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

  • Lulu Le Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China.
  • Ji Luo Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China.
  • Haifang Wu Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China.
  • Ling Chen Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China.
  • Xiaoli Tang College of Basic Medical Science, Nanchang University, Nanchang, Jiangxi Province, China.
  • Fen Fu | fu_fen@163.com Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China. https://orcid.org/0000-0002-7823-1816


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.



PlumX Metrics


Download data is not yet available.


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

Endometrial carcinoma, MYBL2, copy number, proliferation, prognosis
  • Abstract views: 228

  • PDF: 114
  • Supplementary: 9
  • HTML: 0
How to Cite
Le, L., Luo, J., Wu, H., Chen, L., Tang, X., & Fu, F. (2021). Overexpression of <em>MYBL2</em&gt; predicts poor prognosis and promotes oncogenesis in endometrial carcinoma. European Journal of Histochemistry, 65(2). https://doi.org/10.4081/ejh.2021.3226