PMC:3475480 / 1367-4462 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/3475480","sourcedb":"PMC","sourceid":"3475480","source_url":"https://www.ncbi.nlm.nih.gov/pmc/3475480","text":"Introduction\nCASZ1 gene is a zinc finger transcription factor that controls cell fate, although little is known about its function [1]. CASZ1 is also known as a survival-related gene that has 2 isoforms. It encodes a putative protein of 172 amino acids that localizes predominantly in the perinuclear region, as predicted for transcription factors. CASZ1 is highly expressed in many human cancer cell lines, although its expression is low in most tissues, implicating it in tumor growth [2].\nThese findings indicate that CASZ1 is important for cell proliferation, development, and differentiation, as well as carcinogenesis. However, CASZ1 has recently been reported to be significantly associated with blood pressure and hypertension in genomewide association studies (GWASs) [3]. Blood pressure GWASs by the Global Blood Pressure Genetics (Global BPgen) [4] and the Cohorts for Heart and Aging Research in Genome Epidemiology (CHARGE) consortium [5] have identified 14 independent loci that govern blood pressure or hypertension at a genomewide significance level, 7 of which were replicated in the Japanese population (CASZ1, MTHFR, ITGA9, FGF5, CYP17A1-CNNM2, ATP2B1, and CSK-ULK3) [6].\nSingle nucleotide polymorphism (SNP) rs880315, which lies in an intron of CASZ1, was one of the 7 replicate loci (p = 2.2 × 10-8, p = 4.9 × 10-12, and p = 3.0 × 10-7 for systolic blood pressure, diastolic blood pressure, and hypertension, respectively). CASZ1 was also linked to blood pressure in the Women's Genome Health Study (rs880315; p = 5.2 × 10-9 for systolic blood pressure) [7]. Recently, the CASZ1 locus was identified in 19,608 subjects of east Asian ancestry by the Asian Genetic Epidemiology Network Blood Pressure (AGEN-BP) consortium [8].\nAlthough these blood pressure GWASs have suggested that these loci control blood pressure, their function in blood pressure has not been examined. Traditionally, knockout or transgenic mice have been used to reveal gene function and can be good approaches for examining candidate genes that lie near the GWAS loci [9]. However, this process is expensive and time-consuming [10], requiring technical advances to determine their function in vivo.\nSmall interfering RNA (siRNA) is an alternative approach that has the potential to become the preferred tool for that purpose [11]. In vivo injection of siRNA reduces gene expression by 70% to 80% in certain tissues in mice, demonstrating its efficacy [12].\nHowever, specific tissues can not be targeted by in vivo injection of siRNA, and the injected siRNA is unstable in blood serum, limiting their use in delivering siRNA in vivo. It also has certain disadvantages, such as effecting inflammatory responses and toxicity [13]. Thus, developing siRNA delivery methods in animal models is a challenging but worthy effort to accelerate the discovery of novel genes [11].\nWe sought to determine whether murine Casz1 controls blood pressure by administering Casz1 siRNA to mice. A polyethylenimine-mixed siRNA complex was injected into tail veins, and changes in Casz1 mRNA and blood pressure were measured.","divisions":[{"label":"Title","span":{"begin":0,"end":12}}],"tracks":[{"project":"2_test","denotations":[{"id":"23105927-16631614-44845673","span":{"begin":132,"end":133},"obj":"16631614"},{"id":"23105927-16322216-44845674","span":{"begin":488,"end":489},"obj":"16322216"},{"id":"23105927-19430479-44845675","span":{"begin":778,"end":779},"obj":"19430479"},{"id":"23105927-19430483-44845676","span":{"begin":857,"end":858},"obj":"19430483"},{"id":"23105927-20031568-44845677","span":{"begin":949,"end":950},"obj":"20031568"},{"id":"23105927-20479155-44845678","span":{"begin":1187,"end":1188},"obj":"20479155"},{"id":"23105927-21045733-44845679","span":{"begin":1576,"end":1577},"obj":"21045733"},{"id":"23105927-21572416-44845680","span":{"begin":1742,"end":1743},"obj":"21572416"},{"id":"23105927-16684850-44845681","span":{"begin":2061,"end":2062},"obj":"16684850"},{"id":"23105927-12590264-44845682","span":{"begin":2120,"end":2122},"obj":"12590264"},{"id":"23105927-16478693-44845683","span":{"begin":2318,"end":2320},"obj":"16478693"},{"id":"23105927-20686566-44845684","span":{"begin":2444,"end":2446},"obj":"20686566"},{"id":"23105927-21078116-44845685","span":{"begin":2715,"end":2717},"obj":"21078116"},{"id":"23105927-16478693-44845686","span":{"begin":2856,"end":2858},"obj":"16478693"}],"attributes":[{"subj":"23105927-16631614-44845673","pred":"source","obj":"2_test"},{"subj":"23105927-16322216-44845674","pred":"source","obj":"2_test"},{"subj":"23105927-19430479-44845675","pred":"source","obj":"2_test"},{"subj":"23105927-19430483-44845676","pred":"source","obj":"2_test"},{"subj":"23105927-20031568-44845677","pred":"source","obj":"2_test"},{"subj":"23105927-20479155-44845678","pred":"source","obj":"2_test"},{"subj":"23105927-21045733-44845679","pred":"source","obj":"2_test"},{"subj":"23105927-21572416-44845680","pred":"source","obj":"2_test"},{"subj":"23105927-16684850-44845681","pred":"source","obj":"2_test"},{"subj":"23105927-12590264-44845682","pred":"source","obj":"2_test"},{"subj":"23105927-16478693-44845683","pred":"source","obj":"2_test"},{"subj":"23105927-20686566-44845684","pred":"source","obj":"2_test"},{"subj":"23105927-21078116-44845685","pred":"source","obj":"2_test"},{"subj":"23105927-16478693-44845686","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2_test","color":"#eccf93","default":true}]}]}}