miR‑210 promotes human osteosarcoma cell migration and invasion by targeting FGFRL1

Liu,Xiangjun; Zhang,Chengfeng; Wang,Cunhua; Sun,Jianwei; Wang,Deliang; Zhao,Yansheng; Xu,Xiaohui

doi:10.3892/ol.2018.8939

miR‑210 promotes human osteosarcoma cell migration and invasion by targeting FGFRL1

Authors:
- Xiangjun Liu
- Chengfeng Zhang
- Cunhua Wang
- Jianwei Sun
- Deliang Wang
- Yansheng Zhao
- Xiaohui Xu
View Affiliations

Affiliations: Department of Orthopedics, The People's Hospital of Qingdao West Coast New Area, Qingdao, Shandong 266400, P.R. China
Published online on: June 11, 2018 https://doi.org/10.3892/ol.2018.8939
Pages: 2229-2236

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

Osteosarcoma is a common bone tumor and a frequently occuring cancer‑associated threat to children. Notably, the prognosis of osteosarcoma is very poor when it is diagnosed with metastasis. A growing number of studies have indicated that various microRNAs (miRs) serve important regulatory roles in the pathogeny of different types of cancer. However, the functions of miR‑210 in osteosarcoma need to be elucidated comprehensively. The aim of the present study was to investigate the potential roles of miR‑210 in osteosarcoma by targeting fibroblast growth factor receptor‑like 1 (FGFRL1). Reverse transcription‑quantitative polymerase chain reaction results revealed that the expression of miR‑210 was highly elevated while FGFRL1 expression was reduced inversely in osteosarcoma tissues compared with matched normal tissues. The results of Transwell assays showed that miR‑210 promoted osteosarcoma cell migration and invasion. Furthermore, the luciferase reporter assay results suggested that miR‑210 could directly bind to FGFRL1 in osteosarcoma cells. In addition, the present findings demonstrated that miR‑210 could negatively regulate FGFRL1 expression by targeting the 3'untranslated region. In conclusion, the findings of the present study suggested that miR‑210 exerted tumor carcinogenic functions in osteosarcoma by targeting FGFRL1. The findings of this study demonstrated that FGFRL1 was a direct target of miR‑210 in osteosarcoma involved in the promoting functions mediated by miR‑210 in the invasion and migration of osteosarcoma, suggesting that miR‑210/FGFRL1 may be promising for discovering diagnostic and prognostic biomarkers for the therapies of osteosarcoma.

View Figures

View References

1	Angulo P, Kaushik G, Subramaniam D, Dandawate P, Neville K, Chastain K and Anant S: Natural compounds targeting major cell signaling pathways: A novel paradigm for osteosarcoma therapy. J Hematol Oncol. 10:102017. View Article : Google Scholar : PubMed/NCBI
2	Ferrari S and Serra M: An update on chemotherapy for osteosarcoma. Expert Opin Pharmacother. 16:2727–2736. 2015. View Article : Google Scholar : PubMed/NCBI
3	Isakoff MS, Bielack SS, Meltzer P and Gorlick R: Osteosarcoma: Current treatment and a collaborative pathway to success. J Clin Oncol. 33:3029–3035. 2015. View Article : Google Scholar : PubMed/NCBI
4	Chen Y, Xu SF, Xu M and Yu XC: Intentional marginal resection of periosteal osteosarcoma in combination with neoadjuvant chemotherapy: A report of two cases and a review of the literature. Oncol Lett. 13:1343–1347. 2017. View Article : Google Scholar : PubMed/NCBI
5	Hirotsu M, Setoguchi T, Sasaki H, Matsunoshita Y, Gao H, Nagao H, Kunigou O and Komiya S: Smoothened as a new therapeutic target for human osteosarcoma. Mol Cancer. 9:52010. View Article : Google Scholar : PubMed/NCBI
6	Margue C, Reinsbach S, Philippidou D, Beaume N, Walters C, Schneider JG, Nashan D, Behrmann I and Kreis S: Comparison of a healthy miRNome with melanoma patient miRNomes: Are microRNAs suitable serum biomarkers for cancer? Oncotarget. 6:12110–12127. 2015. View Article : Google Scholar : PubMed/NCBI
7	Guo K, Liang Z, Li F and Wang H: Comparison of miRNA and gene expression profiles between metastatic and primary prostate cancer. Oncol Lett. 14:6085–6090. 2017.PubMed/NCBI
8	Sun B, Liu X, Gao Y, Li L and Dong Z: Downregulation of miR-124 predicts poor prognosis in pancreatic ductal adenocarcinoma patients. Br J Biomed Sci. 73:152–307. 2016. View Article : Google Scholar : PubMed/NCBI
9	Ohzawa H, Miki A, Teratani T, Shiba S, Sakuma Y, Nishimura W, Noda Y, Fukushima N, Fujii H, Hozumi Y, et al: Usefulness of miRNA profiles for predicting pathological responses to neoadjuvant chemotherapy in patients with human epidermal growth factor receptor 2-positive breast cancer. Oncol Lett. 13:1731–1740. 2017. View Article : Google Scholar : PubMed/NCBI
10	Gee HE, Ivan C, Calin GA and Ivan M: HypoxamiRs and cancer: From biology to targeted therapy. Antioxid Redox Signal. 21:1220–1238. 2014. View Article : Google Scholar : PubMed/NCBI
11	Manikandan J, Aarthi JJ, Kumar SD and Pushparaj PN: Oncomirs: The potential role of non-coding microRNAs in understanding cancer. Bioinformation. 2:330–334. 2008. View Article : Google Scholar : PubMed/NCBI
12	Paudel D, Zhou W, Ouyang Y, Dong S, Huang Q, Giri R, Wang J and Tong X: MicroRNA-130b functions as a tumor suppressor by regulating RUNX3 in epithelial ovarian cancer. Gene. 586:48–55. 2016. View Article : Google Scholar : PubMed/NCBI
13	Zhuang LK, Yang YT, Ma X, Han B, Wang ZS, Zhao QY, Wu LQ and Qu ZQ: MicroRNA-92b promotes hepatocellular carcinoma progression by targeting Smad7 and is mediated by long non-coding RNA XIST. Cell Death Dis. 7:e22032016. View Article : Google Scholar : PubMed/NCBI
14	Wu D, Huang P, Wang L, Zhou Y, Pan H and Qu P: MicroRNA-143 inhibits cell migration and invasion by targeting matrix metalloproteinase 13 in prostate cancer. Mol Med Rep. 8:626–630. 2013. View Article : Google Scholar : PubMed/NCBI
15	Zhang S, Lai N, Liao K, Sun J and Lin Y: MicroRNA-210 regulates cell proliferation and apoptosis by targeting regulator of differentiation 1 in glioblastoma cells. Folia Neuropathol. 53:236–244. 2015. View Article : Google Scholar : PubMed/NCBI
16	Liu D, Xia H, Wang F, Chen C and Long J: MicroRNA-210 interacts with FBXO31 to regulate cancer proliferation cell cycle and migration in human breast cancer. Onco Targets Ther. 9:5245–5255. 2016. View Article : Google Scholar : PubMed/NCBI
17	Amponsah PS, Fan P, Bauer N, Zhao Z, Gladkich J, Fellenberg J and Herr I: microRNA-210 overexpression inhibits tumor growth and potentially reverses gemcitabine resistance in pancreatic cancer. Cancer Lett. 388:107–117. 2017. View Article : Google Scholar : PubMed/NCBI
18	Trueb B: Biology of FGFRL1, the fifth fibroblast growth factor receptor. Cell Mol Life Sci. 68:951–964. 2011. View Article : Google Scholar : PubMed/NCBI
19	Zhuang L, Karotki AV, Bruecker P and Trueb B: Comparison of the receptor FGFRL1 from sea urchins and humans illustrates evolution of a zinc binding motif in the intracellular domain. BMC Biochem. 10:332009. View Article : Google Scholar : PubMed/NCBI
20	Kähkönen TE, Ivaska KK, Jian M, Büki KG, Väänänen HK and Härkönen PL: Role of fibroblast growth factor receptors (FGFR) and FGFR like-1 (FGFRL1) in mesenchymal stromal cell differentiation to osteoblasts and adipocytes. Mol Cell Endocrinol. 461:194–204. 2018. View Article : Google Scholar : PubMed/NCBI
21	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
22	Sun Z, Liu Q, Hong H, Zhang H and Zhang T: miR-19 promotes osteosarcoma progression by targeting SOCS6. Biochem Biophys Res Commun. 495:1363–1369. 2018. View Article : Google Scholar : PubMed/NCBI
23	Urciuoli E, Coletta I, Rizzuto E, De Vito R, Petrini S, D'Oria V, Pezzullo M, Milano GM, Cozza R, Locatelli F and Peruzzi B: Src nuclear localization and its prognostic relevance in human osteosarcoma. J Cell Physiol. 233:1658–1670. 2018. View Article : Google Scholar : PubMed/NCBI
24	Wang D, Song Z and Wang Z: Common mechanism of pathogenesis in various types of metastatic osteosarcoma. Oncol Lett. 14:6307–6313. 2017.PubMed/NCBI
25	Luo T, Yi X and Si W: Identification of miRNA and genes involving in osteosarcoma by comprehensive analysis of microRNA and copy number variation data. Oncol Lett. 14:5427–5433. 2017.PubMed/NCBI
26	Diao H, Liu B, Shi Y, Song C, Guo Z, Liu N, Song X, Lu Y, Lin X and Li Z: MicroRNA-210 alleviates oxidative stress-associated cardiomyocyte apoptosis by regulating BNIP3. Biosci Biotechnol Biochem. 81:1712–1720. 2017. View Article : Google Scholar : PubMed/NCBI
27	Wang Z, Deng M, Liu Z and Wu S: Hypoxia-induced miR-210 promoter demethylation enhances proliferation, autophagy and angiogenesis of schwannoma cells. Oncol Rep. 37:3010–3018. 2017. View Article : Google Scholar : PubMed/NCBI
28	Li Y, Yang C, Zhang L and Yang P: MicroRNA-210 induces endothelial cell apoptosis by directly targeting PDK1 in the setting of atherosclerosis. Cell Mol Biol Lett. 22:32017. View Article : Google Scholar : PubMed/NCBI
29	Yang X, Shi L, Yi C, Yang Y, Chang L and Song D: MiR-210-3p inhibits the tumor growth and metastasis of bladder cancer via targeting fibroblast growth factor receptor-like 1. Am J Cancer Res. 7:1738–1753. 2017.PubMed/NCBI
30	Ruan K, Song G and Ouyang G: Role of hypoxia in the hallmarks of human cancer. J Cell Biochem. 107:1053–1062. 2009. View Article : Google Scholar : PubMed/NCBI
31	Arvelo F and Cotte C: Hypoxia in cancer malignity. Review. Invest Clin. 50:529–546. 2009.(In Spanish). PubMed/NCBI
32	Qin Q, Furong W and Baosheng L: Multiple functions of hypoxia-regulated miR-210 in cancer. J Exp Clin Cancer Res. 33:502014. View Article : Google Scholar : PubMed/NCBI
33	Beenken A and Mohammadi M: The FGF family: Biology, pathophysiology and therapy. Nat Rev Drug Discov. 8:235–253. 2009. View Article : Google Scholar : PubMed/NCBI
34	Zhou WY, Zheng H, Du XL and Yang JL: Characterization of FGFR signaling pathway as therapeutic targets for sarcoma patients. Cancer Biol Med. 13:260–278. 2016. View Article : Google Scholar : PubMed/NCBI
35	Zhuang L, Steinberg F and Trueb B: Receptor FGFRL1 acts as a tumor suppressor in nude mice when overexpressed in HEK 293 Tet-On cells. Oncol Lett. 12:4524–4530. 2016. View Article : Google Scholar : PubMed/NCBI
36	Yang X, Steinberg F, Zhuang L, Bessey R and Trueb B: Receptor FGFRL1 does not promote cell proliferation but induces cell adhesion. Int J Mol Med. 38:30–38. 2016. View Article : Google Scholar : PubMed/NCBI