MicroRNA-21 regulates breast cancer invasion partly by targeting tissue inhibitor of metalloproteinase 3 expression

<p>Abstract</p> <p>Background</p> <p>MicroRNAs are non-coding RNA molecules that posttranscriptionally regulate expression of target genes and have been implicated in the progress of cancer proliferation, differentiation and apoptosis. The aim of this study was to determine whether microRNA-21 (miR-21), a specific microRNA implicated in multiple aspects of carcinogenesis, impacts breast cancer invasion by regulating the tissue inhibitor of metalloproteinase 3 (TIMP3) gene.</p> <p>Methods</p> <p>miR-21 expression was investigated in 32 matched breast cancer and normal breast tissues, and in four human breast cancer cell lines, by Taqman quantitative real-time PCR. Cell invasive ability was determined by matrigel invasion assay in vitro, in cells transfected with miR-21 or anti-miR-21 oligonucleotides. In addition, the regulation of tissue inhibitor of metalloproteinase 3 (TIMP3) by miR-21 was evaluated by western blotting and luciferase assays.</p> <p>Results</p> <p>Of the 32 paired samples analyzed, 25 breast cancer tissues displayed overexpression of miR-21 in comparison with matched normal breast epithelium. Additionally, incidence of lymph node metastasis closely correlated with miR-21 expression, suggesting a role for miR-21 in metastasis. Similarly, each of the four breast cancer cell lines analyzed overexpressed miR-21, to varied levels. Further, cells transfected with miR-21 showed significantly increased matrigel invasion compared with control cells, whereas transfection with anti-miR-21 significantly decreased cell invasion. Evaluation of TIMP3 protein levels, a peptidase involved in extarcellular matrix degredation, inversely correlated with miR-21 expression.</p> <p>Conclusion</p> <p>As knockdown of miR-21 increased TIMP3 protein expression and luciferase reporter activity, our data suggests that miR-21 could promote invasion in breast cancer cells via its regulation of TIMP3.</p

Intra-Genomic Ribosomal RNA Polymorphism and Morphological Variation in Elphidium macellum Suggests Inter-Specific Hybridization in Foraminifera

Elphidium macellum is a benthic foraminifer commonly found in the Patagonian fjords. To test whether its highly variable morphotypes are ecophenotypes or different genotypes, we analysed 70 sequences of the SSU rRNA gene from 25 specimens. Unexpectedly, we identified 11 distinct ribotypes, with up to 5 ribotypes co-occurring within the same specimen. The ribotypes differ by varying blocks of sequence located at the end of stem-loop motifs in the three expansion segments specific to foraminifera. These changes, distinct from typical SNPs and indels, directly affect the structure of the expansion segments. Their mosaic distribution suggests that ribotypes originated by recombination of two or more clusters of ribosomal genes. We propose that this expansion segment polymorphism (ESP) could originate from hybridization of morphologically different populations of Patagonian Elphidium. We speculate that the complex geological history of Patagonia enhanced divergence of coastal foraminiferal species and contributed to increasing genetic and morphological variation

Sputtering and ion-induced electron emission of graphite under high-dose nitrogen bombardment

The dependence of the sputtering yield Y and the electron emission coefficient gamma of isotropic graphites (POCO-AXF-5Q and Russian MPG-LT) on ion fluence and ion incidence angle 0 at near room temperatures and the dependence of gamma on target temperature under high dose 30 keV N-2(+) ion irradiation were measured. It was found that Y and gamma are stabilized at fluences F greater than or equal to 1 x 10(19) N/cm(2). A specific target surface topography develops. At steady-state conditions, the N concentration in MPG-LT is 19 at.% and in POCO16 at.%. In the angular range 0 = 0-80degrees, Y and gamma increase and the angular dependence of Y is slightly stronger than that of gamma. Sputtering yields of POCO are 1.5 times higher than those of MPG-LT. The reasons of the difference between the experimental and calculated sputtering yields using the TRIM.SP code are discussed. The dependence of gamma on the target temperature manifests a step-like increase at similar or equal to250 degreesC which may be due to radiation induced structure transformation in the modified surface layer. (C) 2002 Published by Elsevier Science B.V

Energy and temperature dependences of ion-induced electron emission from polycrystalline graphite

The dependences of the yield γ of ion-induced kinetic electron emission from polycrystalline graphite on ion energy E were measured under high-fluence Ar^+ and N^+_2 ion irradiation in energy range 6–30 keV from room temperature to 400 °C. It has been observed that the step-like pattern of temperature dependence γ(T) at the dynamic radiation damage annealing temperature T_a is gradually transformed with decreasing ion energy until γ virtually ceases to depend on temperature. The experimentally obtained energy dependence of the ratio γ(T > T_a)/γ(T < T_a) has been analyzed using the theory of ion-induced kinetic electron emission. Some threshold values of the level of radiation damage v_d measured in dpa under steady state of high-fluence Ar^+ and N^+_2 irradiation have been found. When v becomes less than a threshold value v_d, the graphite lattice is virtually not disordered. It has been found that v_d for Ar^+ ions is greater than v_d for N^+_2 ions

Ion-induced electron emission monitoring of the structure and morphology evolution in HOPG

The temperature dependences of the ion-induced electron emission yield c of highly-oriented pyrolytic graphite (HOPG) under high-fluence (10^(18)–10^(19) ions/cm^2) 30 keV Ar^+ ion irradiation at ion incidence angles from θ = 0° (normal incidence) to 80° have been measured to trace both the structure and morphology changes in the basal oriented samples. The target temperature has been varied during continuous irradiation from T = -180 to 400°C. The surface analysis has been performed by the RHEED and SEM techniques. The surface microgeometry was studied using laser goniophotometry (LGF). The dependences of Υ(T) were found to be strongly non-monotonic and essentially different from the ones for Ar^+ and N_2 ^+ ion irradiation of the polygranular graphites. A sharp peak at irradiation temperature T_p 150°C was found. A strong influence of electron transport anisotropy has been observed, and ion-induced microgeometry is discussed