Knockdown of CSE1L Gene in Colorectal Cancer Reduces Tumorigenesis in Vitro.

Abstract

Human cellular apoptosis susceptibility (chromosomal segregation 1-like, CSE1L) gene plays a role in nuclear-to-cytoplasm transport and chromosome segregation during mitosis, cellular proliferation, and apoptosis. CSE1L is involved in colon carcinogenesis. CSE1L gene expression was assessed with three data sets using Affymetrix U133 + gene chips on normal human colonic mucosa (NR), adenomas (ADs), and colorectal carcinoma (CRC). CSE1L protein expression in CRC, AD, and NR from the same patients was measured by immunohistochemistry using a tissue microarray. We evaluated CSE1L expression in CRC cells (HCT116, SW480, and HT29) and its biological functions. CSE1L mRNA was significantly increased in all AD and CRC compared with NR (P < 0.001 and P = 0.02, respectivly). We observed a change in CSE1L staining intensity and cellular localization by immunohistochemistry. CSE1L was significantly increased during the transition from AD to CRC when compared with NR in a CRC tissue microarray (P = 0.01 and P < 0.001). HCT116, SW480, and HT29 cells also expressed CSE1L protein. CSE1L knockdown by shRNA inhibited protein, resulting in decreased cell proliferation, reduced colony formation in soft agar, and induction of apoptosis. CSE1L protein is expressed early and across all stages of CRC development. shRNA knockdown of CSE1L was associated with inhibition of tumorigenesis in CRC cells. CSE1L may represent a potential target for treatment of CRC.

• Authors: Jose M Pimiento, Kevin G Neill, Evita Henderson-Jackson, Steven A Eschrich, Dung-Tsa Chen, Kazim Husain, David Shibata, Domenico Coppola, Mokenge P Malafa
• Journal: The American journal of pathology (Am J Pathol) Vol. 186 Issue 10 Pg. 2761-8 (10 2016) ISSN: 1525-2191 [Electronic] United States
• PMID: 27521996 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Chemical References

• Cellular Apoptosis Susceptibility Protein

Topics

• Adenoma (genetics, metabolism, pathology)
• Adult
• Aged
• Aged, 80 and over
• Apoptosis (genetics)
• Carcinogenesis (genetics)
• Cell Line, Tumor
• Cell Nucleus (metabolism)
• Cell Proliferation
• Cellular Apoptosis Susceptibility Protein (genetics, metabolism)
• Colorectal Neoplasms (genetics, metabolism, pathology)
• Cytoplasm (metabolism)
• Epithelial Cells (metabolism, pathology)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Male
• Middle Aged
• Protein Transport
• Tissue Array Analysis
• Young Adult