Colon adenocarcinoma is a common cause of cancer-related deaths worldwide. Epithelial-mesenchymal transition is a major regulator of cancer metastasis, and increased understanding of this process is essential to improve patient outcomes. Long non-coding RNA (lncRNA) are important regulators of carcinogenesis. To identify lncRNAs associated with colon carcinogenesis, we performed an exploratory differential gene expression analysis comparing paired colon adenocarcinoma and normal colon epithelium using an RNA-sequencing data set. This analysis identified lncRNA ZFAS1 as significantly increased in colon cancer compared to normal colon epithelium. This finding was validated in an institutional cohort using laser capture microdissection. ZFAS1 was also found to be principally located in the cellular cytoplasm. ZFAS1 knockdown was associated with decreased cellular proliferation, migration, and invasion in two colon cancer cell lines (HT29 and SW480). MicroRNA-200b and microRNA-200c (miR-200b and miR-200c) are experimentally validated targets of ZFAS1, and this interaction was confirmed using reciprocal gene knockdown. ZFAS1 knockdown regulated ZEB1 gene expression and downstream targets E-cadherin and vimentin. Knockdown of miR-200b or miR-200c reversed the effect of ZFAS1 knockdown in the ZEB1/E-cadherin, vimentin signaling cascade, and the effects of cellular migration and invasion, but not cellular proliferation. ZFAS1 knockdown was also associated with decreased tumor growth in an in vivo mouse model. These results demonstrate the critical importance of ZFAS1 as a regulator of the miR-200/ZEB1/E-cadherin, vimentin signaling cascade.

Document Type


Publication Date


Notes/Citation Information

Published in Cell Death Discovery, v. 7, issue 1, article no. 61.

© The Author(s) 2021

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.

Digital Object Identifier (DOI)


Funding Information

This work was supported by the John W. Price and Barbara Thruston Atwood Price Trust and a grant from the Mary K. Oxley Foundation. This work was supported by the University of Louisville Cancer Education Program (NIH 2R25CA134283-06A1) and the American Society for Colon & Rectal Surgeons Medical Student Research Initiation Grant.

Related Content

Research data available upon request.

41420_2021_427_MOESM1_ESM.docx (14 kB)
Supplementary Figure Legends

41420_2021_427_MOESM2_ESM.docx (12 kB)
Supplementary Table 1

41420_2021_427_MOESM3_ESM.docx (12 kB)
Supplementary Table 2

41420_2021_427_MOESM4_ESM.docx (12 kB)
Supplementary Table 3

41420_2021_427_MOESM5_ESM.docx (12 kB)
Supplementary Table 4

41420_2021_427_MOESM6_ESM.tif (1361 kB)
Supplementary Figure 1

41420_2021_427_MOESM7_ESM.tif (983 kB)
Supplementary Figure 2

41420_2021_427_MOESM8_ESM.docx (21 kB)
Supplementary methods