title: From General Aberrant Alternative Splicing in Cancers and Its Therapeutic Application to the Discovery of an Oncogenic DMTF1 Isoform.
abstract: Alternative pre-mRNA splicing is a crucial process that allows the generation of diversified RNA and protein products from a multi-exon gene. In tumor cells, this mechanism can facilitate cancer development and progression through both creating oncogenic isoforms and reducing the expression of normal or controllable protein species. We recently demonstrated that an alternative cyclin D-binding myb-like transcription factor 1 (DMTF1) pre-mRNA splicing isoform, DMTF1β, is increasingly expressed in breast cancer and promotes mammary tumorigenesis in a transgenic mouse model. Aberrant pre-mRNA splicing is a typical event occurring for many cancer-related functional proteins. In this review, we introduce general aberrant pre-mRNA splicing in cancers and discuss its therapeutic application using our recent discovery of the oncogenic DMTF1 isoform as an example. We also summarize new insights in designing novel targeting strategies of cancer therapies based on the understanding of deregulated pre-mRNA splicing mechanisms.
authors.affiliation: College of Life Science, Northeast Forestry University, Harbin 150040, China. tianna@nefu.edu.cn.
authors.forename: Na
authors.initials: N
authors.lastname: Tian
authors.affiliation: College of Life Science, Northeast Forestry University, Harbin 150040, China. lijialiang@nefu.edu.cn.
authors.forename: Jialiang
authors.initials: J
authors.lastname: Li
authors.affiliation: College of Life Science, Northeast Forestry University, Harbin 150040, China. jmshi@nefu.edu.cn.
authors.forename: Jinming
authors.initials: J
authors.lastname: Shi
authors.affiliation: College of Life Science, Northeast Forestry University, Harbin 150040, China. gcsui@nefu.edu.cn.|Department of Cancer Biology and Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA. gcsui@nefu.edu.cn.
authors.forename: Guangchao
authors.initials: G
authors.lastname: Sui
mesh_terms: D017398:Alternative Splicing / Q000187:drug effects; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology* / Q000628:therapy*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy; D020033:Protein Isoforms / Q000187:drug effects / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; C491126:DMTF1 protein, human; D020033:Protein Isoforms; D014157:Transcription Factors
keywords: DMTF1; alternative splicing; cancer therapy; tumorigenesis