Full Text | PDF

Theranostics 2017; 7(19):4836-4849. doi:10.7150/thno.20942

Research Paper

Long non-coding RNA UICLM promotes colorectal cancer liver metastasis by acting as a ceRNA for microRNA-215 to regulate ZEB2 expression

Dong-liang Chen^1*, Yun-xin Lu^1*, Jia-xing Zhang^2*, Xiao-li Wei^1*, Feng Wang¹, Zhao-lei Zeng¹, Zhi-zhong Pan¹, Yun-fei Yuan¹, Feng-hua Wang¹, Helene Pelicano³, Paul J. Chiao³, Peng Huang³, Dan Xie¹, Yu-hong Li¹, Huai-qiang Ju^1✉, Rui-hua Xu^1✉

1. State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, PR China;
2. Department of Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, PR China;
3. Department of Molecular and Cellular Oncology, the University of Texas MDAnderson Cancer Center, Houston, TX77030, USA.
* These authors contributed equally to this work

Abstract

Long non-coding RNAs (lncRNAs) are involved in the pathology of various tumors, including colorectal cancer (CRC). However, the role of lncRNA in CRC liver metastasis remains unclear. Methods: a microarray was performed to identify the differentially expressed lncRNAs between CRC tissues with and without liver metastasis. Survival analysis was evaluated using the Kaplan-Meier method and assessed using the log-rank test. In vitro and in vivo assays were preformed to explore the biological effects of the differentially expressed lncRNA in CRC cells. Results: the lncRNA UICLM (up-regulated in colorectal cancer liver metastasis) was significantly up-regulated in cases of CRC with liver metastasis. Moreover, UICLM expression was higher in CRC tissues than in normal tissues, and UICLM expression was associated with poor patient survival. Knockdown of UICLM inhibited CRC cell proliferation, invasion, epithelial-mesenchymal transition (EMT) and CRC stem cell formation in vitro as well as tumor growth and liver metastasis in vivo. Ectopic expression of UICLM promoted CRC cell proliferation and invasion. Mechanistic investigations revealed that UICLM induced its biological effects by regulating ZEB2, as the oncogenesis facilitated by UICLM was inhibited by ZEB2 depletion. Further study indicated that UICLM acted as a competing endogenous RNA (ceRNA) for miR-215 to regulate ZEB2 expression. Conclusions: taken together, our findings demonstrate how UICLM induces CRC liver metastasis and may offer a novel prognostic marker and therapeutic target for this disease.

Keywords: long non-coding RNA, CRC, lncRNA UICLM, liver metastasis.