EPEL promotes the migration and invasion of osteosarcoma cells by upregulating ROCK1

Chen,Shunguang; Liu,Zhengjie; Lu,Shengjun; Hu,Biao

doi:10.3892/ol.2019.9975

EPEL promotes the migration and invasion of osteosarcoma cells by upregulating ROCK1

Authors:
- Shunguang Chen
- Zhengjie Liu
- Shengjun Lu
- Biao Hu
View Affiliations

Affiliations: Department of Orthopaedics, Jingzhou Central Hospital, Jingzhou, Hubei 434020, P.R. China
Published online on: January 25, 2019 https://doi.org/10.3892/ol.2019.9975
Pages: 3133-3140
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

E2F‑mediated cell proliferation enhancing long non‑coding RNA (lncRNA) (EPEL) is a newly identified lncRNA involved in the regulation of lung cancer cell proliferation. However, its association with other types of cancer is unknown. The present study recruited patients with osteosarcoma and healthy controls. Tumor and adjacent healthy tissues were obtained from patients with osteosarcoma, and whole blood was extracted from patients and healthy controls. The expression levels of EPEL in tissues were detected by reverse transcription‑quantitative polymerase chain reaction. The diagnostic value of serum EPEL for osteosarcoma was evaluated by receiver operating characteristic curve analysis. The association between serum levels of EPEL and basic clinical patient information was analyzed by χ2 test. Subsequently, EPEL overexpression in osteosarcoma cell lines was established, and its effects on cell migration and invasion were explored by Transwell assay. The implications of EPEL overexpression on Rho‑associated coiled‑coil containing protein kinase 1 (ROCK1) expression were investigated by western blotting. The results revealed that EPEL was upregulated in tumor tissues compared with adjacent tissues. In addition, serum levels of EPEL were higher in patients with osteosarcoma compared with healthy controls, and were positively associated with distant tumor metastasis. Furthermore, EPEL overexpression promoted the migration and invasion of osteosarcoma cells and induced overexpression of ROCK1. In conclusion, these results suggested that EPEL may promote the migration and invasion of osteosarcoma cells by upregulating ROCK1.

View Figures

View References

1	Botter SM, Neri D and Fuchs B: Recent advances in osteosarcoma. Curr Opin Pharmacol. 16:15–23. 2014. View Article : Google Scholar : PubMed/NCBI
2	Gattia M, Solari A, Pattarozzi A, Campanella C, Thellung S, Maniscalco L, De Maria R, Würth R, Corsaro A, Bajetto A, et al: In vitro and in vivo characterization of stem-like cells from canine osteosarcoma and assessment of drug sensitivity. Exp Cell Res. 363:48–64. 2018. View Article : Google Scholar : PubMed/NCBI
3	Bielack SS, Kempf-Bielack B, Delling G, Exner GU, Flege S, Helmke K, Kotz R, Salzer-Kuntschik M, Werner M, Winkelmann W, et al: Prognostic factors in high-grade osteosarcoma of the extremities or trunk: An analysis of 1,702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols. J Clin Oncol. 20:776–790. 2002. View Article : Google Scholar : PubMed/NCBI
4	Luetke A, Meyers PA, Lewis I and Juergens H: Osteosarcoma treatment-where do we stand? A state of the art review. Cancer Treat Rev. 40:523–532. 2014. View Article : Google Scholar : PubMed/NCBI
5	Kansara M and Thomas DM: Molecular pathogenesis of osteosarcoma. DNA Cell Biol. 26:1–18. 2007. View Article : Google Scholar : PubMed/NCBI
6	Li JP, Liu LH, Li J, Chen Y, Jiang XW, Ouyang YR, Liu YQ, Zhong H, Li H and Xiao T: Microarray expression profile of long noncoding RNAs in human osteosarcoma. Biochem Biophys Res Commun. 433:200–206. 2013. View Article : Google Scholar : PubMed/NCBI
7	Gao JZ, Li J, DU JL and Li XL: Long non-coding RNA HOTAIR is a marker for hepatocellular carcinoma progression and tumor recurrence. Oncol Lett. 11:1791–1798. 2016. View Article : Google Scholar : PubMed/NCBI
8	Ning S, Zhang J, Wang P, Zhi H, Wang J, Liu Y, Gao Y, Guo M, Yue M, Wang L and Li X: Lnc2Cancer: A manually curated database of experimentally supported lncRNAs associated with various human cancers. Nucleic Acids Res. 44:D980–D985. 2016. View Article : Google Scholar : PubMed/NCBI
9	Augoff K, McCue B, Plow EF and Sossey-Alaoui K: miR-31 and its host gene lncRNA LOC554202 are regulated by promoter hypermethylation in triple-negative breast cancer. Mol Cancer. 11:52012. View Article : Google Scholar : PubMed/NCBI
10	Wang Y, Zhao W and Fu Q: miR-335 suppresses migration and invasion by targeting ROCK1 in osteosarcoma cells. Mol Cell Biochem. 384:105–111. 2013. View Article : Google Scholar : PubMed/NCBI
11	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
12	Harting MT, Blakely ML, Jaffe N, Cox CS Jr, Hayes-Jordan A, Benjamin RS, Raymond AK, Andrassy RJ and Lally KP: Long-term survival after aggressive resection of pulmonary metastases among children and adolescents with osteosarcoma. J Pediatr Surg. 41:194–199. 2006. View Article : Google Scholar : PubMed/NCBI
13	Hori SS and Gambhir SS: Mathematical model identifies blood biomarker-based early cancer detection strategies and limitations. Sci Transl Med. 3:109ra–116ra. 2011. View Article : Google Scholar
14	Grammatikakis I, Panda AC, Abdelmohsen K and Gorospe M: Long noncoding RNAs (lncRNAs) and the molecular hallmarks of aging. Aging (Albany NY). 6:992–1009. 2014. View Article : Google Scholar : PubMed/NCBI
15	Mayfield RD: Emerging roles for ncRNAs in alcohol use disorders. Alcohol. 60:31–39. 2017. View Article : Google Scholar : PubMed/NCBI
16	Wang J, Qiu M, Xu Y, Li M, Dong G, Mao Q, Yin R and Xu L: Long noncoding RNA CCAT2 correlates with smoking in esophageal squamous cell carcinoma. Tumour Biol. 36:5523–5528. 2015. View Article : Google Scholar : PubMed/NCBI
17	Rath N and Olson MF: Rho-associated kinases in tumorigenesis: Re-considering ROCK inhibition for cancer therapy. EMBO Rep. 13:900–908. 2012. View Article : Google Scholar : PubMed/NCBI
18	Zhou X, Wei M and Wang W: MicroRNA-340 suppresses osteosarcoma tumor growth and metastasis by directly targeting ROCK1. Biochem Biophys Res Commun. 437:653–658. 2013. View Article : Google Scholar : PubMed/NCBI
19	Liu X, Choy E, Hornicek FJ, Yang S, Yang C, Harmon D, Mankin H and Duan Z: ROCK1 as a potential therapeutic target in osteosarcoma. J Orthop Res. 29:1259–1266. 2011. View Article : Google Scholar : PubMed/NCBI
20	Li E, Zhang J, Yuan T and Ma B: MiR-145 inhibits osteosarcoma cells proliferation and invasion by targeting ROCK1. Tumour Biol. 35:7645–7650. 2014. View Article : Google Scholar : PubMed/NCBI