ZEB1-AS1 Initiates a MiRNA-mediated CeRNA Network to Facilitate Gastric Cancer Progression

Overview

Journal Cancer Cell Int

Publisher Biomed Central

Date 2019 Feb 19

PMID 30774556

Citations 15

Authors

Ming-Hui Ma

Jia-Xiang An

Cheng Zhang

Jie Liu

Yu Liang

Chun-Dong Zhang

Zhen Zhang

Dong-Qiu Dai

Affiliations

Soon will be listed here.

Abstract

Background: Currently, cancer-related competing endogenous RNA (ceRNA) networks are attracting significant interest. As long noncoding RNA ZEB1-AS1 has been reported to function as an oncogene due to sponging microRNAs (miRNAs) in several cancers, we hypothesized that it could interact with specific miRNAs to form regulatory networks and facilitate the growth of gastric cancer (GC).

Methods: MiRNAs interacting with ZEB1-AS1 were screened for and selected by bioinformatics analysis. Overexpression or repression of ZEB1-AS1 was performed to determine whether it could regulate selected miRNAs. Quantitative real-time polymerase chain reactions (qPCR) validated the expression profiles of ZEB1-AS1 and miR-149-3p in GC cell lines and tissue. Statistical analysis determined the clinical significance of ZEB1-AS1 in relation to miR-149-3p. Cell counting, wound healing and transwell assays were performed to assess cell proliferation, migration and invasion. A luciferase reporter assay was utilized to confirm the putative miR-149-3p-binding sites in ZEB1-AS1.

Results: Briefly, bioinformatics analysis inferred that ZEB1-AS1 interacts with miR-204, miR-610, and miR-149. Gain- or loss-of function assays suggested that ZEB1-AS1 negatively regulates miR-149-3p, miR-204-5p and miR-610 in GC cells. Validated by qPCR, ZEB1-AS1 was up-regulated and miR-149-3p down-regulated in GC cells and tissue. Data analyses indicated that ZEB1-AS1 and miR-149-3p are associated with the independent diagnosis and prognosis of GC. Functional assays support the theory that miR-149-3p hinders GC proliferation, migration and invasion, whereas its overexpression abrogates the corresponding effects induced by ZEB1-AS1. Lastly, dissection of the molecular mechanisms involved indicated that ZEB1-AS1 can regulate GC partly via a ZEB1-AS1/miR-149-3p axis.

Conclusions: ZEB1-AS1 can interact with specific miRNAs, forming a miRNA-mediated ceRNA network and promoting GC progress, partly through a ZEB1-AS1/miR-149-3p axis.

Citing Articles

LncRNA C2orf27A Promotes Gastric Cancer by Sponging MiR-610 and Elevating NOX4 Expression.

Zhuang M, Guo X, Lin D, Lin N, Wang X, Chen F J Cancer. 2025; 16(5):1504-1518.

PMID: 39991587 PMC: 11843226. DOI: 10.7150/jca.100621.

Comprehensive analysis of prognosis of patients with GBM based on 4 m6A-related lncRNAs and immune cell infiltration.

Luo Q, Yang Z, Deng R, Pang X, Han X, Liu X Heliyon. 2023; 9(2):e12838.

PMID: 36747529 PMC: 9898620. DOI: 10.1016/j.heliyon.2023.e12838.

Abnormally Expressed lncRNAs as Potential Biomarkers for Gastric Cancer Risk: A Diagnostic Meta-Bioinformatics Analysis.

Dong Y, Zhou Q, Li H, Lv Z, Yuan Y, Sun L Biomed Res Int. 2022; 2022:6712625.

PMID: 36389111 PMC: 9652703. DOI: 10.1155/2022/6712625.

Identification of Survival-Related Genes in Acute Myeloid Leukemia (AML) Based on Cytogenetically Normal AML Samples Using Weighted Gene Coexpression Network Analysis.

Chen T, Zhang J, Wang Y, Zhou H Dis Markers. 2022; 2022:5423694.

PMID: 36212177 PMC: 9537620. DOI: 10.1155/2022/5423694.

MicroRNA-149-3p expression correlates with outcomes of adrenocortical tumor patients and affects proliferation and cell cycle progression of H295A adrenocortical cancer cell line.

da Silva K, Veronez L, Correa C, Lira R, Baroni M, Silva Queiroz R Hum Cell. 2022; 35(6):1952-1960.

PMID: 36053456 DOI: 10.1007/s13577-022-00778-2.

References

He L, Hannon G . MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet. 2004; 5(7):522-31. DOI: 10.1038/nrg1379. View

Kang M, Ryu B, Lee M, Han J, Lee J, Ha T . NF-kappaB activates transcription of the RNA-binding factor HuR, via PI3K-AKT signaling, to promote gastric tumorigenesis. Gastroenterology. 2008; 135(6):2030-42, 2042.e1-3. DOI: 10.1053/j.gastro.2008.08.009. View

Bartel D . MicroRNAs: target recognition and regulatory functions. Cell. 2009; 136(2):215-33. PMC: 3794896. DOI: 10.1016/j.cell.2009.01.002. View

Ueda T, Volinia S, Okumura H, Shimizu M, Taccioli C, Rossi S . Relation between microRNA expression and progression and prognosis of gastric cancer: a microRNA expression analysis. Lancet Oncol. 2009; 11(2):136-46. PMC: 4299826. DOI: 10.1016/S1470-2045(09)70343-2. View

Ebert M, Sharp P . Emerging roles for natural microRNA sponges. Curr Biol. 2010; 20(19):R858-61. PMC: 4070712. DOI: 10.1016/j.cub.2010.08.052. View

Salmena L, Poliseno L, Tay Y, Kats L, Pandolfi P . A ceRNA hypothesis: the Rosetta Stone of a hidden RNA language?. Cell. 2011; 146(3):353-8. PMC: 3235919. DOI: 10.1016/j.cell.2011.07.014. View

Tay Y, Kats L, Salmena L, Weiss D, Tan S, Ala U . Coding-independent regulation of the tumor suppressor PTEN by competing endogenous mRNAs. Cell. 2011; 147(2):344-57. PMC: 3235920. DOI: 10.1016/j.cell.2011.09.029. View

Cesana M, Cacchiarelli D, Legnini I, Santini T, Sthandier O, Chinappi M . A long noncoding RNA controls muscle differentiation by functioning as a competing endogenous RNA. Cell. 2011; 147(2):358-69. PMC: 3234495. DOI: 10.1016/j.cell.2011.09.028. View

Karreth F, Tay Y, Perna D, Ala U, Tan S, Rust A . In vivo identification of tumor- suppressive PTEN ceRNAs in an oncogenic BRAF-induced mouse model of melanoma. Cell. 2011; 147(2):382-95. PMC: 3236086. DOI: 10.1016/j.cell.2011.09.032. View

10.

Wang J, Zhang J, Wu J, Luo D, Su K, Shi W . MicroRNA-610 inhibits the migration and invasion of gastric cancer cells by suppressing the expression of vasodilator-stimulated phosphoprotein. Eur J Cancer. 2011; 48(12):1904-13. DOI: 10.1016/j.ejca.2011.11.026. View

11.

Jiao X, Sherman B, Huang D, Stephens R, Baseler M, Lane H . DAVID-WS: a stateful web service to facilitate gene/protein list analysis. Bioinformatics. 2012; 28(13):1805-6. PMC: 3381967. DOI: 10.1093/bioinformatics/bts251. View

12.

Song S, Ajani J . The role of microRNAs in cancers of the upper gastrointestinal tract. Nat Rev Gastroenterol Hepatol. 2012; 10(2):109-18. PMC: 3855852. DOI: 10.1038/nrgastro.2012.210. View

13.

Song F, Yang D, Liu B, Guo Y, Zheng H, Li L . Integrated microRNA network analyses identify a poor-prognosis subtype of gastric cancer characterized by the miR-200 family. Clin Cancer Res. 2013; 20(4):878-89. DOI: 10.1158/1078-0432.CCR-13-1844. View

14.

Gala K, Chandarlapaty S . Molecular pathways: HER3 targeted therapy. Clin Cancer Res. 2014; 20(6):1410-6. PMC: 3977203. DOI: 10.1158/1078-0432.CCR-13-1549. View

15.

Karimi P, Islami F, Anandasabapathy S, Freedman N, Kamangar F . Gastric cancer: descriptive epidemiology, risk factors, screening, and prevention. Cancer Epidemiol Biomarkers Prev. 2014; 23(5):700-13. PMC: 4019373. DOI: 10.1158/1055-9965.EPI-13-1057. View

16.

Han T, Hur K, Xu G, Choi B, Okugawa Y, Toiyama Y . MicroRNA-29c mediates initiation of gastric carcinogenesis by directly targeting ITGB1. Gut. 2014; 64(2):203-14. PMC: 4384419. DOI: 10.1136/gutjnl-2013-306640. View

17.

Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M . Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2014; 136(5):E359-86. DOI: 10.1002/ijc.29210. View

18.

Chen F, Tian Y, Pang E, Wang Y, Li L . MALAT2-activated long noncoding RNA indicates a biomarker of poor prognosis in gastric cancer. Cancer Gene Ther. 2015; . DOI: 10.1038/cgt.2015.6. View

19.

Li P, Shan J, Chen X, Zhang D, Su L, Huang X . Epigenetic silencing of microRNA-149 in cancer-associated fibroblasts mediates prostaglandin E2/interleukin-6 signaling in the tumor microenvironment. Cell Res. 2015; 25(5):588-603. PMC: 4423088. DOI: 10.1038/cr.2015.51. View

20.

Li T, Xie J, Shen C, Cheng D, Shi Y, Wu Z . Upregulation of long noncoding RNA ZEB1-AS1 promotes tumor metastasis and predicts poor prognosis in hepatocellular carcinoma. Oncogene. 2015; 35(12):1575-84. DOI: 10.1038/onc.2015.223. View