title: Sleeping Beauty transposon system for genetic etiological research and gene therapy of cancers.
abstract: Carcinogenesis is etiologically associated with somatic mutations of critical genes. Recently, a number of somatic mutations and key molecules have been found to be involved in functional networks affecting cancer progression. Suitable animal models are required to validate cancer-promoting or -inhibiting capacities of these mutants and molecules. Sleeping Beauty transposon system consists of a transposon that carries gene(s) of interest and a transposase that recognizes, excises, and reinserts genes in given location of the genome. It can create both gain-of-function and loss-of-function mutations, thus being frequently chosen to investigate the etiological mechanisms and gene therapy for cancers in animal models. In this review, we summarized current advances of Sleeping Beauty transposon system in revealing molecular mechanism of cancers and improving gene therapy. Understanding molecular mechanisms by which driver mutations contribute to carcinogenesis and metastasis may pave the way for the development of innovative prophylactic and therapeutic strategies against malignant diseases.
authors.affiliation: a Department of Epidemiology ; Second Military Medical University ; Shanghai , China.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Hou
authors.forename: Yan
authors.initials: Y
authors.lastname: Du
authors.forename: Yang
authors.initials: Y
authors.lastname: Deng
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Wu
authors.forename: Guangwen
authors.initials: G
authors.lastname: Cao
mesh_terms: D000818:Animals; D004251:DNA Transposable Elements; D018014:Gene Transfer Techniques; D036281:Genetic Research; D015316:Genetic Therapy; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000628:therapy*
chemical_list: D004251:DNA Transposable Elements
keywords: 7, 12-dimethylbenzanthracene/12-O-tetradecanoylphorbol-13-acetate; Alb-Cre, Albumin promoter-Cre; CAG promoter, CMV enhancer/chicken β-actin promoter; CAR, chimeric antigen receptor; CIS, common insertion site; CMV, chimeric cytomegalovirus; CRC, colorectal cancer; Cre, cyclization recombination enzyme; DDE, Asp, Asp, Glu; DMBA/TPA; DR, direct orientation; Fah, fumarylacetoacetate hydrolase gene; GWAS, gnome wide analysis study; HBV, Hepatitis B Virus; HBx, HBV X protein; HCC, hepatocellular carcinoma; IRs, inverted repeat sequences; LsL, loxP-stop-loxP; MPNSTs, malignant peripheral nerve sheath tumor; MSCV, murine stem cell virus; PAI, Pro, Ala, Ile; PBMCs, peripheral blood mononuclear cells; RED, Arg, Glu, Asp; RosaSBaseLsL, Cre-inducible SBase allele; Rtl1, Retrotransposon-like 1; SB, Sleeping Beauty; SBase, Sleeping Beauty transposase; Sleeping Beauty transposon system; StatinAE, angiostatin-endostatin fusion gene; Trp53, transformation related protein 53; animal model; driver; gene function; gene therapy; malignant diseases; sgRNA, single guide RNA; shp53, short hairpin RNA against the Trp53 gene; somatic mutation