Overexpression of MYBL2 predicts poor prognosis and promotes oncogenesis in endometrial carcinoma

Submitted: 7 February 2021
Accepted: 20 March 2021
Published: 30 March 2021
Abstract Views: 935
PDF: 566
Supplementary: 100
HTML: 9
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Authors

Endometrial cancer (EC) is the most common gynecologic malignancy and still remains clinically challenging. We aimed to explore the potential biomarkers of EC and provide a theoretical basis for early screening and targeted therapy. The available transcriptome data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were analyzed to identify differentially expressed genes. Immunohistochemistry was performed to detect gene expression. We analyzed the associations of MYBL2 with clinicopathological features and survival time and the biological effect of MYBL2 on the proliferation of EC cells. The effect of MYBL2 silencing on the transcriptome of EC cell model was analyzed by RNA-Seq. MYBL2 was significantly upregulated with obvious copy number alteration (CNA) in EC. Copy number amplification significantly increased MYBL2 mRNA expression, which led to a poor prognosis and severe pathological types of EC. Additionally, MYBL2 silencing significantly inhibited proliferation and induced apoptosis and G1-phase cell cycle arrest in EC cell lines. Our results indicate that MYBL2 is closely related to the cell cycle and apoptosis pathways in EC. The findings in this study provide evidence that MYBL2 can serve as a new candidate prognostic marker and a target for future therapeutic intervention in EC.

Dimensions

Altmetric

PlumX Metrics

Downloads

Download data is not yet available.

Citations

Felix AS, Yang HP, Bell DW, Sherman ME. Epidemiology of endometrial carcinoma: Etiologic importance of hormonal and metabolic influences. Adv Exp Med Biol 2017;943:3-26. DOI: https://doi.org/10.1007/978-3-319-43139-0_1
Hamilton CA, Cheung MK, Osann K, Chen L, Teng NN, Longacre TA, et al. Uterine papillary serous and clear cell carcinomas predict for poorer survival compared to grade 3 endometrioid corpus cancers. Br J Cancer 2016;94:642-6. DOI: https://doi.org/10.1038/sj.bjc.6603012
Bestvina CM, Fleming GF. Chemotherapy for endometrial cancer in adjuvant and advanced disease settings. Oncologist 2016;21:1250-9. DOI: https://doi.org/10.1634/theoncologist.2016-0062
Viet CT, Schmidt BL. Understanding oral cancer in the genome era. Head Neck 2010;32:1246-68. DOI: https://doi.org/10.1002/hed.21358
Sischo L, Broder HL. Oral health-related quality of life: what, why, how, and future implications. J Dent Res 2011;90:1264-70. DOI: https://doi.org/10.1177/0022034511399918
Pinkel D, Segraves R, Sudar D, Clark S, Poole I, Kowbel D, et al. High resolution analysis of DNA copy number variation using comparative genomic hybridization to microarrays. Nat Genet 1998;20:207-11. DOI: https://doi.org/10.1038/2524
Hanahan D, Weinberg RA. Hallmarks of cancer: The next generation. Cell 2011;144:646-74. DOI: https://doi.org/10.1016/j.cell.2011.02.013
Kumaran M, Cass CE, Graham K, Mackey JR, Hubaux R, Lam W, et al. Germline copy number variations are associated with breast cancer risk and prognosis. Sci Rep 2017;7:14621. DOI: https://doi.org/10.1038/s41598-017-14799-7
Moir-Meyer GL, Pearson JF, Lose F, Australian National Endometrial Cancer Study Group, Scott RJ, McEvoy M, et al. Rare germline copy number deletions of likely functional importance are implicated in endometrial cancer predisposition. Hum Genet 2015; 134:269-78. DOI: https://doi.org/10.1007/s00439-014-1507-4
Karageorgi S, Prescott J, Wong JYY, Lee IM, Buring JE, De Vivo I. GSTM1 and GSTT1 copy number variation in population-based studies of endometrial cancer risk. Cancer Epidemiol Biomarkers Prev 2011;20:1447-52. DOI: https://doi.org/10.1158/1055-9965.EPI-11-0190
McAlpine J, Leon-Castillo A, Bosse T. The rise of a novel classification system for endometrial carcinoma; integration of molecular subclasses. J Pathol 2018;244:538-549. DOI: https://doi.org/10.1002/path.5034
Diskin SJ, Eck T, Greshock J, Mosse YP, Naylor T, Stoeckert CJ, et al. STAC: A method for testing the significance of DNA copy number aberrations across multiple array-CGH experiments. Genome Res 2006;16:1149-58. DOI: https://doi.org/10.1101/gr.5076506
Pappa KI, Polyzos A, Jacob-Hirsch J, Amariglio N, Vlachos GD, Loutradis D, et al. Profiling of discrete gynecological cancers reveals novel transcriptional modules and common features shared by other cancer types and embryonic stem cells. PLoS One 2015;10:e0142229. DOI: https://doi.org/10.1371/journal.pone.0142229
Day RS, McDade KK, Chandran UR, Lisovich A, Conrads TP, Hood BL, et al. Identifier mapping performance for integrating transcriptomics and proteomics experimental results. BMC Bioinformatics 2011;12:213. DOI: https://doi.org/10.1186/1471-2105-12-213
Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W, et al. Limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res 2015;43:e47. DOI: https://doi.org/10.1093/nar/gkv007
Sandberg ML, Sutton SE, Pletcher MT, Wiltshire T, Tarantino LM, Hogenesch JB, et al. c-Myb and p300 regulate hematopoietic stem cell proliferation and differentiation. Dev Cell 2015;8:53-66.
Malaterre J, Mantamadiotis T, Dworkin S, Lightowler S, Yang Q, Ransome MI, et al. c-Myb is required for neural progenitor cell proliferation and maintenance of the neural stem cell niche in adult brain. Stem Cells 2008;26:173-81. DOI: https://doi.org/10.1634/stemcells.2007-0293
Malaterre J, Carpinelli M, Ernst M, Alexander W, Cooke M, Sutton S, et al. c-Myb is required for progenitor cell homeostasis in colonic crypts. Proc Natl Acad Sci USA 2007;104:3829-34. DOI: https://doi.org/10.1073/pnas.0610055104
Mettus RV, Litvin J, Wali A, Toscani A, Latham K, Hatton K, et al. Murine A-myb: Evidence for differential splicing and tissue-specific expression. Oncogene 1994;9:3077-86.
Tarasov K V., Tarasova YS, Tam WL, Riordon DR, Elliott ST, Kania G, et al. B-MYB is essential for normal cell cycle progression and chromosomal stability of embryonic stem cell. PLoS One 2008;3:e2478. DOI: https://doi.org/10.1371/journal.pone.0002478
Ren F, Wang L, Shen X, Xiao X, Liu Z, Wei P, et al. MYBL2 is an independent prognostic marker that has tumor-promoting functions in colorectal cancer. Am J Cancer Res 2015;5:1542-52.
Guan Z, Cheng W, Huang D, Wei A. High MYBL2 expression and transcription regulatory activity is associated with poor overall survival in patients with hepatocellular carcinoma. Curr Res Transl Med 2018;66:27-32. DOI: https://doi.org/10.1016/j.retram.2017.11.002
Tanner MM, Grenman S, Koul A, Johannsson O, Meltzer P, Pejovic T, et al. Frequent amplification of chromosomal region 20q12-q13 in ovarian cancer. Clin Cancer Res 2000;6:1833-9.
Chin K, DeVries S, Fridlyand J, Spellman PT, Roydasgupta R, Kuo WL, et al. Genomic and transcriptional aberrations linked to breast cancer pathophysiologies. Cancer Cell 2006;10:529-41. DOI: https://doi.org/10.1016/j.ccr.2006.10.009
Liang H Bin, Cao Y, Ma Q, Shu YJ, Wang Z, Zhang F, et al. MYBL2 is a potential prognostic marker that promotes cell proliferation in gallbladder cancer. Cell Physiol Biochem 2017;41:2117-31. DOI: https://doi.org/10.1159/000475454
Thomas C, Robinson C, Dessauvagie B, Wood B, Sterrett G, Harvey J, et al. Expression of proliferation genes in formalin-fixed paraffin-embedded (FFPE) tissue from breast carcinomas. Feasibility and relevance for a routine histopathology laboratory. J Clin Pathol 2017;70:25-32. DOI: https://doi.org/10.1136/jclinpath-2016-203786
Musa J, Aynaud MM, Mirabeau O, Delattre O, Grünewald TG. MYBL2 (B-Myb): a central regulator of cell proliferation, cell survival and differentiation involved in tumorigenesis. Cell Death Dis 2017;8:e2895. DOI: https://doi.org/10.1038/cddis.2017.244
Tanaka Y, Patestos NP, Maekawa T, Ishii S. B-myb is required for inner cell mass formation at an early stage of development. J Biol Chem 1999;274:28067-70. DOI: https://doi.org/10.1074/jbc.274.40.28067

How to Cite

Le, L., Luo, J., Wu, H., Chen, L., Tang, X., & Fu, F. (2021). Overexpression of <em>MYBL2</em> predicts poor prognosis and promotes oncogenesis in endometrial carcinoma. European Journal of Histochemistry, 65(2). https://doi.org/10.4081/ejh.2021.3226