Mitotic checkpoint regulator RAE1 promotes tumor growth in colorectal cancer.

Abstract

Microtubules are among the most successful targets for anticancer therapy because they play important roles in cell proliferation as they constitute the mitotic spindle, which is critical for chromosome segregation during mitosis. Hence, identifying new therapeutic targets encoding proteins that regulate microtubule assembly and function specifically in cancer cells is critical. In the present study, we identified a candidate gene that promotes tumor progression, ribonucleic acid export 1 (RAE1), a mitotic checkpoint regulator, on chromosome 20q through a bioinformatics approach using datasets of colorectal cancer (CRC), including The Cancer Genome Atlas (TCGA). RAE1 was ubiquitously amplified and overexpressed in tumor cells. High expression of RAE1 in tumor tissues was positively associated with distant metastasis and was an independent poor prognostic factor in CRC. In vitro and in vivo analysis showed that RAE1 promoted tumor growth, inhibited apoptosis, and promoted cell cycle progression, possibly with a decreased proportion of multipolar spindle cells in CRC. Furthermore, RAE1 induced chemoresistance through its anti-apoptotic effect. In addition, overexpression of RAE1 and significant effects on survival were observed in various types of cancer, including CRC. In conclusion, we identified RAE1 as a novel gene that facilitates tumor growth in part by inhibiting apoptosis and promoting cell cycle progression through stabilizing spindle bipolarity and facilitating tumor growth. We suggest that it is a potential therapeutic target to overcome therapeutic resistance of CRC.

• Authors: Yuta Kobayashi, Takaaki Masuda, Atsushi Fujii, Dai Shimizu, Kuniaki Sato, Akihiro Kitagawa, Taro Tobo, Yuki Ozato, Hideyuki Saito, Shotaro Kuramitsu, Miwa Noda, Hajime Otsu, Tsunekazu Mizushima, Yuichiro Doki, Hidetoshi Eguchi, Masaki Mori, Koshi Mimori
• Journal: Cancer science (Cancer Sci) Vol. 112 Issue 8 Pg. 3173-3189 (Aug 2021) ISSN: 1349-7006 [Electronic] England
• PMID: 34008277 (Publication Type: Journal Article)
• Copyright: © 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Chemical References

• Nuclear Matrix-Associated Proteins
• Nucleocytoplasmic Transport Proteins
• RAE1 protein, human
• Paclitaxel

Topics

• Aged
• Animals
• Caco-2 Cells
• Cell Cycle
• Cell Line, Tumor
• Colorectal Neoplasms (drug therapy, genetics, metabolism, pathology)
• Databases, Genetic
• Drug Resistance, Neoplasm
• Female
• Gene Amplification
• Gene Expression Regulation, Neoplastic
• Humans
• Male
• Mice
• Middle Aged
• Nuclear Matrix-Associated Proteins (genetics)
• Nucleocytoplasmic Transport Proteins (genetics)
• Paclitaxel
• Prognosis
• Up-Regulation