Overexpression of microRNA-16 declines cellular growth, proliferation and induces apoptosis in human breast cancer cells

MicroRNAs (miRNA) are a large family of small single-stranded RNA molecules found in all multicellular organisms. Early studies have been shown that miRNA are involved in cancer development and progression, and this role can be done by working as an oncogenes and tumor suppressor genes, so manipulation of this molecules can be a promising approach in cancer therapy, and experimental results represented that the modification in breast cancer phenotype is possible by miRNA expression alteration. miR-16, which is located in 13q14 chromosome, plays critical roles as a tumor suppressor by targeting several oncogenes which regulate cell cycle and apoptosis. Hence, in the present study, we investigated whether miR-16 could decline growth and survival of MCF-7 cell line as model of human breast cancer. MCF-7 cell line was infected with lentiviruses containing miR-16 precursor sequence. The effects of ectopic expression of miR-16 on breast cancer phenotype were examined by cell cycle analysis and apoptosis assays. miR-16 cytotoxicity effect was measured by the MTT assay. We showed that the miR-16 overexpression reduces Cyclin D1 and BCL2 at messenger RNA (mRNA) and protein levels in MCF-7 cell line. In addition, this is found that enforced expression of miR-16 decreases cell growth and proliferation and induces apoptosis in MCF-7 cells. In conclusion, our results revealed that upregulation of miR-16 would be a potential approach for breast cancer therapy. © 2015, The Society for In Vitro Biology

Statistical stability and limit laws for Rovella maps

We consider the family of one-dimensional maps arising from the contracting Lorenz attractors studied by Rovella. Benedicks-Carleson techniques were used by Rovella to prove that there is a one-parameter family of maps whose derivatives along their critical orbits increase exponentially fast and the critical orbits have slow recurrent to the critical point. Metzger proved that these maps have a unique absolutely continuous ergodic invariant probability measure (SRB measure). Here we use the technique developed by Freitas and show that the tail set (the set of points which at a given time have not achieved either the exponential growth of derivative or the slow recurrence) decays exponentially fast as time passes. As a consequence, we obtain the continuous variation of the densities of the SRB measures and associated metric entropies with the parameter. Our main result also implies some statistical properties for these maps.Comment: 1 figur

MicroRNA-129-1 acts as tumour suppressor and induces cell cycle arrest of GBM cancer cells through targeting IGF2BP3 and MAPK1

Background MicroRNA-129-1 (miR-129-1) seems to behave as a tumour suppressor since its decreased expression is associated with different tumours such as glioblastoma multiforme (GBM). GBM is the most common form of brain tumours originating from glial cells. The impact of miR-129-1 downregulation on GBM pathogenesis has yet to be elucidated. Methods MiR-129-1 was overexpressed in GBM cells, and its effect on proliferation was investigated by cell cycle assay. MiR-129-1 predicted targets (CDK6, IGF1, HDAC2, IGF2BP3 and MAPK1) were also evaluated by western blot and luciferase assay. Results Restoration of miR-129-1 reduced cell proliferation and induced G1 accumulation, significantly. Several functional assays confirmed IGF2BP3, MAPK1 and CDK6 as targets of miR-129-1. Despite the fact that IGF1 expression can be suppressed by miR-129-1, through 30-untranslated region complementary sequence, we could not find any association between IGF1 expression and GBM. MiR-129-1 expression inversely correlates with CDK6, IGF2BP3 and MAPK1 in primary clinical samples. Conclusion This is the first study to propose miR129-1 as a negative regulator of IGF2BP3 and MAPK1 and also a cell cycle arrest inducer in GBM cells. Our data suggests miR-129-1 as a potential tumour suppressor and presents a rationale for the use of miR-129-1 as a novel strategy to improve treatment response in GBM

FILOU oscillation code

The present paper provides a description of the oscillation code FILOU, its main features, type of applications it can be used for, and some representative solutions. The code is actively involved in CoRoT/ESTA exercises (this volume) for the preparation for the proper interpretation of space data from the CoRoT mission. Although CoRoT/ESTA exercises have been limited to the oscillations computations for non-rotating models, the main characteristic of FILOU is, however, the computation of radial and non-radial oscillation frequencies in presence of rotation. In particular, FILOU calculates (in a perturbative approach) adiabatic oscillation frequencies corrected for the effects of rotation (up to the second order in the rotation rate) including near degeneracy effects. Furthermore, FILOU works with either a uniform rotation or a radial differential rotation profile (shellular rotation), feature which makes the code singular in the field.Comment: 6 pages, 5 figures. Astrophysics and Space Science (in press

On the interpretation of echelle diagrams for solar-like oscillations. Effect of centrifugal distortion

This work aims at determining the impact of slow to moderate rotation on the regular patterns often present in solar-like oscillation spectra. We focus on the well-known asteroseismic diagnostic echelle diagrams, examining how rotation may modify the estimates of the large and small spacings, as well as the identification of modes. We illustrate the work with a real case: the solar-like star $\eta$ Bootis. The modeling takes into account rotation effects on the equilibrium models through an effective gravity and on the oscillation frequencies through both perturbative and non-perturbative calculations. We compare the results of both type of calculations in the context of the regular spacings (like the small spacings and the scaled small spacings) and echelle diagrams. We show that for echelle diagrams the perturbative approach remains valid for rotational velocities up to 40-50 km/s. We show that for the rotational velocities measured in solar-like stars, theoretical oscillation frequencies must be corrected up to the second-order in terms of rotation rate, including near degeneracy effects. For rotational velocities of about 16 km/S and higher, diagnostics on large spacings and on modal identification through echelle diagrams can be significantly altered by the presence of the $m\neq0$ components of the rotationally split modes. We found these effects to be detectable in the observed frequency range. Analysis of the effects of rotation on small spacings and scaled small spacings reveals that these can be of the order of, or even larger than surface effects, typically turbulence, microscopic diffusion, etc. Furthermore, we show that scaled spacings are significantly affected by stellar distortion even for small stellar rotational velocities (from 10-15 km/s) and therefore some care must be taken when using them as indicators for probing deep stellar interiors.Comment: 10 pages,5 figures, accepted for publication in ApJ; http://iopscience.iop.org/0004-637X/721/1/537

Gravity modes in rapidly rotating stars. Limits of perturbative methods

CoRoT and Kepler missions are now providing high-quality asteroseismic data for a large number of stars. Among intermediate-mass and massive stars, fast rotators are common objects. Taking the rotation effects into account is needed to correctly understand, identify, and interpret the observed oscillation frequencies of these stars. A classical approach is to consider the rotation as a perturbation. In this paper, we focus on gravity modes, such as those occurring in gamma Doradus, slowly pulsating B (SPB), or Be stars. We aim to define the suitability of perturbative methods. With the two-dimensional oscillation program (TOP), we performed complete computations of gravity modes -including the Coriolis force, the centrifugal distortion, and compressible effects- in 2-D distorted polytropic models of stars. We started with the modes l=1, n=1-14, and l=2-3, n=1-5,16-20 of a nonrotating star, and followed these modes by increasing the rotation rate up to 70% of the break-up rotation rate. We then derived perturbative coefficients and determined the domains of validity of the perturbative methods. Second-order perturbative methods are suited to computing low-order, low-degree mode frequencies up to rotation speeds ~100 km/s for typical gamma Dor stars or ~150 km/s for B stars. The domains of validity can be extended by a few tens of km/s thanks to the third-order terms. For higher order modes, the domains of validity are noticeably reduced. Moreover, perturbative methods are inefficient for modes with frequencies lower than the Coriolis frequency 2Omega. We interpret this failure as a consequence of a modification in the shape of the resonant cavity that is not taken into account in the perturbative approach.Comment: 8 pages, 6 figures, Astronomy & Astrophysics (in press

A theoretical approach for the interpretation of pulsating PMS intermediate-mass stars

The investigation of the pulsation properties of pre-main-sequence intermediate-mass stars is a promising tool to evaluate the intrinsic properties of these stars and to constrain current evolutionary models. Many new candidates of this class have been discovered during the last decade and very accurate data are expected from space observations obtained for example with the CoRoT satellite. In this context we aim at developing a theoretical approach for the interpretation of observed frequencies, both from the already available ground-based observations and from the future more accurate and extensive CoRoT results. To this purpose we have started a project devoted to the computations of fine and extensive grids of asteroseismic models of intermediate mass pre-main-sequence stars. The obtained frequencies are used to derive an analytical relation between the large frequency separation and the stellar luminosity and effective temperature and to develop a tool to compare theory and observations in the echelle diagram. The predictive capabilities of the proposed method are verified through the application to two test stars. As a second step, we apply the procedure to two true observations from multisite campaigns and we are able to constrain their stellar parameters, in particular the mass, in spite of the small number of frequencies. We expect that with a significantly higher number of frequencies both the stellar mass and age could be constrained and, at the same time, the physics of the models could be tested.Comment: Accepted for publication on A&