Gastric cancer (GC) is one of the most common and lethal gastrointestinal malignancies worldwide. Many studies have shown that development of GC and other malignancies is mainly driven by alterations of cellular signaling pathways. MicroRNAs (miRNAs) are small noncoding molecules that function as tumor-suppressors or oncogenes, playing an essential role in a variety of fundamental biological processes. In order to understand the functional relevance of miRNA dysregulation, studies analyzing their target genes are of major importance. Here, we chose to analyze two miRNAs, miR-20b and miR-451a, shown to be deregulated in many different malignancies, including GC. Deregulated expression of miR-20b and miR-451a was determined in GC cell lines and the INS-GAS mouse model. Using Western Blot and luciferase reporter assay we determined that miR-20b directly regulates expression of PTEN and TXNIP, and miR-451a: CAV1 and TSC1. Loss-of-function experiments revealed that down-regulation of miR-20b and up-regulation of miR-451a expression exhibits an anti-tumor effect in vitro (miR-20b: reduced viability, colony formation, increased apoptosis rate, and miR-451a: reduced colony forming ability). To summarize, the present study identified that expression of miR-20b and miR-451a are deregulated in vitro and in vivo and have a tumor suppressive role in GC through regulation of the PI3K/AKT/mTOR signaling pathway.
During the 1950s-1960s, the Merkys river basin, the largest protected area of Lithuania, underwent severe anthropogenic regulations. Within the Baltic States, the genetic diversity of Phalaris arundinacea populations is unknown and how they might be affected by anthropogenic activities such as river regulation. The objectives of this study were to compare molecular parameters (SSRs or microsatellite loci) within and among populations from natural river fragments with populations from regulated river parts. Study populations have greater genetic diversity within, rather than among, populations. The upstream portion of the Merkys basin populations had lower genetic diversity compared with further downstream. The mean number of polymorphic SSR loci was lower for populations from regulated parts of the river basin compared with natural ones. Main principle coordinate analysis revealed populations of regulated rivers at marginal positions. Bayesian clustering showed that current populations are admixtures of 3 distinct genetic groups, based on STRUCTURE analysis (K = 3 groupings) in geographic subdivisions of (a) downstream populations (Varėnė, Verseka, Upper Grūda, Lower Grūda, Upper Merkys, Lower Merkys), (b) upstream populations (Upper Šalčia, Beržė, Lower Šalčia, Visinčia, Lower Šaltykščia, Nedilė), and (c) the 2 regulated sites in the distinct geographic area of Taurupis and Upper Šaltykščia.P. arundinacea in the Merkys river basin does not all belong to a single, random-mating population encompassing its tributaries or among populations across its geographic scales. In several instances, river regulation might impair the genetic diversity of P. arundinacea populations.
The present study is aimed at evaluation of genetic diversity of populations of three Impatiens species from two countries by employing multilocus markers of two different types. The total number of individuals was 355, the number of populations for each species -native Impatiens noli-tangere and invasive -I. parviflora, I. glandulifera, was 8 (4 from Lithuania and 4 from the Czech Republic). Impatiens species were evaluated according to 8 randomly amplified polymorphic DNA (RAPD) loci and 5 inter-simple sequence repeat (ISSR) loci. Independently of the site, at the species level polymorphism was the highest for I. glandulifera at RAPD loci (35.2%, as a mean per population) and for I. noli-tangere at ISSR loci (48%). RAPD and ISSR based dendrograms for individuals and populations also principal coordinate analyses clearly clustered populations of each species according to their countries, except for ISSR based dendrogram for the populations of I. noli-tangere. Estimated at ISSR loci, molecular variance among the populations of the two countries was much smaller for native I. noli-tangere (7.3%), when compared to invasive I. parviflora (49.7%) or I. glandulifera (45.6%). Genetic differentiation among the populations was the smallest for I. noli-tangere (G ST = 0.36). The populations of both invasive species from the Czech Republic were more polymorphic at ISSR loci, when compared to those from Lithuania. Mantel test showed significant correlations between geographic and genetic distances in the case of both DNA markers. The Czech Republic's populations were bigger in size, grew in higher altitudes, mean annual temperatures of the site were higher by several degrees and mean annual rainfall was lower compared to Lithuania's. Polymorphisms at RAPD and ISSR loci might play different role for viability of populations of Impatiens species. ISSR markers were more useful for the assessment of genetic differences between native and invasive Impatiens species.
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