Altered expression of long non-coding RNA GAS5 in digestive tumors

Cancer has become one of the most important diseases that affect human health and life. The effects of cancer in the digestive system are particularly prominent. Recently, long non-coding RNA (lncRNA) has attracted the attention of more and more researchers and has become an emerging field of gene research. The lncRNA growth arrest-specific 5 (GAS5) is a novel lncRNA that has attracted the attention of researchers in recent years and plays an important role in the development of tumors, especially in digestive system tumors. GAS5 was first identified in a mouse cDNA library. It was generally considered that it has the role of tumor suppressor genes, but there are still studies that have a certain ability to promote cancer. Furthermore, the 5-bp indel polymorphism (rs145204276) in the GAS5 promoter region also has a carcinogenic effect. The discovery of GAS5 and in-depth study of single nucleotide polymorphism (SNP) mechanism can provide a new way for the prevention and treatment of digestive system tumors.

Abstract P193: Platelet-derived Growth Factor B: a Novel Determinant of Juxtaglomerular Cell Phenotypic Plasticity?

Renin, a key component in the regulation of blood pressure in mammals, is produced by the rare and highly specialized juxtaglomerular (JG) cells of the kidney. JG cells may be derived from vascular smooth muscle cells (VSMC) and they can reversibly differentiate in response to changes in salt, blood pressure and treatment with anti-hypertensive medications. The biochemical mechanism responsible for this phenotypic plasticity is currently unknown. Ligands involved in VSMC differentiation include platelet-derived growth factor B (PDGF-B), secreted acidic protein rich in cysteine (SPARC), type-C natriuretic peptide (NPPC), follistatin related protein (FSTL1) and lactose-binding lectin 1 (LGALS1). To test for the role of these factors in JG cell plasticity we used (pro)renin-producing As4.1 cells derived from a mouse JG cell targeted tumor. As4.1 cells were incubated for 48 hours with conditioned medium derived from human embryonic kidney (HEK) 293 cells transfected with the mouse cDNA encoding these ligands, after which both medium and cell lysate were collected. Renin and prorenin were measured using the angiotensin I generation assay. Under control conditions, the medium contained predominantly (>95%) prorenin. In contrast, the cell lysate contained renin only, at levels corresponding to <1% of the total amount of renin+prorenin in the medium (i.e., 161±61 μg angiotensin I/ml.hr, mean±SEM). Among the tested ligands, only PDGF-B affected the medium prorenin and cellular renin levels, decreasing both in parallel by 68±5% and 53±10%, respectively. In addition, PDGF-B-exposed cells changed their morphology to display a more elongated, densely packed and aligned shape with no apparent alteration in their viability. In conclusion, our data suggest that PDGF-B might be one of the factors involved in JG cell phenotypic plasticity.

Species-specific Differences among KCNMB3 BK β3 Auxiliary Subunits: Some β3 N-terminal Variants May Be Primate-specific Subunits

The KCNMB3 gene encodes one of a family of four auxiliary β subunits found in the mammalian genome that associate with Slo1 α subunits and regulate BK channel function. In humans, the KCNMB3 gene contains four N-terminal alternative exons that produce four functionally distinct β3 subunits, β3a–d. Three variants, β3a–c, exhibit kinetically distinct inactivation behaviors. Since investigation of the physiological roles of BK auxiliary subunits will depend on studies in rodents, here we have determined the identity and functional properties of mouse β3 variants. Whereas β1, β2, and β4 subunits exhibit 83.2%, 95.3%, and 93.8% identity between mouse and human, the mouse β3 subunit, excluding N-terminal splice variants, shares only 62.8% amino acid identity with its human counterpart. Based on an examination of the mouse genome and screening of mouse cDNA libraries, here we have identified only two N-terminal candidates, β3a and β3b, of the four found in humans. Both human and mouse β3a subunits produce a characteristic use-dependent inactivation. Surprisingly, whereas the hβ3b exhibits rapid inactivation, the putative mβ3b does not inactivate. Furthermore, unlike hβ3, the mβ3 subunit, irrespective of the N terminus, mediates a shift in gating to more negative potentials at a given Ca2+ concentration. The shift in gating gradually is lost following patch excision, suggesting that the gating shift involves some regulatory process dependent on the cytosolic milieu. Examination of additional genomes to assess conservation among splice variants suggests that the putative mβ3b N terminus may not be a true orthologue of the hβ3b N terminus and that both β3c and β3d appear likely to be primate-specific N-terminal variants. These results have three key implications: first, functional properties of homologous β3 subunits may differ among mammalian species; second, the specific physiological roles of homologous β3 subunits may differ among mammalian species; and, third, some β3 variants may be primate-specific ion channel subunits.

Differential expression profiling of the blind subterranean mole rat Spalax ehrenbergi superspecies: bioprospecting for hypoxia tolerance

The blind subterranean mole rat of the Spalax ehrenbergi superspecies, living underground and exposed to fluctuating oxygen and carbon dioxide levels, is an excellent model of hypoxic tolerance. Unique structural and functional adaptations of the cardiovascular and respiratory systems allow these underground mammals to survive at severely reduced oxygen tension. Elucidation of the natural variation and evolutionary changes under hypoxia within this superspecies may have biomedical applications in ischemic syndromes and cancer. In this study, we have compared expression profiles of muscle tissue at normoxic (21%) and hypoxic (3%) levels of oxygen concentration between two allospecies of the S. ehrenbergi superspecies exhibiting differential hypoxia tolerance in accordance with their ecological regimes. Profiling was performed by cross-species hybridization using a mouse cDNA array containing 15,000 gene elements. Results uncover species-specific responses to hypoxic stress among numerous genes involved in angiogenesis, apoptosis, and oxidative stress management. Among the most striking results are differential expressions of cardiac ankyrin repeat protein ( Carp), activating transcription factor 3 ( Atf3), LIM and cysteine-rich domains 1 ( Lmcd1), cysteine and glycine-rich protein 2 ( Csrp2), and ras homolog gene family, member B ( RhoB). These findings support the hypothesis that allospecies of the S. ehrenbergi superspecies are variably adapted to fluctuating oxygen tension. Differences may involve specific metabolic pathways and functional adaptations at the structural and molecular levels.