miR-19a-3p Functions as an Oncogene by Regulating FBXO32 Expression in Multiple Myeloma
miR-19a-3p Functions as an Oncogene by Regulating FBXO32 Expression in Multiple Myeloma
Background: Multiple myeloma remains a virtually incurable hematologic malignancy, which is featured with the aberrant growth of malignant plasma cells.Aims: To elucidate the functions of miR-19a-3p in multiple myeloma.Study Design: Cell study.Methods: Cell counting kit-8 assay was performed to detect cell viability, and flow cytometry was conducted to detect cell apoptosis. Bioinformatics analysis predicted miR-19a-3p-associated biological function, pathway, core regulatory network, and target genes. Luciferase reporter assay verified the target sequence of miR-19a-3p regulating FBXO32.Results: miR-19a-3p is upregulated in multiple myeloma cells (p
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- 1. Kyle RA, Rajkumar SV. Multiple Myeloma. Blood 2008;111:2962-72. [Crossref]
- 2. Vicente-Dueñas C, Romero-Camarero I, García-Criado FJ, Cobaleda C, Sánchez-García I. The Cellular Architecture of Multiple Myeloma. Cell Cycle 2012;11:3715-7. [Crossref]
- 3. Yang Y, Shi J, Tolomelli G, Xu H, Xia J, Wang H, et al. RARα2 Expression Confers Myeloma Stem Cell Features. Blood 2013;122:1437-47. [Crossref]
- 4. Zhou W, Yang Y, Gu Z, Wang H, Xia J, Wu X, et al. ALDH1 Activity Identifies Tumor-Initiating Cells and Links to Chromosomal Instability Signatures in Multiple Myeloma. Leukemia. 2014;28:1155-8. [Crossref]
- 5. Zhang X, Chen Y, Zhao P, Zang L, Zhang Z, Wang X. MicroRNA-19a Functions as An Oncogene by Regulating PTEN/AKT/pAKT Pathway in Myeloma. Leuk Lymphoma. 2016;58:932-40. [Crossref]
- 6. Wang JH, Zhou WW, Cheng ST, Liu BX, Liu FR, Song JQ. Downregulation of Sprouty homolog 2 by microRNA-21 Inhibits Proliferation, Metastasis and Invasion, However Promotes the Apoptosis of Multiple Myeloma Cells. Mol Med Rep 2015;12:1810-6. [Crossref]
- 7. Lv H, Wu X, Ma G, Sun L, Meng J, Song X, et al. An Integrated Bioinformatical Analysis of miR‑19a Target Genes in Multiple Myeloma. Exp Ther Med 2017;12:4711-20. [Crossref]
- 8. Rushworth SA, Murray MY, Barrera LN, Heasman S-A, Zaitseva L, MacEwan DJ. Understanding the Role of miRNA in Regulating NF-κB in Blood Cancer. Am J Cancer Res 2012;2:65-74.
- 9. Shi Y, Jin Y. MicroRNA in cell differentiation and development. Sci China C Life Sci 2009;52:205-11. [Crossref]
- 10. Krol J, Loedige I, Filipowicz W. The Widespread Regulation of microRNA Biogenesis, Function and Decay. Nat Rev Genet 2010;11:597-610. [Crossref]
- 11. Hao M, Zang M, Wendlandt E, Xu Y, An G, Gong D, et al. Low Serum miR-19a Expression as a Novel Poor Prognostic Indicator in Multiple Myeloma. Int J Cancer 2015;136:1835-44. [Crossref]
- 12. Gomes MD, Lecker SH, Jagoe RT, Navon A, Goldberg AL. Atrogin-1, a Muscle-Specific F-Box Protein Highly Expressed During Muscle Atrophy. Proc Natl Acad Sci U S A 2001;98:14440-5. [Crossref]
- 13. Zhou H, Liu Y, Zhu R, Ding F, Wan Y, Li Y, et al. FBXO32 Suppresses Breast Cancer Tumorigenesis Through Targeting KLF4 to Proteasomal Degradation. Oncogene 2017;36:3312-21. [Crossref]
- 14. Chou JL, Su HY, Chen LY, Liao YP, Hartman-Frey C, Lai YH, et al. Promoter Hypermethylation of FBXO32, A Novel TGF-beta/SMAD4 Target Gene and Tumor Suppressor, Is Associated with Poor Prognosis in Human Ovarian Cancer. Lab Invest 2010;90:414-25. [Crossref]
- 15. Guo W, Zhang M, Guo Y, Shen S, Guo X, Dong Z. FBXO32, A New TGF-beta/Smad Signaling Pathway Target Gene, Is Epigenetically Inactivated in Gastric Cardia Adenocarcinoma. Neoplasma 2015;62:646-57. [Crossref]
- 16. Wang C, Li X, Zhang J, Ge Z, Chen H, Hu J. EZH2 Contributes to 5-FU Resistance in Gastric Cancer by Epigenetically Suppressing FBXO32 Expression. Onco Targets Ther 2018;11:7853-64. [Crossref]
- 17. Guo W, Zhang M, Shen S, Guo Y, Kuang G, Yang Z, et al. Aberrant Methylation and Decreased Expression of the TGF-β/Smad Target Gene FBXO32 in Esophageal Squamous Cell Carcinoma. Cancer 2014;120:2412-23. [Crossref]
- 18. Stitt TN, Drujan D, Clarke BA, Panaro F, Timofeyva Y, Kline WO, et al. The IGF-1/PI3K/Akt Pathway Prevents Expression of Muscle Atrophy-Induced Ubiquitin Ligases by Inhibiting FOXO Transcription Factors. Mol Cell 20047;14:395-403. [Crossref]
- 19. Baker S, Ali I, Silins I, Pyysalo S, Guo Y, Högberg J, et al. Cancer Hallmarks Analytics Tool (CHAT): A Text Mining Approach to Organize and Evaluate Scientific Literature on Cancer. Bioinformatics 2017;33:3973-81. [Crossref]
- 20. Agarwal V, Bell GW, Nam JW, Bartel DP. Predicting Effective MicroRNA Target Sites in Mammalian mRNAs. Elife 2015;4:e05005. [Crossref]
- 21. Liu W, Wang X. Prediction of Functional Microrna Targets by Integrative Modeling of MicroRNA Binding and Target Expression Data. Genome Biol 2019;20:18. [Crossref]
- 22. Paraskevopoulou MD, Georgakilas G, Kostoulas N, Vlachos IS, Vergoulis T, Reczko M, et al. DIANA-microT Web Server v5.0: Service Integration into miRNA Functional Analysis Workflows. Nucleic Acids Res 2013;41:W169-73. [Crossref]
- 23. Kuleshov MV, Jones MR, Rouillard AD, Fernandez NF, Duan Q, Wang Z, et al. Enrichr: A Comprehensive Gene Set Enrichment Analysis Web Server 2016 Update. Nucleic Acids Res 2016;44:W90-7. [Crossref]
- 24. Szklarczyk D, Gable AL, Lyon D, Junge A, Wyder S, Huerta-Cepas J, et al. STRING v11: Protein-Protein Association Networks with Increased Coverage, Supporting Functional Discovery in Genome-Wide Experimental Datasets. Nucleic Acids Res 2019;47:D607-D13. [Crossref]
- 25. Harousseau JL, Moreau P. Autologous Hematopoietic Stem-Cell Transplantation for Multiple Myeloma. N Engl J Med 2009;360:2645-54. [Crossref]
- 26. Zhong X, Coukos G, Zhang L. miRNAs in Human Cancer. Methods Mol Biol 2012;822:295-306. [Crossref]
- 27. Jiang XM, Yu XN, Liu TT, Zhu HR, Shi X, Bilegsaikhan E, et al. MicroRNA-19a-3p Promotes Tumor Metastasis and Chemoresistance through the PTEN/Akt Pathway in Hepatocellular Carcinoma. Biomed Pharmacother 2018;105:1147-54. [Crossref]
- 28. Yang J, Zhang Z, Chen C, Liu Y, Si Q, Chuang TH, et al. MicroRNA-19a-3p Inhibits Breast Cancer Progression and Metastasis by Inducing Macrophage Polarization Through Downregulated Expression of Fra-1 Proto-Oncogene. Oncogene 2014;33:3014-23. [Crossref]
- 29. Mei Z, Zhang D, Hu B, Wang J, Shen X, Xiao W. FBXO32 Targets c-Myc for Proteasomal Degradation and Inhibits c-Myc Activity. J Biol Chem 2015;290:16202-14. [Crossref]