Abstract
Prior studies have noted the importance of microRNAs (miRNAs) in development and progression of osteosarcoma (OS), but the influence of miR-301b is less investigated. This investigation aimed to explore the biological role of miR-301b/SNX10 in OS. GSE28423 and GSE28424 arrays delivered the corresponding miR-301b and sorting nexin 10 (SNX10) expression levels in OS samples. miR-301b and SNX10 expressions were also measured by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting in cells. Cell counting kit (CCK)-8 and transwell analysis were applied to measure cell characteristics. Luciferase reporter assay and Pearson correlation analysis were used to detect the relevance between miR-301b and SNX10. miR-301b was extremely increased in OS tissues compared with normal tissues, while SNX10 was decreased. The proliferation, invasion, and migration capabilities were limited following a low expression level of miR-301b whereas miR-301b overexpression promoted cellular malignant behaviors. miR-301b negatively targeted SNX10. The elevated SNX10 expression highlighted the inhibitory function on cell proliferation, migration, and invasion in OS cells treated by miR-301b inhibitor. Reduction of miR-301b induced the decrease of epithelial-mesenchymal transition (EMT)-related markers including N-cadherin, Vimentin, and matrix metallo-proteinase 9 (MMP)9. These results are added to the complete expanding field of the potential effects of miR-301b in OS cell malignant behaviors and demonstrate its promising role for further use to treat human OS.
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References
Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297. https://doi.org/10.1016/s0092-8674(04)00045-5
Bielack S, Kempf-Bielack B, Von Kalle T, Schwarz R, Wirth T, Kager L et al (2013) Controversies in childhood osteosarcoma. Minerva Pediatr 65:125–148. https://doi.org/10.1016/j.jaapos.2013.02.001
Carina V, Costa V, Sartori M, Bellavia D, De Luca A, Raimondi L et al (2019) Adjuvant biophysical therapies in osteosarcoma. Cancers (basel). https://doi.org/10.3390/cancers11030348
Cervantes-Anaya N, Ponciano-Gomez A, Lopez-Alvarez GS, Gonzalez-Reyes C, Hernandez-Garcia S, Cabanas-Cortes MA et al (2017) Downregulation of sorting nexin 10 is associated with overexpression of miR-30d during liver cancer progression in rats. Tumour Biol. https://doi.org/10.1177/1010428317695932
Chen J, Yan D, Wu W, Zhu J, Ye W, Shu Q (2016) MicroRNA-130a promotes the metastasis and epithelial-mesenchymal transition of osteosarcoma by targeting PTEN. Oncol Rep 35:3285–3292. https://doi.org/10.3892/or.2016.4719
Diepenbruck M, Christofori G (2016) Epithelial-mesenchymal transition (EMT) and metastasis: yes, no, maybe? Curr Opin Cell Biol 43:7–13. https://doi.org/10.1016/j.ceb.2016.06.002
Egawa H, Jingushi K, Hirono T, Ueda Y, Kitae K, Nakata W et al (2016) The miR-130 family promotes cell migration and invasion in bladder cancer through FAK and Akt phosphorylation by regulating PTEN. Sci Rep 6:20574. https://doi.org/10.1038/srep20574
Han K, Zhao T, Chen X, Bian N, Yang T, Ma Q et al (2014) microRNA-194 suppresses osteosarcoma cell proliferation and metastasis in vitro and in vivo by targeting CDH2 and IGF1R. Int J Oncol 45:1437–1449. https://doi.org/10.3892/ijo.2014.2571
Han X, Wang W, He J, Jiang L, Li X (2019) Osteopontin as a biomarker for osteosarcoma therapy and prognosis. Oncol Lett 17:2592–2598. https://doi.org/10.3892/ol.2019.9905
Hao H, Chen L, Huang D, Ge J, Qiu Y, Hao L (2017) Meta-analysis of alkaline phosphatase and prognosis for osteosarcoma. Eur J Cancer Care (engl). https://doi.org/10.1111/ecc.12536
Izadpanah S, Shabani P, Aghebati-Maleki A, Baghbani E, Baghbanzadeh A, Fotouhi A et al (2019) Insights into the roles of miRNAs; miR-193 as one of small molecular silencer in osteosarcoma therapy. Biomed Pharmacother 111:873–881. https://doi.org/10.1016/j.biopha.2018.12.106
Kang HG, Kim HS, Kim KJ, Oh JH, Lee MR, Seol SM et al (2007) RECK expression in osteosarcoma: correlation with matrix metalloproteinases activation and tumor invasiveness. J Orthop Res 25:696–702. https://doi.org/10.1002/jor.20323
Kotiyal S, Bhattacharya S (2016) Events of molecular changes in epithelial-mesenchymal transition. Crit Rev Eukaryot Gene Expr 26:163–171. https://doi.org/10.1615/CritRevEukaryotGeneExpr.2016016307
Lamouille S, Xu J, Derynck R (2014) Molecular mechanisms of epithelial-mesenchymal transition. Nat Rev Mol Cell Biol 15:178–196. https://doi.org/10.1038/nrm3758
Le Y, Zhang S, Ni J, You Y, Luo K, Yu Y et al (2018) Sorting nexin 10 controls mTOR activation through regulating amino-acid metabolism in colorectal cancer. Cell Death Dis 9:666. https://doi.org/10.1038/s41419-018-0719-2
Li Z, Hassan MQ, Volinia S, van Wijnen AJ, Stein JL, Croce CM et al (2008) A microRNA signature for a BMP2-induced osteoblast lineage commitment program. Proc Natl Acad Sci USA 105:13906–13911. https://doi.org/10.1073/pnas.0804438105
Li BL, Lu C, Lu W, Yang TT, Qu J, Hong X et al (2013) miR-130b is an EMT-related microRNA that targets DICER1 for aggression in endometrial cancer. Med Oncol 30:484. https://doi.org/10.1007/s12032-013-0484-0
Ma C, Zhan C, Yuan H, Cui Y, Zhang Z (2016) MicroRNA-603 functions as an oncogene by suppressing BRCC2 protein translation in osteosarcoma. Oncol Rep 35:3257–3264. https://doi.org/10.3892/or.2016.4718
Mittal V (2016) Epithelial mesenchymal transition in aggressive lung cancers. Adv Exp Med Biol 890:37–56. https://doi.org/10.1007/978-3-319-24932-2_3
Ni Z, Shang XF, Wang YF, Sun YJ, Fu DJ (2016) Upregulated microRNA-301a in osteosarcoma promotes tumor progression by targeting CDC14A. Genet Mol Res. https://doi.org/10.4238/gmr.15027807
Ottaviani G, Jaffe N (2009) The epidemiology of osteosarcoma. Cancer Treat Res 152:3–13. https://doi.org/10.1007/978-1-4419-0284-9_1
Qin B, He M, Chen X, Pei D (2006) Sorting nexin 10 induces giant vacuoles in mammalian cells. J Biol Chem 281:36891–36896. https://doi.org/10.1074/jbc.M608884200
Rupaimoole R, Slack FJ (2017) MicroRNA therapeutics: towards a new era for the management of cancer and other diseases. Nat Rev Drug Discov 16:203–222. https://doi.org/10.1038/nrd.2016.246
Sakamoto A, Iwamoto Y (2008) Current status and perspectives regarding the treatment of osteo-sarcoma: chemotherapy. Rev Recent Clin Trials 3:228–231. https://doi.org/10.2174/157488708785700267
Xu T, Xu J, Ye Y, Wang Q, Shu X, Pei D et al (2014) Structure of human SNX10 reveals insights into its role in human autosomal recessive osteopetrosis. Proteins 82:3483–3489. https://doi.org/10.1002/prot.24689
Ye L, Morse LR, Zhang L, Sasaki H, Mills JC, Odgren PR et al (2015) Osteopetrorickets due to Snx10 deficiency in mice results from both failed osteoclast activity and loss of gastric acid-dependent calcium absorption. PLoS Genet 11:e1005057. https://doi.org/10.1371/journal.pgen.1005057
Zhou Z, Wang Z, Wei H, Wu S, Wang X, Xiao J (2016) Promotion of tumour proliferation, migration and invasion by miR-92b in targeting RECK in osteosarcoma. Clin Sci (lond) 130:921–930. https://doi.org/10.1042/cs20150509
Zhu CH, Morse LR, Battaglino RA (2012) SNX10 is required for osteoclast formation and resorption activity. J Cell Biochem 113:1608–1615. https://doi.org/10.1002/jcb.24029
Ziyan W, Shuhua Y, Xiufang W, Xiaoyun L (2011) MicroRNA-21 is involved in osteosarcoma cell invasion and migration. Med Oncol 28:1469–1474. https://doi.org/10.1007/s12032-010-9563-7
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Wang, Y., Sun, N., Zhang, Z. et al. Overexpression Pattern of miR-301b in Osteosarcoma and Its Relevance with Osteosarcoma Cellular Behaviors via Modulating SNX10. Biochem Genet 61, 87–100 (2023). https://doi.org/10.1007/s10528-022-10241-4
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DOI: https://doi.org/10.1007/s10528-022-10241-4