Transcriptome-wide landscape of pre-mRNA alternative splicing associated with metastatic colonization.

Abstract

UNLABELLED:

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.

IMPLICATIONS:

Transcriptome-wide remodeling of AS is an integral regulatory process underlying metastatic colonization, and AS events affect the metastatic behavior of cancer cells.

• Authors: Zhi-xiang Lu, Qin Huang, Juw Won Park, Shihao Shen, Lan Lin, Collin J Tokheim, Michael D Henry, Yi Xing
• Journal: Molecular cancer research : MCR (Mol Cancer Res) Vol. 13 Issue 2 Pg. 305-18 (Feb 2015) ISSN: 1557-3125 [Electronic] United States
• PMID: 25274489 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: ©2014 American Association for Cancer Research.

Chemical References

• RNA, Messenger

Topics

• Alternative Splicing
• Animals
• Cell Line, Tumor
• Gene Expression Profiling (methods)
• Gene Expression Regulation, Neoplastic
• Humans
• Male
• Mice
• Models, Biological
• Molecular Sequence Data
• Neoplasm Metastasis
• Oligonucleotide Array Sequence Analysis (methods)
• Prostatic Neoplasms (genetics, pathology)
• RNA, Messenger (genetics)
• Sequence Analysis, RNA