPR-Cas9 gene edited miR-195b deficient mice. Our results demonstrate that miR-195b is dispensable for embryonic development. miR-195b-/- mice are fertile and displayed no gross anatomical and/or morphological defects. Mechanistically, cell cycle regulation, metabolism and oxidative stress markers are distinctly impaired in the heart, liver and lungs of aged mice, a condition that is not overtly observed at midlife. The lack of overt functional disarray during embryonic development and early adulthood might be due to temporal and tissue-specific compensatory mechanisms driven by selective upregulation miR-15/miR-16/miR-195 family members. Overall, our data demonstrated that miR-195b is dispensable for embryonic development and adulthood but is required for cellular homeostasis in the elderly.

LncRNA H19 Impairs Chemo and Radiotherapy in Tumorigenesis.

Various treatments based on drug administration and radiotherapy have been devoted to preventing, palliating, and defeating cancer, showing high efficiency against the progression of this disease. Recently, in this process, malignant cells have been found which are capable of triggering specific molecular mechanisms against current treatments, with negative consequences in the prognosis of the disease. It is therefore fundamental to understand the underlying mechanisms, including the genes-and their signaling pathway regulators-involved in the process, in order to fight tumor cells. Long non-coding RNAs, H19 in particular, have been revealed as powerful protective factors in various types of cancer. However, they have also evidenced their oncogenic role in multiple carcinomas, enhancing tumor cell proliferation, migration, and invasion. In this review, we analyze the role of lncRNA H19 impairing chemo and radiotherapy in tumorigenesis, including breast cancer, lung adenocarcinoma, glioma, and colorectal carcinoma.

New Insights into the Roles of lncRNAs as Modulators of Cytoskeleton Architecture and Their Implications in Cellular Homeostasis and in Tumorigenesis.

The importance of the cytoskeleton not only in cell architecture but also as a pivotal element in the transduction of signals that mediate multiple biological processes has recently been highlighted. Broadly, the cytoskeleton consists of three types of structural proteins: (1) actin filaments, involved in establishing and maintaining cell shape and movement; (2) microtubules, necessary to support the different organelles and distribution of chromosomes during cell cycle; and (3) intermediate filaments, which have a mainly structural function showing specificity for the cell type where they are expressed. Interaction between these protein structures is essential for the cytoskeletal mesh to be functional. Furthermore, the cytoskeleton is subject to intense spatio-temporal regulation mediated by the assembly and disassembly of its components. Loss of cytoskeleton homeostasis and integrity of cell focal adhesion are hallmarks of several cancer types. Recently, many reports have pointed out that lncRNAs could be critical mediators in cellular homeostasis controlling dynamic structure and stability of the network formed by cytoskeletal structures, specifically in different types of carcinomas. In this review, we summarize current information available about the roles of lncRNAs as modulators of actin dependent cytoskeleton and their impact on cancer pathogenesis. Finally, we explore other examples of cytoskeletal lncRNAs currently unrelated to tumorigenesis, to illustrate knowledge about them.

The Role of Bmp- and Fgf Signaling Modulating Mouse Proepicardium Cell Fate.

Bmp and Fgf signaling are widely involved in multiple aspects of embryonic development. More recently non coding RNAs, such as microRNAs have also been reported to play essential roles during embryonic development. We have previously demonstrated that microRNAs, i.e., miR-130, play an essential role modulating Bmp and Fgf signaling during early stages of cardiomyogenesis. More recently, we have also demonstrated that microRNAs are capable of modulating cell fate decision during proepicardial/septum transversum (PE/ST) development, since over-expression of miR-23 blocked while miR-125, miR-146, miR-223 and miR-195 enhanced PE/ST-derived cardiomyogenesis, respectively. Importantly, regulation of these microRNAs is distinct modulated by Bmp2 and Fgf2 administration in chicken. In this study, we aim to dissect the functional role of Bmp and Fgf signaling during mouse PE/ST development, their implication regulating post-transcriptional modulators such as microRNAs and their impact on lineage determination. Mouse PE/ST explants and epicardial/endocardial cell cultures were distinctly administrated Bmp and Fgf family members. qPCR analyses of distinct microRNAs, cardiomyogenic, fibrogenic differentiation markers as well as key elements directly epithelial to mesenchymal transition were evaluated. Our data demonstrate that neither Bmp2/Bmp4 nor Fgf2/Fgf8 signaling is capable of inducing cardiomyogenesis, fibrogenesis or inducing EMT in mouse PE/ST explants, yet deregulation of several microRNAs is observed, in contrast to previous findings in chicken PE/ST. RNAseq analyses in mouse PE/ST and embryonic epicardium identified novel Bmp and Fgf family members that might be involved in such cell fate differences, however, their implication on EMT induction and cardiomyogenic and/or fibrogenic differentiation is limited. Thus our data support the notion of species-specific differences regulating PE/ST cardiomyogenic lineage commitment.