microRNA‑625 targets Yes‑associated protein 1 to suppress cell proliferation and invasion of osteosarcoma

Luo,Zheng; Wu,Gang; Zhang,Daiyang; Liu,Jun; Ran,Renguo

doi:10.3892/mmr.2017.8079

microRNA‑625 targets Yes‑associated protein 1 to suppress cell proliferation and invasion of osteosarcoma

Authors:
- Zheng Luo
- Gang Wu
- Daiyang Zhang
- Jun Liu
- Renguo Ran
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Affiliations: Department of Spinal Surgery, The Central Hospital of Enshi Autonomous Prefecture, Enshi, Hubei 445000, P.R. China, Department of Inspection, The Central Hospital of Enshi Autonomous Prefecture, Enshi, Hubei 445000, P.R. China
Published online on: November 15, 2017 https://doi.org/10.3892/mmr.2017.8079
Pages: 2005-2011

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Abstract

Osteosarcoma (OS) is the leading cause of cancer‑associated mortality in adolescents and children. MicroRNAs (miRNAs) have critical roles in cancer, particularly in the initiation and progression of OS. Therefore, OS‑associated miRNAs should be identified for use as therapeutic targets for treatment of OS. This study aimed to investigate the expression pattern, potential roles and underlying mechanism of microRNA‑625 (miR‑625) in OS. miR‑625 was markedly downregulated in OS tissues and cell lines compared with that in associated adjacent non‑tumor tissues and human normal osteoblasts, respectively. The enforced expression of miR‑625 using miRNA mimics significantly reduced the proliferation and invasion of OS cells. Bioinformatics analysis and luciferase reporter assays indicated that miR‑625 targeted the 3'‑untranslated region of Yes‑associated protein 1 (YAP‑1). Furthermore, upregulation of miR‑625 reduced endogenous YAP1 expression at the mRNA and protein levels. The upregulated expression of YAP1 in OS tissues was inversely correlated with miR‑625 expression. YAP1 restoration using a recombinant plasmid rescued the miR‑625‑mediated tumor‑suppressive effects in OS cells. In conclusion, miR‑625 attenuated the cell proliferation and invasion of OS by suppressing YAP1. Thus, miR‑625 may be a potential target for OS therapy.

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1	Guillon MA, Mary PM, Brugière L, Marec-Bérard P, Pacquement HD, Schmitt C, Guinebretière JM and Tabone MD: Clinical characteristics and prognosis of osteosarcoma in young children: A retrospective series of 15 cases. BMC Cancer. 11:4072011. View Article : Google Scholar :
2	Ritter J and Bielack SS: Osteosarcoma. Ann Oncol. 21 Suppl 7:vii320–vii325. 2010. View Article : Google Scholar
3	Williams SA, Maecker HL, French DM, Liu J, Gregg A, Silverstein LB, Cao TC, Carano RA and Dixit VM: USP1 deubiquitinates ID proteins to preserve a mesenchymal stem cell program in osteosarcoma. Cell. 146:918–930. 2011. View Article : Google Scholar
4	Bacci G, Briccoli A, Rocca M, Ferrari S, Donati D, Longhi A, Bertoni F, Bacchini P, Giacomini S, Forni C, et al: Neoadjuvant chemotherapy for osteosarcoma of the extremities with metastases at presentation: Recent experience at the Rizzoli Institute in 57 patients treated with cisplatin, doxorubicin, and a high dose of methotrexate and ifosfamide. Ann Oncol. 14:1126–1134. 2003. View Article : Google Scholar
5	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
6	Benjamin RS: Osteosarcoma: Better treatment through better trial design. Lancet Oncol. 16:12–13. 2015. View Article : Google Scholar
7	Letson GD and Muro-Cacho CA: Genetic and molecular abnormalities in tumors of the bone and soft tissues. Cancer Control. 8:239–251. 2001. View Article : Google Scholar
8	Haghikia A, Hoch M, Stapel B and Hilfiker-Kleiner D: STAT3 regulation of and by microRNAs in development and disease. JAKSTAT. 1:143–150. 2012.
9	Griffiths-Jones S, Grocock RJ, van Dongen S, Bateman A and Enright AJ: miRBase: microRNA sequences, targets and gene nomenclature. Nucleic Acids Res. 34:(Database Issue). D140–D144. 2006. View Article : Google Scholar
10	Namløs HM, Meza-Zepeda LA, Barøy T, Østensen IH, Kresse SH, Kuijjer ML, Serra M, Bürger H, Cleton-Jansen AM and Myklebost O: Modulation of the osteosarcoma expression phenotype by microRNAs. PLoS One. 7:e480862012. View Article : Google Scholar :
11	Li D, Zhao Y, Liu C, Chen X, Qi Y, Jiang Y, Zou C, Zhang X, Liu S, Wang X, et al: Analysis of MiR-195 and MiR-497 expression, regulation and role in breast cancer. Clin Cancer Res. 17:1722–1730. 2011. View Article : Google Scholar
12	Li Z, Yu X, Shen J and Jiang Y: MicroRNA dysregulation in uveal melanoma: A new player enters the game. Oncotarget. 6:4562–4568. 2015. View Article : Google Scholar :
13	Li Z, Yu X, Wang Y, Shen J, Wu WK, Liang J and Feng F: By downregulating TIAM1 expression, microRNA-329 suppresses gastric cancer invasion and growth. Oncotarget. 6:17559–17569. 2015. View Article : Google Scholar :
14	Li Z, Yu X, Shen J, Law PT, Chan MT and Wu WK: MicroRNA expression and its implications for diagnosis and therapy of gallbladder cancer. Oncotarget. 6:13914–13921. 2015. View Article : Google Scholar :
15	Iorio MV and Croce CM: Causes and consequences of microRNA dysregulation. Cancer J. 18:215–222. 2012. View Article : Google Scholar :
16	Garzon R, Liu S, Fabbri M, Liu Z, Heaphy CE, Callegari E, Schwind S, Pang J, Yu J, Muthusamy N, et al: MicroRNA-29b induces global DNA hypomethylation and tumor suppressor gene reexpression in acute myeloid leukemia by targeting directly DNMT3A and 3B and indirectly DNMT1. Blood. 113:6411–6418. 2009. View Article : Google Scholar :
17	Fenger JM, Roberts RD, Iwenofu OH, Bear MD, Zhang X, Couto JI, Modiano JF, Kisseberth WC and London CA: MiR-9 is overexpressed in spontaneous canine osteosarcoma and promotes a metastatic phenotype including invasion and migration in osteoblasts and osteosarcoma cell lines. BMC Cancer. 16:7842016. View Article : Google Scholar :
18	Ventura A and Jacks T: MicroRNAs and cancer: Short RNAs go a long way. Cell. 136:586–591. 2009. View Article : Google Scholar :
19	Yang T, Thakur A, Chen T, Yang L, Lei G, Liang Y, Zhang S, Ren H and Chen M: MicroRNA-15a induces cell apoptosis and inhibits metastasis by targeting BCL2L2 in non-small cell lung cancer. Tumour Biol. 36:4357–4365. 2015. View Article : Google Scholar
20	Lou X, Qi X, Zhang Y, Long H and Yang J: Decreased expression of microRNA-625 is associated with tumor metastasis and poor prognosis in patients with colorectal cancer. J Surg Oncol. 108:230–235. 2013. View Article : Google Scholar
21	Wang M, Li C, Nie H, Lv X, Qu Y, Yu B, Su L, Li J, Chen X, Ju J, et al: Down-regulated miR-625 suppresses invasion and metastasis of gastric cancer by targeting ILK. FEBS Lett. 586:2382–2388. 2012. View Article : Google Scholar
22	Zhou X, Zhang CZ, Lu SX, Chen GG, Li LZ, Liu LL, Yi C, Fu J, Hu W, Wen JM and Yun JP: miR-625 suppresses tumour migration and invasion by targeting IGF2BP1 in hepatocellular carcinoma. Oncogene. 34:965–977. 2015. View Article : Google Scholar
23	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
24	Zeng Q and Hong W: The emerging role of the hippo pathway in cell contact inhibition, organ size control, and cancer development in mammals. Cancer Cell. 13:188–192. 2008. View Article : Google Scholar
25	Liu H, Li W, Chen C, Pei Y and Long X: MiR-335 acts as a potential tumor suppressor miRNA via downregulating ROCK1 expression in hepatocellular carcinoma. Tumour Biol. 36:6313–6319. 2015. View Article : Google Scholar
26	Tu Y, Liu L, Zhao D, Liu Y, Ma X, Fan Y, Wan L, Huang T, Cheng Z and Shen B: Overexpression of miRNA-497 inhibits tumor angiogenesis by targeting VEGFR2. Sci Rep. 5:138272015. View Article : Google Scholar :
27	Shin JY, Kim YI, Cho SJ, Lee MK, Kook MC, Lee JH, Lee SS, Ashktorab H, Smoot DT, Ryu KW, et al: MicroRNA 135a suppresses lymph node metastasis through down-regulation of ROCK1 in early gastric cancer. PLoS One. 9:e852052014. View Article : Google Scholar :
28	Li C, Li DC, Che SS, Ma K, Wang YJ, Xia LH, Dai XM, Zhang GT, Shen Y, Jiao WJ and Tian KH: The decreased expression of miR-625 predicts poor prognosis of esophageal squamous cell carcinoma. Int J Clin Exp Med. 8:9560–9564. 2015.
29	Wang Z, Qiao Q, Chen M, Li X, Wang Z, Liu C and Xie Z: miR-625 down-regulation promotes proliferation and invasion in esophageal cancer by targeting Sox2. FEBS Lett. 588:915–921. 2014. View Article : Google Scholar
30	Zhou WB, Zhong CN, Luo XP, Zhang YY, Zhang GY, Zhou DX and Liu LP: miR-625 suppresses cell proliferation and migration by targeting HMGA1 in breast cancer. Biochem Biophys Res Commun. 470:838–844. 2016. View Article : Google Scholar
31	Hwang HW and Mendell JT: MicroRNAs in cell proliferation, cell death, and tumorigenesis. Br J Cancer. 96 Suppl:R40–R44. 2007.
32	Orr BA, Bai H, Odia Y, Jain D, Anders RA and Eberhart CG: Yes-associated protein 1 is widely expressed in human brain tumors and promotes glioblastoma growth. J Neuropathol Exp Neurol. 70:568–577. 2011. View Article : Google Scholar :
33	Lee KW, Lee SS, Kim SB, Sohn BH, Lee HS, Jang HJ, Park YY, Kopetz S, Kim SS, Oh SC and Lee JS: Significant association of oncogene YAP1 with poor prognosis and cetuximab resistance in colorectal cancer patients. Clin Cancer Res. 21:357–364. 2015. View Article : Google Scholar
34	Kang W, Tong JH, Chan AW, Lee TL, Lung RW, Leung PP, So KK, Wu K, Fan D, Yu J, et al: Yes-associated protein 1 exhibits oncogenic property in gastric cancer and its nuclear accumulation associates with poor prognosis. Clin Cancer Res. 17:2130–2139. 2011. View Article : Google Scholar
35	Li S, Yu Z, Chen SS, Li F, Lei CY, Chen XX, Bao JM, Luo Y, Lin GZ, Pang SY and Tan WL: The YAP1 oncogene contributes to bladder cancer cell proliferation and migration by regulating the H19 long noncoding RNA. Urol Oncol. 33(427): e1–10. 2015.
36	Zhang YH, Li B, Shen L, Shen Y and Chen XD: The role and clinical significance of YES-associated protein 1 in human osteosarcoma. Int J Immunopathol Pharmacol. 26:157–167. 2013. View Article : Google Scholar
37	Yang Z, Zhang M, Xu K, Liu L, Hou WK, Cai YZ, Xu P and Yao JF: Knockdown of YAP1 inhibits the proliferation of osteosarcoma cells in vitro and in vivo. Oncol Rep. 32:1265–1272. 2014. View Article : Google Scholar