Journal article
Transcriptome-wide landscape of pre-mRNA alternative splicing associated with metastatic colonization
Molecular cancer research, Vol.13(2), pp.305-318
02/2015
DOI: 10.1158/1541-7786.MCR-14-0366
PMCID: PMC4336826
PMID: 25274489
Abstract
Metastatic colonization is an ominous feature of cancer progression. Recent studies have established the importance of pre-mRNA alternative splicing (AS) in cancer biology. However, little is known about the transcriptome-wide landscape of AS associated with metastatic colonization. Both in vitro and in vivo models of metastatic colonization were utilized to study AS regulation associated with cancer metastasis. Transcriptome profiling of prostate cancer cells and derivatives crossing in vitro or in vivo barriers of metastasis revealed splicing factors with significant gene expression changes associated with metastatic colonization. These include splicing factors known to be differentially regulated in epithelial-mesenchymal transition (ESRP1, ESRP2, and RBFOX2), a cellular process critical for cancer metastasis, as well as novel findings (NOVA1 and MBNL3). Finally, RNA-seq indicated a large network of AS events regulated by multiple splicing factors with altered gene expression or protein activity. These AS events are enriched for pathways important for cell motility and signaling, and affect key regulators of the invasive phenotype such as CD44 and GRHL1.
Transcriptome-wide remodeling of AS is an integral regulatory process underlying metastatic colonization, and AS events affect the metastatic behavior of cancer cells.
Details
- Title: Subtitle
- Transcriptome-wide landscape of pre-mRNA alternative splicing associated with metastatic colonization
- Creators
- Zhi-xiang Lu - Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CaliforniaQin Huang - Department of Molecular Physiology and Biophysics, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, Iowa. Department of Pathology, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IowaJuw Won Park - Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CaliforniaShihao Shen - Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CaliforniaLan Lin - Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CaliforniaCollin J Tokheim - Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CaliforniaMichael D Henry - Department of Molecular Physiology and Biophysics, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, Iowa. Department of Pathology, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, Iowa. yxing@ucla.edu Michael-henry@uiowa.eduYi Xing - Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, California. yxing@ucla.edu Michael-henry@uiowa.edu
- Resource Type
- Journal article
- Publication Details
- Molecular cancer research, Vol.13(2), pp.305-318
- DOI
- 10.1158/1541-7786.MCR-14-0366
- PMID
- 25274489
- PMCID
- PMC4336826
- NLM abbreviation
- Mol Cancer Res
- ISSN
- 1541-7786
- eISSN
- 1557-3125
- Publisher
- United States
- Grant note
- P50 CA097186 / NCI NIH HHS R01 GM105431 / NIGMS NIH HHS GM105431 / NIGMS NIH HHS CA130916 / NCI NIH HHS R01 CA130916 / NCI NIH HHS
- Language
- English
- Date published
- 02/2015
- Academic Unit
- Molecular Physiology and Biophysics; Pathology; Radiation Oncology; Urology
- Record Identifier
- 9984025566202771
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