@article{c9b73537720c4f2c8706a5aa75f9157a,
title = "Alternative microexon splicing by RBFOX2 and PTBP1 is associated with metastasis in colorectal cancer",
abstract = "The splicing of microexons (very small exons) is frequently dysregulated in the brain of individuals with autism spectrum disorder. However, little is known of the patterns, regulatory mechanisms and roles of microexon splicing in cancer. We here examined the transcriptome-wide profile of microexon splicing in matched colorectal cancer (CRC) and normal tissue specimens. Out of 1492 microexons comprising 3 to 15 nucleotides, 21 (1%) manifested differential splicing between CRC and normal tissue. The 21 genes harboring the differentially spliced microexons were enriched in gene ontology terms related to cell adhesion and migration. RNA interference-mediated knockdown experiments identified two splicing factors, RBFOX2 and PTBP1, as regulators of microexon splicing in CRC cells. RBFOX2 and PTBP1 were found to directly bind to microexon-containing pre-mRNAs and to control their splicing in such cells. Differential microexon splicing was shown to be due, at least in part, to altered expression of RBFOX2 and PTBP1 in CRC tissue compared to matched normal tissue. Finally, we found that changes in the pattern of microexon splicing were associated with CRC metastasis. Our data thus suggest that altered expression of RBFOX2 and PTBP1 might influence CRC metastasis through the regulation of microexon splicing.",
keywords = "PTBP1, RBFOX2, colorectal cancer, microexon, splicing",
author = "Yasushi Mochizuki and Ryo Funayama and Matsuyuki Shirota and Yuna Kikukawa and Masahiro Ohira and Hideaki Karasawa and Minoru Kobayashi and Shinobu Ohnuma and Michiaki Unno and Keiko Nakayama",
note = "Funding Information: We thank H. Miyoshi for providing the CSIIneo lentiviral vector; Y. Nagasawa, K. Kuroda, M. Tsuda, M. Kikuchi and M. Nakagawa for technical assistance; T. Konishi for help with preparation of the article; other laboratory members for discussion; and the Biomedical Research Core of Tohoku University Graduate School of Medicine for technical support. Our study was supported by Japan Society for the Promotion of Science (JSPS) KAKENHI grants JP20K07560 (to Ryo Funayama), JP19H04891 (to Matsuyuki Shirota), JP18K08669 (to Hideaki Karasawa), and JP17H04035, JP18H05215 and JP21H02458 (to Keiko Nakayama). Funding Information: We thank H. Miyoshi for providing the CSIIneo lentiviral vector; Y. Nagasawa, K. Kuroda, M. Tsuda, M. Kikuchi and M. Nakagawa for technical assistance; T. Konishi for help with preparation of the article; other laboratory members for discussion; and the Biomedical Research Core of Tohoku University Graduate School of Medicine for technical support. Our study was supported by Japan Society for the Promotion of Science (JSPS) KAKENHI grants JP20K07560 (to Ryo Funayama), JP19H04891 (to Matsuyuki Shirota), JP18K08669 (to Hideaki Karasawa), and JP17H04035, JP18H05215 and JP21H02458 (to Keiko Nakayama). Publisher Copyright: {\textcopyright} 2021 UICC.",
year = "2021",
month = nov,
day = "15",
doi = "10.1002/ijc.33758",
language = "English",
volume = "149",
pages = "1787--1800",
journal = "International journal of cancer. Journal international du cancer",
issn = "0020-7136",
publisher = "Wiley-Liss Inc.",
number = "10",
}