Long non-coding RNAs CCAT1 and CCAT2 in colorectal liver metastases are tumorsuppressive via MYC interaction and might predict patient outcomes

Sep 24, 2026

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Background: Liver metastases greatly limit long-term survival in colorectal cancer, and CCAT1/CCAT2 lncRNAs had been linked to poor prognosis in primary tumors. Methods: Expression of CCAT1, CCAT2 and MYC was assessed in 97 colorectal liver metastasis and paired normal liver samples using RT-qPCR and Multiplex ELISA, then related to clinicopathological features and survival. Functional assays used siRNA knockdown of CCAT1, CCAT2 and MYC in Colo205 and HROC277Met2. Results: Higher CCAT1/CCAT2 and MYC associated with longer progression-free survival after resection; CCAT1 also linked to improved overall survival. Knockdown increased migration and invasion and altered components of Wnt signaling. Conclusion: CCAT1 and CCAT2 act tumor-suppressively by suppressing Wnt signaling directly and indirectly via MYC, potentially limiting metastatic spread.

LanguageEnglish

CategoryResearch & Report

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Pages15

Reading Time38 min

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Abstract

Background

Methods

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PLOS ONE OPEN ACCESS Citation: Franz C, Wuehrl M, Hartmann S, Klupp F, Schmidt T, Schneider M (2023) Long non-coding RNAs CCAT1 and CCAT2 in colorectal liver metastases are tumor-suppressive via MYC interaction and might predict patient outcomes. PLoS ONE 18(6): e0286486 . [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.1371/journal.pone](10.1371/journal.pone).0286486 Editor: Klaus Roemer, Universitat des Saarlandes, GERMANY Received: January 30, 2023 Accepted: May 17, 2023 Published: June 22, 2023 Copyright: © 2023 Franz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: Data cannot be shared publicly because of privacy, ethical and federal restrictions of the Ethics Committee of the Medical Faculty of the University of Heidelberg and the German Federal Data Protection Act. Data are available for researchers who meet the criteria for research cooperation and access to confidential data from the Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, INF 420, D-69120 Heidelberg. RESEARCH ARTICLE Long non-coding RNAs CCAT1 and CCAT2 in colorectal liver metastases are tumorsuppressivevia MYC interaction and might predict patient outcomes Clemens Franz☯, Michael Wuehrl☯, Sibylle Hartmann, Fee Klupp, Thomas Schmidt, Martin Schneider * Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany ☯ These authors contributed equally to this work. * martin.schneider@med. uni-heidelberg.de Abstract Background Liver metastases severely reduce the long term survival of colorectal cancer patients. Long non-coding RNAs (lncRNAs) CCAT1 and CCAT2 have previously been found to be associated with impaired patient outcomes in primary colorectal cancer. We aimed to elucidate the role of CCAT1 and CCAT2 in colorectal liver metastases. Methods Total RNA was isolated from 97 human tissue samples of colorectal liver metastases and adjacent normal liver tissue. Gene expression analysis was performed by RT-qPCR and Multiplex ELISA and correlated with patient characteristics and survival. Gene expression, cancer cell migration, invasion, and proliferation were studied after siRNA-mediated knockdown of CCAT1, CCAT2, and MYC in metastatic colorectal cancer cell lines Colo205 and HROC277Met2 . Results Elevated expression levels of lncRNAs CCAT1 and CCAT2, and their common target MYCin colorectal liver metastases were associated with prolonged progression-free survival after liver resection. High expression of CCAT1 was likewise associated with prolonged overall survival. Knockdown of CCAT1, CCAT2, and MYC resulted in increased migratory and invasive potential in metastatic colorectal cancer cell lines. Gene expression analysis revealed alterations in constituents of Wnt signaling following knockdown. Conclusion Our findings demonstrate tumor-suppressive functions of lncRNAs CCAT1 and CCAT2 in colorectal liver metastases. They suppress Wnt signaling directly and indirectly through Funding: CF was supported for this study by the Heidelberger Stiftung Chirurgie, project “noncoding RNAs in colorectal cancer” and by the Deutsche Krebs-und Scharlachstiftung, project“Signalwege nicht kodierender RNAs beim metastasierten kolorektalen Karzinom”. We acknowledge financial support by Deutsche Forschungs-gemeinschaft (DFG) within the funding programme „Open Access Publication“ as well as by Heidelberg University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing interests: The authors have declared that no competing interests exist. target gene MYC and might prevent further metastatic spread from colorectal liver metastases.

FAQs

What was the study aiming to clarify about CCAT1 and CCAT2 in colorectal cancer?

To elucidate the role of lncRNAs CCAT1 and CCAT2 specifically in colorectal liver metastases and how they may relate to patient outcomes.

How were CCAT1, CCAT2, and MYC expression levels measured?

Total RNA from 97 tissue samples was analyzed using RT-qPCR and Multiplex ELISA, and the results were correlated with patient characteristics and survival.

What happened to cell behavior when CCAT1, CCAT2, and MYC were knocked down?

siRNA knockdown increased migratory and invasive potential in metastatic colorectal cancer cell lines and changed constituents of Wnt signaling.

Sep 24, 2026

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