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Down-regulated expression of miR-582 predicts poor prognosis and facilitates melanoma progression by targeting FOXC1

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Abstract

Melanoma is one of the most common malignant tumors that originate from nerve sheath melanocytes and are produced in the skin and other organs. This paper mainly studied the role of miR-582 in melanoma. The expression of miR-582 in melanoma cell lines and tissues was evaluated by real-time quantitative PCR. Kaplan–Meier curve and Cox proportional hazards model analysis were used to investigate the prognostic value of miR-582 in melanoma. Cell proliferation, invasion, and migration were analyzed using CCK-8 and transwell assays. The results showed that miR-582 was significantly decreased in melanoma cells and tissues. Downregulation of miR-582 was associated with ulceration, lymph node metastasis, TNM stage, and poor overall survival. The functional results showed that low expression of miR-582 can promote cell proliferation, migration, and invasion. FOXC1 was a direct target of miR-582. Overall, the expression of miR-582 is downregulated in melanoma tissues and cell lines. Low expression of miR-582 is associated with prognosis and progression of melanoma by targeting FOXC1. miR-582 may be a prognostic biomarker and a new therapeutic strategy for melanoma.

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Data availability

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

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References

  1. Bender C, Hassel JC, Enk A (2016) Immunotherapy of melanoma. Oncol Res Treat 39(6):369–376. https://doi.org/10.1159/000446716

    Article  CAS  PubMed  Google Scholar 

  2. Lugović-Mihić L, Ćesić D, Vuković P, Novak Bilić G, Šitum M, Špoljar S (2019) Melanoma development: current knowledge on melanoma pathogenesis. Acta Dermatovenerol Croat ADC 27(3):163–168

    PubMed  Google Scholar 

  3. Slominski A, Wortsman J, Carlson AJ, Matsuoka LY, Balch CM, Mihm MC (2001) Malignant melanoma. Arch Pathol Lab Med 125(10):1295–1306. https://doi.org/10.1043/0003-9985(2001)125%3c1295:mm%3e2.0.co;2

    Article  CAS  PubMed  Google Scholar 

  4. Duan H, Jiang K, Wei D, Zhang L, Cheng D, Lv M, Xu Y, He A (2018) Identification of epigenetically altered genes and potential gene targets in melanoma using bioinformatic methods. Onco Targets Ther 11:9–15. https://doi.org/10.2147/ott.s146663

    Article  CAS  PubMed  Google Scholar 

  5. Shen C, Hua H, Gu L, Cao S, Cai H, Yao X, Chen X (2019) miR-124 functions as a melanoma tumor suppressor by targeting RACK1. Onco Targets Ther 12:9975–9986. https://doi.org/10.2147/ott.s225120

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Grimaldi AM, Cassidy PB, Leachmann S, Ascierto PA (2014) Novel approaches in melanoma prevention and therapy. Cancer Treat Res 159:443–455. https://doi.org/10.1007/978-3-642-38007-5_25

    Article  CAS  PubMed  Google Scholar 

  7. Tromme I, Sacré L, Hammouch F, Richez P, Degryse JM, Speybroeck N (2018) Melanoma diagnosis: predictive value of macroscopic changes observed by the patient. Melanoma Res 28(6):611–617. https://doi.org/10.1097/cmr.0000000000000496

    Article  PubMed  Google Scholar 

  8. Ma FC, He RQ, Lin P, Zhong JC, Ma J, Yang H, Hu XH, Chen G (2019) Profiling of prognostic alternative splicing in melanoma. Oncol Lett 18(2):1081–1088. https://doi.org/10.3892/ol.2019.10453

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Zhang XY, Zhang PY (2020) Genetics and epigenetics of melanoma. Oncol Lett 20(5):184. https://doi.org/10.3892/ol.2020.12045

    Article  PubMed  PubMed Central  Google Scholar 

  10. Zhang C, Li H, Wang J, Zhang J, Hou X (2019) MicroRNA-338-3p suppresses cell proliferation, migration and invasion in human malignant melanoma by targeting MACC1. Exp Ther Med 18(2):997–1004. https://doi.org/10.3892/etm.2019.7644

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Huang D, Wang F, Wu W, Lian C, Liu E (2019) MicroRNA-429 inhibits cancer cell proliferation and migration by targeting the AKT1 in melanoma. Cancer Biomark 26(1):63–68. https://doi.org/10.3233/cbm-190289

    Article  CAS  PubMed  Google Scholar 

  12. Sand M, Sand D, Altmeyer P, Bechara FG (2012) MicroRNA in non-melanoma skin cancer. Cancer Biomark 11(6):253–257. https://doi.org/10.3233/cbm-2012-0274

    Article  CAS  PubMed  Google Scholar 

  13. Lee RC, Feinbaum RL, Ambros V (1994) The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75(5):843–854

    Article  Google Scholar 

  14. Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S, Noch E, Aldler H, Rattan S, Keating M, Rai K, Rassenti L, Kipps T, Negrini M, Bullrich F, Croce CM (2002) Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci USA 99(24):15524–15529. https://doi.org/10.1073/pnas.242606799

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Ray A, Kunhiraman H, Perera RJ (2020) The paradoxical behavior of microRNA-211 in melanomas and other human cancers. Front Oncol 10:628367. https://doi.org/10.3389/fonc.2020.628367

    Article  PubMed  Google Scholar 

  16. Caramuta S, Egyházi S, Rodolfo M, Witten D, Hansson J, Larsson C, Lui WO (2010) MicroRNA expression profiles associated with mutational status and survival in malignant melanoma. J Investig Dermatol 130(8):2062–2070. https://doi.org/10.1038/jid.2010.63

    Article  CAS  PubMed  Google Scholar 

  17. Peng J, Liu H, Liu C (2017) MiR-155 promotes uveal melanoma cell proliferation and invasion by regulating NDFIP1 expression. Technol Cancer Res Treat 16(6):1160–1167. https://doi.org/10.1177/1533034617737923

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Arnold J, Engelmann JC, Schneider N, Bosserhoff AK, Kuphal S (2020) miR-488-5p and its role in melanoma. Exp Mol Pathol 112:104348. https://doi.org/10.1016/j.yexmp.2019.104348

    Article  CAS  PubMed  Google Scholar 

  19. Lv N, Hao S, Luo C, Abukiwan A, Hao Y, Gai F, Huang W, Huang L, Xiao X, Eichmüller SB, He D (2018) miR-137 inhibits melanoma cell proliferation through downregulation of GLO1. Sci China Life Sci 61(5):541–549. https://doi.org/10.1007/s11427-017-9138-9

    Article  CAS  PubMed  Google Scholar 

  20. Li F, Li X, Qiao L, Liu W, Xu C, Wang X (2019) MALAT1 regulates miR-34a expression in melanoma cells. Cell Death Dis 10(6):389. https://doi.org/10.1038/s41419-019-1620-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Luo M, Wu L, Zhang K, Wang H, Zhang T, Gutierrez L, O’Connell D, Zhang P, Li Y, Gao T, Ren W, Yang Y (2018) miR-137 regulates ferroptosis by targeting glutamine transporter SLC1A5 in melanoma. Cell Death Differ 25(8):1457–1472. https://doi.org/10.1038/s41418-017-0053-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Weber CE, Luo C, Hotz-Wagenblatt A, Gardyan A, Kordaß T, Holland-Letz T, Osen W, Eichmüller SB (2016) miR-339-3p is a tumor suppressor in melanoma. Can Res 76(12):3562–3571. https://doi.org/10.1158/0008-5472.can-15-2932

    Article  CAS  Google Scholar 

  23. Xie M, Yu T, Jing X, Ma L, Fan Y, Yang F, Ma P, Jiang H, Wu X, Shu Y (2020) Exosomal circSHKBP1 promotes gastric cancer progression via regulating the miR-582-3p/HUR/VEGF axis and suppressing HSP90 degradation. Mol Cancer 19(1):112. https://doi.org/10.1186/s12943-020-01208-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Huang S, Zou C, Tang Y, Wa Q, Peng X, Chen X, Yang C, Ren D, Huang Y, Liao Z, Huang S, Zou X, Pan J (2019) miR-582-3p and miR-582-5p suppress prostate cancer metastasis to bone by repressing TGF-β signaling. Mol Ther Nucleic acids 16:91–104. https://doi.org/10.1016/j.omtn.2019.01.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Xu T, Tian Y, Guan Y, Su Y, Luo W, Yang G, Zhang Y (2020) MiR-582-5p inhibits bladder cancer-genesis by suppressing TTK expression. Mol Cancer 12:11933–11944. https://doi.org/10.2147/cmar.s274835

    Article  CAS  Google Scholar 

  26. Wang LL, Zhang M (2018) miR-582-5p is a potential prognostic marker in human non-small cell lung cancer and functions as a tumor suppressor by targeting MAP3K2. Eur Rev Med Pharmacol Sci 22(22):7760–7767. https://doi.org/10.26355/eurrev_201811_16397

    Article  PubMed  Google Scholar 

  27. Zhang Y, Huang W, Ran Y, Xiong Y, Zhong Z, Fan X, Wang Z, Ye Q (2015) miR-582-5p inhibits proliferation of hepatocellular carcinoma by targeting CDK1 and AKT3. Tumour Biol 36(11):8309–8316. https://doi.org/10.1007/s13277-015-3582-0

    Article  CAS  PubMed  Google Scholar 

  28. Tian Y, Guan Y, Su Y, Luo W, Yang G, Zhang Y (2020) MiR-582-5p inhibits bladder cancer-genesis by suppressing TTK expression. Cancer Manag Res 12:11933–11944. https://doi.org/10.2147/cmar.s274835

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Ye CY, Zheng CP, Zhou WJ, Weng SS (2020) MiR-582-5p inhibits the growth and invasion of osteosarcoma cell by targeting NOVA1. Eur Rev Med Pharmacol Sci 24(21):11026–11031. https://doi.org/10.26355/eurrev_202011_23587

    Article  PubMed  Google Scholar 

  30. Li L, Ma L (2018) Upregulation of miR-582-5p regulates cell proliferation and apoptosis by targeting AKT3 in human endometrial carcinoma. Saudi J Biol Sci 25(5):965–970. https://doi.org/10.1016/j.sjbs.2018.03.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Wang WW, Chen B, Lei CB, Liu GX, Wang YG, Yi C, Wang YY, Zhang SY (2017) miR-582-5p inhibits invasion and migration of salivary adenoid cystic carcinoma cells by targeting FOXC1. Jpn J Clin Oncol 47(8):690–698. https://doi.org/10.1093/jjco/hyx073

    Article  PubMed  Google Scholar 

  32. Cao S, Wang Z, Gao X, He W, Cai Y, Chen H, Xu R (2018) FOXC1 induces cancer stem cell-like properties through upregulation of beta-catenin in NSCLC. J Exp Clin Cancer Res CR 37(1):220. https://doi.org/10.1186/s13046-018-0894-0

    Article  CAS  PubMed  Google Scholar 

  33. Subramani R, Camacho FA, Levin CI, Flores K, Clift A, Galvez A, Terres M, Rivera S, Kolli SN, Dodderer J, Miranda M, Rodriguez A, Pedroza DA, Chatterjee A, Lakshmanaswamy R (2018) FOXC1 plays a crucial role in the growth of pancreatic cancer. Oncogenesis 7(7):52. https://doi.org/10.1038/s41389-018-0061-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Liu Z, Xu S, Chu H, Lu Y, Yuan P, Zeng X (2018) Silencing FOXC1 inhibits growth and migration of human oral squamous cell carcinoma cells. Exp Ther Med 16(4):3369–3376. https://doi.org/10.3892/etm.2018.6627

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Wang J, Li L, Liu S, Zhao Y, Wang L, Du G (2016) FOXC1 promotes melanoma by activating MST1R/PI3K/AKT. Oncotarget 7(51):84375–84387. https://doi.org/10.18632/oncotarget.11224

    Article  PubMed  PubMed Central  Google Scholar 

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Correspondence to Dapeng Zhang.

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Chen, F., Zhang, D. Down-regulated expression of miR-582 predicts poor prognosis and facilitates melanoma progression by targeting FOXC1. Arch Dermatol Res 314, 759–766 (2022). https://doi.org/10.1007/s00403-021-02285-0

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