MicroRNA profiling and bioinformatics analyses reveal the potential roles of microRNAs in chordoma

Chen,Kangwu; Chen,Hao; Zhang,Kai; Sun,Siwei; Mo,Jianqiang; Lu,Jian; Qian,Zhonglai; Yang,Huilin

doi:10.3892/ol.2017.6839

MicroRNA profiling and bioinformatics analyses reveal the potential roles of microRNAs in chordoma

Authors:
- Kangwu Chen
- Hao Chen
- Kai Zhang
- Siwei Sun
- Jianqiang Mo
- Jian Lu
- Zhonglai Qian
- Huilin Yang
View Affiliations

Affiliations: Department of Orthopedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China
Published online on: August 28, 2017 https://doi.org/10.3892/ol.2017.6839
Pages: 5533-5539

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

Chordoma is a rare aggressive bone tumor arising from remnants of the notochord, and patients with chordoma have a poor prognosis. However, the unique expression profiles of microRNAs (miRNAs/miRs) and their downstream signaling pathways in chordoma remain incompletely characterized. The aim of the present study was to delineate the global miRNA expression profile and associated signaling networks in chordoma. miRNA profiling was performed on chordoma and fetal notochord tissues. Differentially expressed miRNAs in chordoma were analyzed using microarrays with hierarchical clustering analysis. The target genes of the differentially expressed miRNAs were predicted, and Gene Ontology (GO) and pathway analyses were performed for the intersecting genes. A total of 42 miRNAs were significantly dysregulated in chordoma compared with that in fetal nucleus pulposus tissues. The expression of hsa‑miR‑21‑3p, hsa‑miR‑150‑5p, hsa‑miR‑1290 and hsa‑miR‑623 were validated using the reverse transcription‑quantitative polymerase chain reaction. On the basis of the intersection predicted by three databases (Targetscan, microRNA.org and PITA), 10,292 potential miRNA targets were identified. Bioinformatic analyses suggested that these dysregulated miRNAs and their predicted targets were functions of signaling pathways in cancer, the mitogen‑activated protein kinase signaling pathway, regulation of actin cytoskeleton, focal adhesion and endocytosis. In particular, human (hsa‑)miR‑185‑5p was identified as a crucial miRNA in chordoma development via the Wnt signaling pathway. The results of the present study provide a comprehensive expression and functional profile of differentially expressed miRNAs associated with chordoma. This profile may serve as a potential tool for biomarker and therapeutic target identification in patients with chordoma.

View Figures

View References

1	Casali PG, Stacchiotti S, Sangalli C, Olmi P and Gronchi A: Chordoma. Curr Opin Oncol. 19:367–370. 2007. View Article : Google Scholar : PubMed/NCBI
2	McMaster ML, Goldstein AM, Bromley CM, Ishibe N and Parry DM: Chordoma: Incidence and survival patterns in the United States, 1973–1995. Cancer Causes Control. 12:1–11. 2001. View Article : Google Scholar : PubMed/NCBI
3	Fuchs B, Dickey ID, Yaszemski MJ, Inwards CY and Sim FH: Operative management of sacral chordoma. J Bone Joint Surg Am. 87:2211–2216. 2005. View Article : Google Scholar : PubMed/NCBI
4	Sciubba DM, Cheng JJ, Petteys RJ, Weber KL, Frassica DA and Gokaslan ZL: Chordoma of the sacrum and vertebral bodies. J Am Acad Orthop Surg. 17:708–717. 2009. View Article : Google Scholar : PubMed/NCBI
5	Chugh R, Tawbi H, Lucas DR, Biermann JS, Schuetze SM and Baker LH: Chordoma: The nonsarcoma primary bone tumor. Oncologist. 12:1344–1350. 2007. View Article : Google Scholar : PubMed/NCBI
6	Lujambio A and Lowe SW: The microcosmos of cancer. Nature. 482:347–355. 2012. View Article : Google Scholar : PubMed/NCBI
7	Kong YW, Ferland-McCollough D, Jackson TJ and Bushell M: microRNAs in cancer management. Lancet Oncol. 13:e249–e258. 2012. View Article : Google Scholar : PubMed/NCBI
8	Duan Z, Choy E, Nielsen GP, Rosenberg A, Iafrate J, Yang C, Schwab J, Mankin H, Xavier R and Hornicek FJ: Differential expression of microRNA (miRNA) in chordoma reveals a role for miRNA-1 in Met expression. J Orthop Res. 28:746–752. 2010.PubMed/NCBI
9	Bayrak OF, Gulluoglu S, Aydemir E, Ture U, Acar H, Atalay B, Demir Z, Sevli S, Creighton CJ, Ittmann M, et al: MicroRNA expression profiling reveals the potential function of microRNA-31 in chordomas. J Neurooncol. 115:143–151. 2013. View Article : Google Scholar : PubMed/NCBI
10	Zhang Y, Schiff D, Park D and Abounader R: MicroRNA-608 and microRNA-34a regulate chordoma malignancy by targeting EGFR, Bcl-xL and MET. PLoS One. 9:e915462014. View Article : Google Scholar : PubMed/NCBI
11	Vujovic S, Henderson S, Presneau N, Odell E, Jacques TS, Tirabosco R, Boshoff C and Flanagan AM: Brachyury, a crucial regulator of notochordal development, is a novel biomarker for chordomas. J Pathol. 209:157–165. 2006. View Article : Google Scholar : PubMed/NCBI
12	Shen J, Shi Q, Lu J, Wang DL, Zou TM, Yang HL and Zhu GQ: Histological study of chordomaorigin from fetal notochordal cell rests. Spine (Phila Pa 1976). 38:2165–2170. 2013. View Article : Google Scholar : PubMed/NCBI
13	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
14	Ziyan W, Shuhua Y, Xiufang W and Xiaoyun L: MicroRNA-21 is involved in osteosarcoma cell invasion and migration. Med Oncol. 28:1469–1474. 2011. View Article : Google Scholar : PubMed/NCBI
15	Zhang C, Liu K, Li T, Fang J, Ding Y, Sun L, Tu T, Jiang X, Du S, Hu J, et al: miR-21: A gene of dual regulation in breast cancer. Int J Oncol. 48:161–172. 2016. View Article : Google Scholar : PubMed/NCBI
16	Basati G, Razavi Emami A, Abdi S and Mirzaei A: Elevated level of microRNA-21 in the serum of patients with colorectal cancer. Med Oncol. 31:2052014. View Article : Google Scholar : PubMed/NCBI
17	Long C, Jiang L, Wei F, Ma C, Zhou H, Yang S, Liu X and Liu Z: Integrated miRNA-mRNA analysis revealing the potential roles of miRNAs in chordomas. PLoS One. 8:e666762013. View Article : Google Scholar : PubMed/NCBI
18	Tamborini E, Virdis E, Negri T, Orsenigo M, Brich S, Conca E, Gronchi A, Stacchiotti S, Manenti G, Casali PG, et al: Analysis of receptor tyrosine kinases (RTKs) and downstream pathways in chordomas. Neuro Oncol. 12:776–789. 2010. View Article : Google Scholar : PubMed/NCBI
19	Zhang K, Chen H, Zhang B, Sun J, Lu J, Chen K and Yang H: Overexpression of Raf-1 and ERK1/2 in sacral chordoma and association with tumor recurrence. Int J Clin Exp Pathol. 8:608–614. 2015.PubMed/NCBI
20	Tian J, He H and Lei G: Wnt/β-catenin pathway in bone cancers. Tumour Biol. 35:9439–9445. 2014. View Article : Google Scholar : PubMed/NCBI
21	Song JL, Nigam P, Tektas SS and Selva E: microRNA regulation of Wnt signaling pathways in development and disease. Cell Signal. 27:1380–1391. 2015. View Article : Google Scholar : PubMed/NCBI
22	Li G, Wang Y, Liu Y, Su Z, Liu C, Ren S, Deng T, Huang D, Tian Y and Qiu Y: miR-185-3p regulates nasopharyngeal carcinoma radioresistance by targeting WNT2B in vitro. Cancer Sci. 105:1560–1568. 2014. View Article : Google Scholar : PubMed/NCBI
23	Liu M, Lang N, Chen X, Tang Q, Liu S, Huang J, Zheng Y and Bi F: miR-185 targets RhoA and Cdc42 expression and inhibits the proliferation potential of human colorectal cells. Cancer Lett. 301:151–160. 2011. View Article : Google Scholar : PubMed/NCBI
24	Fu P, Du F, Yao M, Lv K and Liu Y: MicroRNA-185 inhibits proliferation by targeting c-Met in human breast cancer cells. Exp Ther Med. 8:1879–1883. 2014.PubMed/NCBI