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

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.

Integrated analysis of long noncoding RNA associated‐competing endogenous RNA as prognostic biomarkers in clear cell renal carcinoma

“…Furthermore, lncRNA were able to compete with mRNA for the binding sites of miRNA which affect the expression of mRNA through MRE. For example, the lncRNA UICLM acted as a ceRNA for miR‐215 to regulate ZEB2 expression in colorectal cancer . In gastric cancer, the lncRNA BC0032469 upregulated hTERT expression by sponging miR‐1207, which promoted proliferation .…”

Identification of potential hub genes via bioinformatics analysis combined with experimental verification in colorectal cancer

“…At present, microarrays technology combined with bioinformatics analysis is a very efficient method to identify potential hub genes in CRC. It is possible to detect differentially expressed messenger RNAs (mRNAs), microRNAs, and long noncoding RNAs 8‐10 . By using this technique, we can find many differentially expressed genes, which play key roles in the occurrence and development of CRC.…”

LINC01303 functions as a competing endogenous RNA to regulate EZH2 expression by sponging miR‐101‐3p in gastric cancer

“…There is increasing evidence that lncRNA can be used as a biomarker for the diagnosis and prognosis of various cancers, such as colorectal cancer, breast cancer, breast cancer, liver cancer and gastric cancer . In addition, in the study of liver metastases from colorectal cancer, it was found that lncRNA UICLM inhibits the expression of miR‐150‐5p by competitive endogenous RNA, thereby promoting liver metastasis of colorectal cancer . Long non‐coding RNA can not only regulate gene expression as a competitive endogenous RNA, but also regulate epigenetics by binding to related proteins.…”