Long Non-coding RNA UICLM Promotes Colorectal Cancer Liver Metastasis by Acting As a CeRNA for MicroRNA-215 to Regulate ZEB2 Expression

Overview

Journal Theranostics

Date 2017 Dec 1

PMID 29187907

Citations 154

Authors

Dong-Liang Chen

Yun-Xin Lu

Jia-Xing Zhang

Xiao-Li Wei

Feng Wang

Zhao-Lei Zeng

Zhi-Zhong Pan

Yun-Fei Yuan

Feng-Hua Wang

Helene Pelicano

Paul J Chiao

Peng Huang

Dan Xie

Yu-Hong Li

Huai-Qiang Ju

Rui-Hua Xu

Affiliations

Soon will be listed here.

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. 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. and assays were preformed to explore the biological effects of the differentially expressed lncRNA in CRC cells. 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 as well as tumor growth and liver metastasis . 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. taken together, our findings demonstrate how UICLM induces CRC liver metastasis and may offer a novel prognostic marker and therapeutic target for this disease.

Citing Articles

Deciphering the mechanisms of long non-coding RNAs in ferroptosis: insights into its clinical significance in cancer progression and immunology.

Ou S, Nie X, Qiu X, Jin X, Wu G, Zhang R Cell Death Discov. 2025; 11(1):14.

PMID: 39827195 PMC: 11743196. DOI: 10.1038/s41420-025-02290-6.

New sights on long non-coding RNAs in glioblastoma: A review of molecular mechanism.

Bagheri-Mohammadi S, Karamivandishi A, Mahdavi S, Siahposht-Khachaki A Heliyon. 2024; 10(21):e39744.

PMID: 39553554 PMC: 11564028. DOI: 10.1016/j.heliyon.2024.e39744.

RRFERV stabilizes TEAD1 expression to mediate nasopharyngeal cancer radiation resistance rendering tumor cells vulnerable to ferroptosis.

Xu Q, Wen X, Huang C, Lin Z, Xu Z, Sun C Int J Surg. 2024; 111(1):450-466.

PMID: 39352125 PMC: 11745583. DOI: 10.1097/JS9.0000000000002099.

Circular RNA circNCOA3 promotes tumor progression and anti-PD-1 resistance in colorectal cancer.

Chen D, Chen N, Sheng H, Zhang D Cancer Drug Resist. 2024; 7:9.

PMID: 38510750 PMC: 10951830. DOI: 10.20517/cdr.2023.151.

Long non-coding RNA LINC01554 overexpression suppresses viability, migration, and invasion of liver cancer cells through regulating miR-148b-3p/EIF4E3.

Ren X, Wang X, Song H, Zhang C, Yuan J, He J Heliyon. 2024; 10(6):e27319.

PMID: 38501022 PMC: 10945188. DOI: 10.1016/j.heliyon.2024.e27319.

References

Ulitsky I, Bartel D . lincRNAs: genomics, evolution, and mechanisms. Cell. 2013; 154(1):26-46. PMC: 3924787. DOI: 10.1016/j.cell.2013.06.020. View

Wang K, Chang H . Molecular mechanisms of long noncoding RNAs. Mol Cell. 2011; 43(6):904-14. PMC: 3199020. DOI: 10.1016/j.molcel.2011.08.018. View

Wang K, Yang Y, Liu B, Sanyal A, Corces-Zimmerman R, Chen Y . A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression. Nature. 2011; 472(7341):120-4. PMC: 3670758. DOI: 10.1038/nature09819. View

Kraljevic Pavelic S, Sedic M, Bosnjak H, Spaventi S, Pavelic K . Metastasis: new perspectives on an old problem. Mol Cancer. 2011; 10:22. PMC: 3052211. DOI: 10.1186/1476-4598-10-22. View

Ye M, Zhang J, Miao Q, Yao L, Zhang J . Curcumin promotes apoptosis by activating the p53-miR-192-5p/215-XIAP pathway in non-small cell lung cancer. Cancer Lett. 2014; 357(1):196-205. DOI: 10.1016/j.canlet.2014.11.028. View

Thiery J, Acloque H, Huang R, Nieto M . Epithelial-mesenchymal transitions in development and disease. Cell. 2009; 139(5):871-90. DOI: 10.1016/j.cell.2009.11.007. View

Lee J, Park M, Park J, Lee H, Shin D, Kang Y . Loss of the polycomb protein Mel-18 enhances the epithelial-mesenchymal transition by ZEB1 and ZEB2 expression through the downregulation of miR-205 in breast cancer. Oncogene. 2013; 33(10):1325-35. DOI: 10.1038/onc.2013.53. View

Tsai M, Manor O, Wan Y, Mosammaparast N, Wang J, Lan F . Long noncoding RNA as modular scaffold of histone modification complexes. Science. 2010; 329(5992):689-93. PMC: 2967777. DOI: 10.1126/science.1192002. View

Ling H, Spizzo R, Atlasi Y, Nicoloso M, Shimizu M, Redis R . CCAT2, a novel noncoding RNA mapping to 8q24, underlies metastatic progression and chromosomal instability in colon cancer. Genome Res. 2013; 23(9):1446-61. PMC: 3759721. DOI: 10.1101/gr.152942.112. View

10.

Li X, Roslan S, Johnstone C, Wright J, Bracken C, Anderson M . MiR-200 can repress breast cancer metastasis through ZEB1-independent but moesin-dependent pathways. Oncogene. 2013; 33(31):4077-88. DOI: 10.1038/onc.2013.370. View

11.

Huang J, Zhou N, Watabe K, Lu Z, Wu F, Xu M . Long non-coding RNA UCA1 promotes breast tumor growth by suppression of p27 (Kip1). Cell Death Dis. 2014; 5:e1008. PMC: 4040676. DOI: 10.1038/cddis.2013.541. View

12.

Jiang C, Li X, Zhao H, Liu H . Long non-coding RNAs: potential new biomarkers for predicting tumor invasion and metastasis. Mol Cancer. 2016; 15(1):62. PMC: 5043609. DOI: 10.1186/s12943-016-0545-z. View

13.

Chang G, Rodriguez-Bigas M, Skibber J, Moyer V . Lymph node evaluation and survival after curative resection of colon cancer: systematic review. J Natl Cancer Inst. 2007; 99(6):433-41. DOI: 10.1093/jnci/djk092. View

14.

Shi Y, Wang Y, Luan W, Wang P, Tao T, Zhang J . Long non-coding RNA H19 promotes glioma cell invasion by deriving miR-675. PLoS One. 2014; 9(1):e86295. PMC: 3900504. DOI: 10.1371/journal.pone.0086295. View

15.

Esteller M . Non-coding RNAs in human disease. Nat Rev Genet. 2011; 12(12):861-74. DOI: 10.1038/nrg3074. View

16.

Hou Y, Zhen J, Xu X, Zhen K, Zhu B, Pan R . miR-215 functions as a tumor suppressor and directly targets ZEB2 in human non-small cell lung cancer. Oncol Lett. 2015; 10(4):1985-1992. PMC: 4579799. DOI: 10.3892/ol.2015.3587. View

17.

Manfredi S, Lepage C, Hatem C, Coatmeur O, Faivre J, Bouvier A . Epidemiology and management of liver metastases from colorectal cancer. Ann Surg. 2006; 244(2):254-9. PMC: 1602156. DOI: 10.1097/01.sla.0000217629.94941.cf. View

18.

Mani S, Guo W, Liao M, Eaton E, Ayyanan A, Zhou A . The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell. 2008; 133(4):704-15. PMC: 2728032. DOI: 10.1016/j.cell.2008.03.027. View

19.

Peng W, Si S, Zhang Q, Li C, Zhao F, Wang F . Long non-coding RNA MEG3 functions as a competing endogenous RNA to regulate gastric cancer progression. J Exp Clin Cancer Res. 2015; 34:79. PMC: 4529701. DOI: 10.1186/s13046-015-0197-7. View

20.

Markowitz S, Bertagnolli M . Molecular origins of cancer: Molecular basis of colorectal cancer. N Engl J Med. 2009; 361(25):2449-60. PMC: 2843693. DOI: 10.1056/NEJMra0804588. View