Abstract
Background
Dysfunction of microRNAs (miRNAs) is a common characteristic during cancer progression. The suppressive function of miR-5582-3p in cancers has been emerged in recent studies, however, the clinical value and novel targets of miR-5582-3p in osteosarcoma (OS) have not been identified.
Objective
Investigate the function and underlying mechanism of miR-5582-3p in OS.
Results
miR-5582-3p expression was significantly reduced in OS tissues and cells. Lower level of miR-5582-3p had closed relationship with the advanced development and poor 5-year overall survival of OS patients. Transfection of miR-5582-3p in OS cells obviously inhibited the cell proliferation, invasion and colony formation. Highly expressed miR-5582-3p also delayed the cell cycle progression and promoted cell apoptosis. Furthermore, FZD4 was validated as a target of miR-5582-3p. miR-5582-3p interacted with the 3′-untranslated regions (3′-UTR) of FZD4 and reduced FZD4 expression in OS cells. Expression of miR-5582-3p was inversely correlated with that of FZD4 in OS tissues. Transfection of FZD4 rescued the suppressed OS cell proliferation, attenuated miR-5582-3p induced cell apoptosis and invasion.
Conclusions
Our findings uncovered the novel anti-cancer potency of miR-5582-3p in OS via repressing FZD4, suggesting the possibility of miR-5582-3p as a therapeutic target of OS.
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References
Abedini Bakhshmand E, Mohammad Soltani B, Fasihi A, Mowla SJ (2018) Hsa-miR-5582–3P regulatory effect on TGFbeta signaling through targeting of TGFbeta-R1, TGFbeta-R2, SMAD3, and SMAD4 transcripts. J Cell Biochem 119:9921–9930. https://doi.org/10.1002/jcb.27314
Benfey PN (2003) Molecular biology: microRNA is here to stay. Nature 425:244–245. https://doi.org/10.1038/425244a
Cai WT et al (2020) MiRNA-206 suppresses the metastasis of osteosarcoma via targeting Notch3. J Biol Regul Homeost Agents 34:775–783. https://doi.org/10.23812/20-72-A-26
Catto JW et al (2011) MicroRNA in prostate, bladder, and kidney cancer: a systematic review. Eur Urol 59:671–681. https://doi.org/10.1016/j.eururo.2011.01.044
Chang L, Shrestha S, LaChaud G, Scott MA, James AW (2015) Review of microRNA in osteosarcoma and chondrosarcoma. Med Oncol 32:613. https://doi.org/10.1007/s12032-015-0613-z
Cupp AS, Matthews J, Huff-Lonergan E, Spurlock DM, McLean D (2009) Cell biology symposium: the role of microRNA in cell function. J Anim Sci 87:E19-20. https://doi.org/10.2527/jas.2008-1552
Feng ZH et al (2021) EIF4A3-induced circular RNA PRKAR1B promotes osteosarcoma progression by miR-361-3p-mediated induction of FZD4 expression. Cell Death Dis 12:1025. https://doi.org/10.1038/s41419-021-04339-7
Forterre A, Komuro H, Aminova S, Harada M (2020) A comprehensive review of cancer MicroRNA therapeutic Delivery strategies. Cancers (basel). https://doi.org/10.3390/cancers12071852
Geller DS, Gorlick R (2010) Osteosarcoma: a review of diagnosis, management, and treatment strategies. Clin Adv Hematol Oncol 8:705–718
Harb J, Lin PJ, Hao J (2019) Recent development of Wnt signaling pathway inhibitors for cancer therapeutics. Curr Oncol Rep 21:12. https://doi.org/10.1007/s11912-019-0763-9
Hosseinahli N, Aghapour M, Duijf PHG, Baradaran B (2018) Treating cancer with microRNA replacement therapy: a literature review. J Cell Physiol 233:5574–5588. https://doi.org/10.1002/jcp.26514
Jafari F et al (2020) Osteosarcoma: a comprehensive review of management and treatment strategies. Ann Diagn Pathol 49:151654. https://doi.org/10.1016/j.anndiagpath.2020.151654
Katoh M (2007) Networking of WNT, FGF, Notch, BMP, and Hedgehog signaling pathways during carcinogenesis. Stem Cell Rev 3:30–38. https://doi.org/10.1007/s12015-007-0006-6
Kim YM, Kahn M (2014) The role of the Wnt signaling pathway in cancer stem cells: prospects for drug development. Res Rep Biochem 4:1–12. https://doi.org/10.2147/RRBC.S53823
Luhur A, Kumar JP (2008) Advances in microRNA biology. Fly (austin) 2:123–124. https://doi.org/10.4161/fly.6330
Mahajan A et al (2017) Gnathic osteosarcoma: clinical, radiologic, and pathologic review of bone beard tumor. J Glob Oncol 3:823–827. https://doi.org/10.1200/JGO.2016.006494
Matsuyama H, Suzuki HI (2019) Systems and synthetic microRNA biology: from biogenesis to disease pathogenesis. Int J Mol Sci. https://doi.org/10.3390/ijms21010132
Mohr AM, Mott JL (2015) Overview of microRNA biology. Semin Liver Dis 35:3–11. https://doi.org/10.1055/s-0034-1397344
Momtazi AA et al (2016) Curcumin as a MicroRNA regulator in cancer: a review. Rev Physiol Biochem Pharmacol 171:1–38. https://doi.org/10.1007/112_2016_3
Nystrom LM, Reimer NB, Reith JD, Scarborough MT, Gibbs CP Jr (2016) The treatment and outcomes of extraskeletal osteosarcoma: institutional experience and review of the literature. Iowa Orthop J 36:98–103
Sumithra B, Saxena U, Das AB (2016) Alternative splicing within the Wnt signaling pathway: role in cancer development. Cell Oncol (dordr) 39:1–13. https://doi.org/10.1007/s13402-015-0266-0
Taciak B, Pruszynska I, Kiraga L, Bialasek M, Krol M (2018) Wnt signaling pathway in development and cancer. J Physiol Pharmacol. https://doi.org/10.26402/jpp.2018.2.07
Taran SJ, Taran R, Malipatil NB (2017) Pediatric osteosarcoma: an updated review. Indian J Med Paediatr Oncol 38:33–43. https://doi.org/10.4103/0971-5851.203513
Thum T, Mayr M (2012) Review focus on the role of microRNA in cardiovascular biology and disease. Cardiovasc Res 93:543–544. https://doi.org/10.1093/cvr/cvs085
Tiwari A, Mukherjee B, Dixit M (2018) MicroRNA key to angiogenesis regulation: MiRNA biology and therapy. Curr Cancer Drug Targets 18:266–277. https://doi.org/10.2174/1568009617666170630142725
Wang JY et al (2020a) Potential regulatory role of lncRNA-miRNA-mRNA axis in osteosarcoma. Biomed Pharmacother 121:109627. https://doi.org/10.1016/j.biopha.2019.109627
Wang F, Zhao QH, Liu JZ, Kong DL (2020b) MiRNA-188-5p alleviates the progression of osteosarcoma via target degrading CCNT2. Eur Rev Med Pharmacol Sci 24:29–35. https://doi.org/10.26355/eurrev_202001_19892
Watanabe Y, Kanai A (2011) Systems biology reveals MicroRNA-mediated gene regulation. Front Genet 2:29. https://doi.org/10.3389/fgene.2011.00029
Wilbert ML, Yeo GW (2011) Genome-wide approaches in the study of microRNA biology. Wiley Interdiscip Rev Syst Biol Med 3:491–512. https://doi.org/10.1002/wsbm.128
Xiao Y, MacRae IJ (2019) Toward a comprehensive view of MicroRNA biology. Mol Cell 75:666–668. https://doi.org/10.1016/j.molcel.2019.08.001
Yang M, Mattes J (2008) Discovery, biology and therapeutic potential of RNA interference, microRNA and antagomirs. Pharmacol Ther 117:94–104. https://doi.org/10.1016/j.pharmthera.2007.08.004
Zhan T, Rindtorff N, Boutros M (2017) Wnt signaling in cancer. Oncogene 36:1461–1473. https://doi.org/10.1038/onc.2016.304
Zheng A et al (2019) Long non-coding RNA LUCAT1/miR-5582-3p/TCF7L2 axis regulates breast cancer stemness via Wnt/beta-catenin pathway. J Exp Clin Cancer Res 38:305. https://doi.org/10.1186/s13046-019-1315-8
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Wanming Qu: Conceptualization, data curation, formal analysis; Hongbin Zhou: Conceptualization, investigation, data duration, writing-review and editing.
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Qu, W., Zhou, H. MicroRNA-5582-3p alleviates the progression of osteosarcoma via targeting FZD4. Mol. Cell. Toxicol. 19, 363–371 (2023). https://doi.org/10.1007/s13273-022-00267-5
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DOI: https://doi.org/10.1007/s13273-022-00267-5