Cellular senescence and aging: the role of B-MYB

Cellular senescence is a stable cell cycle arrest, caused by insults, such as: telomere erosion, oncogene activation, irradiation, DNA damage, oxidative stress, and viral infection. Extrinsic stimuli such as cell culture stress can also trigger this growth arrest. Senescence is thought to have evolved as an example of antagonistic pleiotropy, as it acts as a tumor suppressor mechanism during the reproductive age, but can promote organismal aging by disrupting tissue renewal, repair, and regeneration later in life. The mechanisms underlying the senescence growth arrest are broadly considered to involve p16(INK4A) -pRB and p53-p21(CIP1/WAF1/SDI1) tumor suppressor pathways; but it is not known what makes the senescence arrest stable and what the critical downstream targets are, as they are likely to be key to the establishment and maintenance of the senescent state. MYB-related protein B (B-MYB/MYBL2), a member of the myeloblastosis family of transcription factors, has recently emerged as a potential candidate for regulating entry into senescence. Here, we review the evidence which indicates that loss of B-MYB expression has an important role in causing senescence growth arrest. We discuss how B-MYB acts, as the gatekeeper, to coordinate transit through the cell cycle, in conjunction with the multivulval class B (MuvB) complex and FOXM1 transcription factors. We also evaluate the evidence connecting B-MYB to the mTOR nutrient signaling pathway and suggest that inhibition of this pathway leading to an extension of healthspan may involve activation of B-MYB

Long non-coding RNA SOX2OT: Expression signature, splicing patterns, and emerging roles in pluripotency and tumorigenesis

SOX2 overlapping transcript (SOX2OT) is a long non-coding RNA which harbors one of the major regulators of pluripotency, SOX2 gene, in its intronic region. SOX2OT gene is mapped to human chromosome 3q26.3 (Chr3q26.3) locus and is extended in a high conserved region of over 700 kb. Little is known about the exact role of SOX2OT; however, recent studies have demonstrated a positive role for it in transcription regulation of SOX2 gene. Similar to SOX2, SOX2OT is highly expressed in embryonic stem cells and down-regulated upon the induction of differentiation. SOX2OT is dynamically regulated during the embryogenesis of vertebrates, and delimited to the brain in adult mice and human. Recently, the disregulation of SOX2OT expression and its concomitant expression with SOX2 have become highlighted in some somatic cancers including esophageal squamous cell carcinoma, lung squamous cell carcinoma, and breast cancer. Interestingly, SOX2OT is differentially spliced into multiple mRNA-like transcripts in stem and cancer cells. In this review, we are describing the structural and functional features of SOX2OT, with an emphasis on its expression signature, its splicing patterns and its critical function in the regulation of SOX2 expression during development and tumorigenesis. © 2015 Shahryari, Saghaeian Jazi, Samaei and Mowla

The Cycle of Risk: Impact of Climate Change on Security Challenges in the Caribbean

The intersection of climate change and security has geopolitical considerations for Caribbean countries and the United States. Addressing climate change through recovery, resilience, and adaptation requires significant financing. In an indebted region, most governments will look elsewhere before agreeing to accept new loans from international financial institutions. Caribbean decision-makers are pragmatic actors, meaning there are opportunities for U.S. counterparts, such as China and Russia, to strengthen diplomatic ties by offering aid or low-interest loans to governments and others on a smaller scale, such as Venezuela and Cuba. Resilient recovery, access to low-interest financing, expansion of the regional security system, and enhancing military-to-military coordination between the United States and the Caribbean would help the region address current and forthcoming challenges.https://digitalcommons.fiu.edu/jgi_research/1045/thumbnail.jp

The effect of microRNA-375 overexpression, an inhibitor of Helicobacter pylori-induced carcinogenesis, on lncRNA SOX2OT

Background: Helicobacter pylori is a major human pathogenic bacterium in gastric mucosa. Although the association between gastric cancer and H. pylori has been well-established, the molecular mechanisms underlying H. pylori-induced carcinogenesis are still under investigation. MicroRNAs (miRNAs) are small noncoding RNAs that modulate gene expression at the posttranscriptional level. Recently, studies have revealed that miRNAs are involved in immune response and host cell response to bacteria. Also, microRNA-375 (miR-375) is a key regulator of epithelial properties that are necessary for securing epithelium-immune system crosstalk. It has been recently reported that miR-375 acts as an inhibitor of H. pylori-induced gastric carcinogenesis. There are few reports on miRNA-mediated targeting long noncoding RNAs (lncRNAs). Objectives: This study aimed to examine the possible effect of miR-375 as an inhibitor of H. pylori-induced carcinogenesis on the expression of lncRNA SOX2 overlapping transcript (SOX2OT) and SOX2, a master regulator of pluripotency of cancer stem cells. Materials and Methods: In a model cell line, NT-2 was transfected with the constructed expression vector pEGFP-C1 contained miR- 375. The RNA isolations and cDNA synthesis were performed after 48 hours of transformation. Expression of miR-375 and SOX2OT and SOX2 were quantified using real-time polymerase chain reaction and compared with control cells transfected with pEGFP-C1-Mock clone. Cell cycle modification was also compared after transfections using the flow cytometry analysis. Results: Following ectopic expression of miR-375, SOX2OT and SOX2 expression analysis revealed a significant decrease in their expression level (P < 0.05) in NT-2 cells compared to the control. Cell cycle analysis following ectopic expression of miR-375 in the NT-2 cells using propidium iodine staining revealed significant extension in sub-G1 cell cycle. Conclusions: This is the first report to show down-regulation of SOX2OT and SOX2 following induced expression of miR-375. This findingmaysuggest expression regulation potential between different classes of ncRNAs, for example between miR-375andSOX2OT. This data not only extends our understanding of possible ncRNA interactions in cancers but also may open novel investigation lines towards elucidation of molecular mechanisms controlling H. pylori inflammation and carcinogenesis. © 2016, Ahvaz Jundishapur University of Medical Sciences

Women\u27s job search behavior in the Egyptian labor market

This study evaluates the difference between male and female job search behavior in the Egyptian labor market and the changes in this behavior between 1998 and 2006, in order to examine the effect of transition toward a market-oriented economy on job search activity. The paper also investigates the determinants of women’s job search behavior. The results reveal three alarming facts that raise worries about women’s labor force participation and their future labor market outcomes: women were less active job searchers than men, the gender gap in job search has widened, and this gap is even wider when excluding registration in government employment offices from the set of job search methods used. Hence, transforming to a market economy has not been accompanied with the necessary transformation in labor market institutions. In a labor market dominated by the private sector, on-the-job search plays a significant role in determining and enhancing labor market outcome

Molecular characterization of XvPer1, a novel antioxidant enzyme from the resurrection plant Xerophyta viscosa, and AC3, a LEA-like protein from Arabidopsis thaliana

By differential screening of a cDNA library of the resurrection plant Xerophyta viscosa, a cDNA termed XvPer I was isolated for its over-expression under dehydration stress. Analysis of the cDNA sequence indicated a hydrophilic protein of a predicted Mw of 24.2 kDa with high identity to plant l-Cys peroxiredoxins, a novel antioxidant enzyme. Southern blot analysis revealed that XvPer I was most probably a single copy gene. The polypeptide sequence had significant identities (-70%) with other recently identified plant I-Cys peroxiredoxins with an absolutely conserved active site (PVCTTE). The protein sequence also had a putative bipartite nuclear localization signal

Identification of new SOX2OT transcript variants highly expressed in human cancer cell lines and down regulated in stem cell differentiation

Long non-coding RNAs are manifested as a new paradigm of molecular effectors in a wide range of human diseases. Human SOX2 overlapping transcript (SOX2OT) gene can generate six lncRNA transcript variants which are functionally assumed to be correlated with cellular differentiation and carcinogenesis. However, the circumstances determining expressional and functional differences between SOX2OT transcript variants remain to be explored. Here, we studied the expression of all SOX2OT transcript variants specifically in five human cancer cell lines by real-time RT-PCR. Changes of the new SOX2OT transcript variants expression were measured during the NT2 teratocarcinoma cell line neuronal-like differentiation and were compared to pluripotency regulators, SOX2 and OCT4A gene expressions. Surprisingly, we identified two new SOX2OT transcripts, named SOX2OT-7, SOX2OT-8 which lack exon 8. We discovered that beside active proximal and distal SOX2OT promoters, different cancer cell lines express high levels of some SOX2OT transcript variants differentially by alternative splicing. Significantly, both SOX2OT-7 and SOX2OT-8 are highly expressed in human cancer cell lines coinciding with SOX2, one of the pluripotency regulators. Our results revealed that SOX2OT-7 is almost the most abundant form of SOX2OT transcript variants in the examined cancer cell lines particularly in NT2 teratocarcinoma cell line where its expression falls upon neuronal-like differentiation similar to SOX2 and OCT4A. We suggest that at least some of SOX2OT transcripts are significantly associated with cancer and stem cell related pathways. © 2015, Springer Science+Business Media Dordrecht

Down-regulatory effects of miR-211 on long non-coding RNA SOX2OT and SOX2 genes in esophageal squamous cell carcinoma

Objective: MicroRNAs (miRNAs) are a class of non-coding RNAs (ncRNAs) that transcriptionally or post-Transcriptionally regulate gene expression through degradation of their mRNA targets and/or translational suppression. However, there are a few reports on miRNA-mediated expression regulation of long ncRNAs (lncRNAs). We have previously reported a significant upregulation of the lncRNA SOX2OT and its intronic coding gene, SOX2, in esophageal squamous cell carcinoma (ESCC) tissue samples. In this study, we aimed to evaluate the effect of induced overexpression of miR-211 on SOX2OT and SOX2 expression in vitro. Materials and Methods: In this experimental study, we performed both bioinformatic and experimental analyses to examine whether these transcripts are regulated by miRNAs. From the list of potential candidate miRNAs, miR-211 was found to have complementary sequences to SOX2OT and SOX2 transcripts. To validate our finding experimentally, we transfected the NT-2 pluripotent cell line (an embryonal carcinoma stem cell) with an expression vector overexpressing miR-211. The expression changes of miR-211, SOX2OT, and SOX2 were then quantified by a real-Time polymerase chain reaction (RT-PCR) approach. Results: Compared with mock-Transfected cells, overexpression of miR-211 caused a significant down-regulation of both genes (P<0.05). Furthermore, flow-cytometry analysis revealed a significant elevation in sub-G1 cell population following ectopic expression of miR-211 in NT-2 cells. Conclusion: We report here, for the first time, the down-regulation of SOX2OT and SOX2 genes by an miRNA. Considering the vital role of SOX2OT and SOX2 genes in pluripotency and tumorigenesis, our data suggest an important and inhibitory role for miR-211 in the aforementioned processes