MicroRNAs in non-small cell lung cancer: Gene regulation, impact on cancer cellular processes, and therapeutic potential.

Lung cancer remains the most lethal cancer among men and women in the United States and worldwide. The majority of lung cancer cases are classified as non-small cell lung cancer (NSCLC). Developing new therapeutics on the basis of better understanding of NSCLC biology is critical to improve the treatment of NSCLC. MicroRNAs (miRNAs or miRs) are a superfamily of genome-derived, small noncoding RNAs that govern posttranscriptional gene expression in cells. Functional miRNAs are commonly dysregulated in NSCLC, caused by genomic deletion, methylation, or altered processing, which may lead to the changes of many cancer-related pathways and processes, such as growth and death signaling, metabolism, angiogenesis, cell cycle, and epithelial to mesenchymal transition, as well as sensitivity to current therapies. With the understanding of miRNA biology in NSCLC, there are growing interests in developing new therapeutic strategies, namely restoration of tumor suppressive miRNAs and inhibition of tumor promotive miRNAs, to combat against NSCLC. In this article, we provide an overview on the molecular features of NSCLC and current treatment options with a focus on pharmacotherapy and personalized medicine. By illustrating the roles of miRNAs in the control of NSCLC tumorigenesis and progression, we highlight the latest efforts in assessing miRNA-based therapies in animal models and discuss some critical challenges in developing RNA therapeutics

Integrated HI emission in galaxy groups and clusters

The integrated HI emission from hierarchical structures such as groups and clusters of galaxies can be detected by FAST at intermediate redshifts. Here we propose to use FAST to study the evolution of the global HI content of clusters and groups over cosmic time by measuring their integrated HI emissions. We use the Virgo cluster as an example to estimate the detection limit of FAST, and have estimated the integration time to detect a Virgo type cluster at different redshifts (from z=0.1 to z=1.5). We have also employed a semi-analytic model (SAM) to simulate the evolution of HI contents in galaxy clusters. Our simulations suggest that the HI mass of a Virgo-like cluster could be 2-3 times higher and the physical size could be more than 50\% smaller when redshift increases from z=0.3 to z=1. Thus the integration time could be reduced significantly and gas rich clusters at intermediate redshifts can be detected by FAST in less than 2 hour of integration time. For the local universe, we have also used SAM simulations to create mock catalogs of clusters to predict the outcomes from FAST all sky surveys. Comparing with the optically selected catalogs derived by cross matching the galaxy catalogs from the SDSS survey and the ALFALFA survey, we find that the HI mass distribution of the mock catalog with 20 second of integration time agrees well with that of observations. However, the mock catalog with 120 second integration time predicts much more groups and clusters that contains a population of low mass HI galaxies not detected by the ALFALFA survey. Future deep HI blind sky survey with FAST would be able to test such prediction and set constraints to the numerical simulation models. Observational strategy and sample selections for the future FAST observations of galaxy clusters at high redshifts are also discussed.Comment: 18 pages,5 figure

Learners’ Motivation and the Implications for Classroom Teaching

Motivation accounts for remarkable and significant places in individual differences and L2 acquisition. Moreover, its implications for classroom teaching seem to be more practical, which makes a great difference to teachers who can completely understand and take advantage of the implications. Keywords: motivation; classroom teaching Résumé: La motivation joue un rôle remarquable et signifiant dans les différences individuelles et l’acquissions de L2. Pourtant, ses implications pour l’apprentissage en classe apparaissent plus pratiques, ce qui engendre une grande différence dans les enseignants qui peuvent comprendre complètement et en bien profiter. Mots-clés: motivation, apprentissage en classe

Genetically engineered pre-microRNA-34a prodrug suppresses orthotopic osteosarcoma xenograft tumor growth via the induction of apoptosis and cell cycle arrest.

Osteosarcoma (OS) is the most common primary malignant bone tumor in children, and microRNA-34a (miR-34a) replacement therapy represents a new treatment strategy. This study was to define the effectiveness and safety profiles of a novel bioengineered miR-34a prodrug in orthotopic OS xenograft tumor mouse model. Highly purified pre-miR-34a prodrug significantly inhibited the proliferation of human 143B and MG-63 cells in a dose dependent manner and to much greater degrees than controls, which was attributed to induction of apoptosis and G2 cell cycle arrest. Inhibition of OS cell growth and invasion were associated with release of high levels of mature miR-34a from pre-miR-34a prodrug and consequently reduction of protein levels of many miR-34a target genes including SIRT1, BCL2, c-MET, and CDK6. Furthermore, intravenous administration of in vivo-jetPEI formulated miR-34a prodrug significantly reduced OS tumor growth in orthotopic xenograft mouse models. In addition, mouse blood chemistry profiles indicated that therapeutic doses of bioengineered miR-34a prodrug were well tolerated in these animals. The results demonstrated that bioengineered miR-34a prodrug was effective to control OS tumor growth which involved the induction of apoptosis and cell cycle arrest, supporting the development of bioengineered RNAs as a novel class of large molecule therapeutic agents