Microbial Dysbiosis in Colorectal Cancer (CRC) Patients

The composition of the human intestinal microbiota is linked to health status. The aim was to analyze the microbiota of normal and colon cancer patients in order to establish cancer-related dysbiosis

Siah1 proteins enhance radiosensitivity of human breast cancer cells

<p>Abstract</p> <p>Background</p> <p>Siah proteins play an important role in cancer progression. We evaluated the effect of Siah1, its splice variants Siah1L and the Siah1 mutant with the RING finger deleted (Siah1ΔR) on radiosensitization of human breast cancer cells.</p> <p>Methods</p> <p>The status of Siah1 and Siah1L was analysed in five breast cancer cell lines. To establish stable cells, SKBR3 cells were transfected with Siah1, Siah-1L and Siah1ΔR. Siah1 function was suppressed by siRNA in MCF-7 cells. The impact of Siah1 overexpression and silencing on apoptosis, proliferation, survival, invasion ability and DNA repair was assessed in SKBR3 and MCF-7 cells, also in regards to radiation.</p> <p>Results</p> <p>Siah1 and Siah1L mRNA expression was absent in four of five breast cancer cells lines analysed. Overexpression of Siah1 and Siah1L enhanced radiation-induced apoptosis in stable transfected SKBR3 cells, while Siah1ΔR failed to show this effect. In addition, Siah1 and Siah1L significantly reduced cell clonogenic survival and proliferation. Siah1L sensitization enhancement ratio values were over 1.5 and 4.0 for clonogenic survival and proliferation, respectively, pointing to a highly cooperative and potentially synergistic fashion with radiation. Siah1 or Siah1L significantly reduced invasion ability of SKBR3 and suppressed Tcf/Lef factor activity. Importantly, Siah1 siRNA demonstrated opposite effects in MCF-7 cells. Siah1 and Siah1L overexpression resulted in inhibition of DNA repair as inferred by increased levels of DNA double-strand breaks in irradiated SKBR3 cells.</p> <p>Conclusion</p> <p>Our results reveal for the first time how overexpression of Siah1L and Siah1 can determine radiosensitivity of breast cancer cells. These findings suggest that development of drugs augmenting Siah1 and Siah1L activity could be a novel approach in improving tumor cell kill.</p

miR-135A Regulates Preimplantation Embryo Development through Down-Regulation of E3 Ubiquitin Ligase Seven in Absentia Homolog 1A (SIAH1A) Expression

Background: MicroRNAs (miRNAs) are small non-coding RNA molecules capable of regulating transcription and translation. Previously, a cluster of miRNAs that are specifically expressed in mouse zygotes but not in oocytes or other preimplantation stages embryos are identified by multiplex real-time polymerase chain reaction-based miRNA profiling. The functional role of one of these zygote-specific miRNAs, miR-135a, in preimplantation embryo development was investigated. Methodology/Principal Findings: Microinjection of miR-135a inhibitor suppressed first cell cleavage in more than 30% of the zygotes. Bioinformatics analysis identified E3 Ubiquitin Ligase Seven In Absentia Homolog 1A (Siah1a) as a predicted target of miR-135a. Western blotting and 3′UTR luciferase functional assays demonstrated that miR-135a down-regulated the expression of Siah1 in HeLa cells and in mouse zygotes. Siah1a was expressed in preimplantation embryos and its expression pattern negatively correlated with that of miR-135a. Co-injection of Siah1a-specific antibody with miR-135a inhibitor partially nullified the effect of miR-135a inhibition. Proteasome inhibition by MG-132 revealed that miR-135a regulated proteasomal degradation and potentially controlled the expression of chemokinesin DNA binding protein (Kid). Conclusions/Significance: The present study demonstrated for the first time that zygotic specific miRNA modulates the first cell cleavage through regulating expression of Siah1a. © 2011 Pang et al.published_or_final_versio

Paleomagnetism, magnetic fabric, and Ar-40/Ar-39 dating of Pliocene and Quaternary ignimbrites in the Arequipa area, southern Peru

Ar-40/Ar-39 ages and paleomagnetic correlations using characteristic remanent magnetizations (ChRM) show that two main ignimbrite sheets were deposited at 4.86 +/- 0.07 Ma (La Joya Ignimbrite: LJI) and at 1.63 +/- 0.07 Ma (Arequipa Airport Ignimbrite: AAI) in the Arequipa area, southern Peru. The AAI is a 20-100 m-thick ignimbrite that fills in the Arequipa depression to the west of the city of Arequipa. The AAI is made up of two cooling units: an underlying white unit and an overlying weakly consolidated pink unit. Radiometric data provide the same age for the two units. As both units record exactly the same well-defined paleomagnetic direction (16 sites in the white unit of AAI: Dec=173.7; Inc=31.2; alpha 95=0.7; k=2749; and 10 sites in the pink unit of AAI; Dec=173.6; Inc=30.3; alpha 95=1.2; k=1634), showing no evidence of secular variation, the time gap between emplacement of the two units is unlikely to exceed a few years. The > 50 m thick well-consolidated white underlying unit of the Arequipa airport ignimbrite provides a very specific magnetic zonation with low magnetic susceptibilities, high coercivities and unblocking temperatures of NRM above 580 degrees C indicating a Ti-poor titanohematite signature. The Anisotropy of Magnetic Susceptibility (AMS) is strongly enhanced in this layer with anisotropy values up to 1.25. The fabric delineated by AMS was not recognized neither in the field nor in thin sections, because most of the AAI consists in a massive and isotrope deposit with no visible textural fabric. Pumices deformation due to welding is only observed at the base of the thickest sections. AMS within the AAI ignimbrite show a very well defined pattern of apparent imbrications correlated to the paleotopography, with planes of foliation and lineation dipping often at more than 20 degrees toward the expected vent, buried beneath the Nevado Chachani volcanic complex. In contrast with the relatively small extent of the thick AAI, the La Joya ignimbrite covers large areas from the Altipano down the Piedmont. Ti-poor titanomagnetites are the dominant magnetic carriers and AMS values are generally lower than 1.05. Magnetic foliations are sub horizontal and lineations directions are scattered in the LJI. The AMS fabrics are probably controlled by post-depositional compaction and welding of the deposit rather than transport dynamics