MicroRNA‑885‑5p promotes osteosarcoma proliferation and migration by downregulation of cell division cycle protein 73 homolog expression

Yu,Feng‑Qiang; Wang,Zeng; Wang,Xin‑Wen; Wang,Sheng‑Lin; Li,Xiao‑Dong; Huang,Qing‑Shan; Lin,Jian‑Hua

doi:10.3892/ol.2018.9802

MicroRNA‑885‑5p promotes osteosarcoma proliferation and migration by downregulation of cell division cycle protein 73 homolog expression

Authors:
- Feng‑Qiang Yu
- Zeng Wang
- Xin‑Wen Wang
- Sheng‑Lin Wang
- Xiao‑Dong Li
- Qing‑Shan Huang
- Jian‑Hua Lin
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Affiliations: Department of Orthopedics, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, P.R. China, Central Laboratory, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, P.R. China
Published online on: December 6, 2018 https://doi.org/10.3892/ol.2018.9802
Pages: 1565-1572
Copyright: © Yu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Osteosarcoma (OS) is the most common primary malignant bone tumor. Numerous studies have strongly implicated the ectopic expression of microRNAs (miRNAs/miRs), including miR‑885‑5p, which is aberrantly expressed in several cancer types, in multiple cancer‑related processes. However, the role of miR‑885‑5p in OS remains unknown. In the present study, it was found that the expression of miR‑885‑5p was markedly upregulated in OS cell lines and clinical tissues. Moreover, high expression of miR‑885‑5p was significantly associated with the development of OS. The human OS MG‑63 cell line was transfected with recombinant lentivirus to regulate miR‑885‑5p expression. Overexpressed miR‑885‑5p significantly promoted the proliferation and migration of MG‑63 cells in vitro, while downregulating miR‑885‑5p expression reversed these effects. Furthermore, bioinformatic analysis was used to predict the potential target genes of miR‑885‑5p, and cell division cycle protein 73 homolog (CDC73) was identified as a novel and direct target of miR‑885‑5p. This interaction was further confirmed using reverse transcription‑quantitative polymerase chain reaction, western blotting and luciferase activity assays. These findings suggest that miR‑885‑5p serves a critical role in facilitating OS proliferation and migration, and can regulate CDC73 expression in OS cells and tissues. Thus, miR‑885‑5p could be a promising novel therapeutic biomarker for OS.

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1	Kobayashi E, Hornicek FJ and Duan Z: MicroRNA involvement in osteosarcoma. Sarcoma. 2012:3597392012. View Article : Google Scholar : PubMed/NCBI
2	Mirabello L, Troisi RJ and Savage SA: Osteosarcoma incidence and survival rates from 1973 to 2004: Data from the surveillance, epidemiology, and end results program. Cancer. 115:1531–1543. 2009. View Article : Google Scholar : PubMed/NCBI
3	Ottaviani G and Jaffe N: The epidemiology of osteosarcoma. Cancer Treat Res. 152:3–13. 2009. View Article : Google Scholar : PubMed/NCBI
4	Marina N, Gebhardt M, Teot L and Gorlick R: Biology and therapeutic advances for pediatric osteosarcoma. Oncologist. 9:422–441. 2004. View Article : Google Scholar : PubMed/NCBI
5	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
6	Zamore PD and Haley B: Ribo-gnome: The big world of small RNAs. Science. 309:1519–1524. 2005. View Article : Google Scholar : PubMed/NCBI
7	Shin C, Nam JW, Farh KK, Chiang HR, Shkumatava A and Bartel DP: Expanding the microRNA targeting code: Functional sites with centered pairing. Mol Cell. 38:789–802. 2010. View Article : Google Scholar : PubMed/NCBI
8	Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, Shimizu M, Rattan S, Bullrich F, Negrini M and Croce CM: Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci USA. 101:2999–3004. 2004. View Article : Google Scholar : PubMed/NCBI
9	Qin S, Ai F, Ji WF, Rao W, Zhang HC and Yao WJ: miR-19a promotes cell growth and tumorigenesis through targeting SOCS1 in gastric cancer. Asian Pac J Cancer Prev. 14:835–840. 2013. View Article : Google Scholar : PubMed/NCBI
10	Jones KB, Salah Z, Del Mare S, Galasso M, Gaudio E, Nuovo GJ, Lovat F, LeBlanc K, Palatini J, Randall RL, et al: miRNA signatures associate with pathogenesis and progression of osteosarcoma. Cancer Res. 72:1865–1877. 2012. View Article : Google Scholar : PubMed/NCBI
11	Lam CS, Ng L, Chow AK, Wan TM, Yau S, Cheng NS, Wong SK, Man JH, Lo OS, Foo DC, et al: Identification of microRNA 885-5p as a novel regulator of tumor metastasis by targeting CPEB2 in colorectal cancer. Oncotarget. 8:26858–26870. 2017. View Article : Google Scholar : PubMed/NCBI
12	Yoshino H, Yonemori M, Miyamoto K, Tatarano S, Kofuji S, Nohata N, Nakagawa M and Enokida H: microRNA-210-3p depletion by CRISPR/Cas9 promoted tumorigenesis through revival of TWIST1 in renal cell carcinoma. Oncotarget. 8:20881–20894. 2017. View Article : Google Scholar : PubMed/NCBI
13	Petric R, Gazic B, Goricar K, Dolzan V, Dzodic R and Besic N: Expression of miRNA and occurrence of distant metastases in patients with Hürthle cell carcinoma. Int J Endocrinol. 2016:89452472016. View Article : Google Scholar : PubMed/NCBI
14	Zhang Z, Yin J, Yang J, Shen W, Zhang C, Mou W, Luo J, Yan H, Sun P, Luo Y, et al: miR-885-5p suppresses hepatocellular carcinoma metastasis and inhibits Wnt/β-catenin signaling pathway. Oncotarget. 7:75038–75051. 2016.PubMed/NCBI
15	Allen-Rhoades W, Kurenbekova L, Satterfield L, Parikh N, Fuja D, Shuck RL, Rainusso N, Trucco M, Barkauskas DA, Jo E, et al: Cross-species identification of a plasma microRNA signature for detection, therapeutic monitoring, and prognosis in osteosarcoma. Cancer Med. 4:977–988. 2015. View Article : Google Scholar : PubMed/NCBI
16	Zhao G, Cai C, Yang T, Qiu X, Liao B, Li W, Ji Z, Zhao J, Zhao H, Guo M, et al: MicroRNA-221 induces cell survival and cisplatin resistance through PI3K/Akt pathway in human osteosarcoma. PLoS One. 8:e539062013. View Article : Google Scholar : PubMed/NCBI
17	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
18	Shi K, Lan RL, Tao X, Wu CY, Hong HF and Lin JH: Vitronectin significantly influences prognosis in osteosarcoma. Int J Clin Exp Pathol. 8:11364–11371. 2015.PubMed/NCBI
19	Enneking WF, Spanier SS and Goodman MA: A system for the surgical staging of musculoskeletal sarcoma. Clin Orthop Relat Res. 106–120. 1980.PubMed/NCBI
20	Han K, Zhao T, Chen X, Bian N, Yang T, Ma Q, Cai C, Fan Q, Zhou Y and Ma B: microRNA-194 suppresses osteosarcoma cell proliferation and metastasis in vitro and in vivo by targeting CDH2 and IGF1R. Int J Oncol. 45:1437–1449. 2014. View Article : Google Scholar : PubMed/NCBI
21	Arndt CA, Rose PS, Folpe AL and Laack NN: Common musculoskeletal tumors of childhood and adolescence. Mayo Clin Proc. 87:475–487. 2012. View Article : Google Scholar : PubMed/NCBI
22	Nelson KM and Weiss GJ: MicroRNAs and cancer: Past, present, and potential future. Mol Cancer Ther. 7:3655–3660. 2008. View Article : Google Scholar : PubMed/NCBI
23	Zhu SW, Li JP, Ma XL, Ma JX, Yang Y, Chen Y and Liu W: miR-9 modulates osteosarcoma cell growth by targeting the gcip tumor suppressor. Asian Pac J Cancer Prev. 16:4509–4513. 2015. View Article : Google Scholar : PubMed/NCBI
24	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
25	Kawano M, Tanaka K, Itonaga I, Ikeda S, Iwasaki T and Tsumura H: microRNA-93 promotes cell proliferation via targeting of PTEN in Osteosarcoma cells. J Exp Clin Cancer Res. 34:762015. View Article : Google Scholar : PubMed/NCBI
26	Ma C, Zhan C, Yuan H, Cui Y and Zhang Z: MicroRNA-603 functions as an oncogene by suppressing BRCC2 protein translation in osteosarcoma. Oncol Rep. 35:3257–3264. 2016. View Article : Google Scholar : PubMed/NCBI
27	Xu JF, Yang GH, Pan XH, Zhang SJ, Zhao C, Qiu BS, Gu HF, Hong JF, Cao L, Chen Y, et al: Altered microRNA expression profile in exosomes during osteogenic differentiation of human bone marrow-derived mesenchymal stem cells. PLoS One. 9:e1146272014. View Article : Google Scholar : PubMed/NCBI
28	Wagner ER, Luther G, Zhu G, Luo Q, Shi Q, Kim SH, Gao JL, Huang E, Gao Y, Yang K, et al: Defective osteogenic differentiation in the development of osteosarcoma. Sarcoma. 2011:3252382011. View Article : Google Scholar : PubMed/NCBI
29	Carpten JD, Robbins CM, Villablanca A, Forsberg L, Presciuttini S, Bailey-Wilson J, Simonds WF, Gillanders EM, Kennedy AM, Chen JD, et al: HRPT2, encoding parafibromin, is mutated in hyperparathyroidism-jaw tumor syndrome. Nat Genet. 32:676–680. 2002. View Article : Google Scholar : PubMed/NCBI
30	Shattuck TM, Välimäki S, Obara T, Gaz RD, Clark OH, Shoback D, Wierman ME, Tojo K, Robbins CM, Carpten JD, et al: Somatic and germ-line mutations of the HRPT2 gene in sporadic parathyroid carcinoma. N Engl J Med. 349:1722–1729. 2003. View Article : Google Scholar : PubMed/NCBI
31	Zhao J, Yart A, Frigerio S, Perren A, Schraml P, Weisstanner C, Stallmach T, Krek W and Moch H: Sporadic human renal tumors display frequent allelic imbalances and novel mutations of the HRPT2 gene. Oncogene. 26:3440–3449. 2007. View Article : Google Scholar : PubMed/NCBI
32	Zhang C, Kong D, Tan MH, Pappas DL Jr, Wang PF, Chen J, Farber L, Zhang N, Koo HM, Weinreich M, et al: Parafibromin inhibits cancer cell growth and causes G1 phase arrest. Biochem Biophys Res Commun. 350:17–24. 2006. View Article : Google Scholar : PubMed/NCBI
33	James RG, Biechele TL, Conrad WH, Camp ND, Fass DM, Major MB, Sommer K, Yi X, Roberts BS, Cleary MA, et al: Bruton's tyrosine kinase revealed as a negative regulator of Wnt-beta-catenin signaling. Sci Signal. 2:ra252009. View Article : Google Scholar : PubMed/NCBI
34	Selbach M, Schwanhäusser B, Thierfelder N, Fang Z, Khanin R and Rajewsky N: Widespread changes in protein synthesis induced by microRNAs. Nature. 455:58–63. 2008. View Article : Google Scholar : PubMed/NCBI