Abstract
Cancer driver genes (CDGs) and the driver mutations disrupt the homeostasis of numerous critical cell activities, thereby playing a critical role in tumor initiation and progression. In this study, integrative bioinformatics analyses were performed based on a series of online databases, aiming to identify driver genes with high frequencies of mutations in head and neck cancers. Higher myeloma overexpressed (MYEOV) genetic variation frequency and expression level were connected to a poorer prognosis in head and neck cancer patients. MYEOV was dramatically upregulated within head and neck tumor samples and cells. Consistently, MYEOV overexpression remarkably enhanced the aggressiveness of head and neck cancer cells by promoting colony formation, cell invasion, and cell migration. Conversely, MYEOV knockdown attenuated cancer cell aggressiveness and inhibited tumor growth and metastasis in the oral orthotopic tumor model. In conclusion, MYEOV is overexpressed in head and neck cancer, with greater mutation frequencies correlating to a poorer prognosis in head and neck cancer patients. MYEOV serves as an oncogene in head and neck cancer through the promotion of tumor cell colony formation, invasion, and migration, as well as promoting tumor growth and metastasis in the oral orthotopic tumor model.
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References
Agrawal N et al (2011) Exome sequencing of head and neck squamous cell carcinoma reveals inactivating mutations in NOTCH1. Science 333(6046):1154–1157
Akhtar J et al (2014) Effectiveness of local injection of lentivirus-delivered stathmin1 and stathmin1 shRNA in human gastric cancer xenograft mouse. J Gastroenterol Hepatol 29(9):1685–1691
Ausoni S et al (2016) Targeting cellular and molecular drivers of head and neck squamous cell carcinoma: current options and emerging perspectives. Cancer Metastasis Rev 35(3):413–426
Bailey MH et al (2018) Comprehensive characterization of cancer driver genes and mutations. Cell 173(2):371-385 e18
Cancer Genome Atlas Network (2015) Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature 517(7536):576–582
Cancer Genome Atlas Research Network (2013) The Cancer Genome Atlas Pan-Cancer analysis project. Nat Genet 45(10):1113–1120
Cao ZQ, Wang Z, Leng P (2019) Aberrant N-cadherin expression in cancer. Biomed Pharmacother 118:109320
Dent P (2013) FADD the bad in head and neck cancer. Cancer Biol Ther 14(9):780–781
Fang L et al (2019) MYEOV functions as an amplified competing endogenous RNA in promoting metastasis by activating TGF-beta pathway in NSCLC. Oncogene 38(6):896–912
Freier K et al (2006) Recurrent coamplification of cytoskeleton-associated genes EMS1 and SHANK2 with CCND1 in oral squamous cell carcinoma. Genes Chromosomes Cancer 45(2):118–125
Gao J et al (2013) Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal 6(269):pl1
Glinsky GV (2006) Integration of HapMap-based SNP pattern analysis and gene expression profiling reveals common SNP profiles for cancer therapy outcome predictor genes. Cell Cycle 5(22):2613–2625
Goldman MJ et al (2020) Visualizing and interpreting cancer genomics data via the Xena platform. Nat Biotechnol 38(6):675–678
Gurubhagavatula S et al (2004) XPD and XRCC1 genetic polymorphisms are prognostic factors in advanced non-small-cell lung cancer patients treated with platinum chemotherapy. J Clin Oncol 22(13):2594–2601
Heist RS et al (2007) MDM2 polymorphism, survival, and histology in early-stage non-small-cell lung cancer. J Clin Oncol 25(16):2243–2247
Hopkins J et al (2008) Genetic polymorphisms and head and neck cancer outcomes: a review. Cancer Epidemiol Biomark Prev 17(3):490–499
Ideta Y et al (2021) Transcriptomic profiling predicts multiple pathways and molecules associated with the metastatic phenotype of oral cancer cells. Cancer Genom Proteom 18(1):17–27
International Cancer Genome Consortium (2010) International network of cancer genome projects. Nature 464(7291):993–998
Izzo JG et al (2007) Cyclin D1 guanine/adenine 870 polymorphism with altered protein expression is associated with genomic instability and aggressive clinical biology of esophageal adenocarcinoma. J Clin Oncol 25(6):698–707
Jamroziak K, Robak T (2004) Pharmacogenomics of MDR1/ABCB1 gene: the influence on risk and clinical outcome of haematological malignancies. Hematology 9(2):91–105
Janssen JW et al (2000) Concurrent activation of a novel putative transforming gene, myeov, and cyclin D1 in a subset of multiple myeloma cell lines with t(11;14)(q13;q32). Blood 95(8):2691–2698
Janssen JW et al (2002a) MYEOV: a candidate gene for DNA amplification events occurring centromeric to CCND1 in breast cancer. Int J Cancer 102(6):608–614
Janssen JW et al (2002b) MYEOV, a gene at 11q13, is coamplified with CCND1, but epigenetically inactivated in a subset of esophageal squamous cell carcinomas. J Hum Genet 47(9):460–464
Li Y, Zhang J, Hong S (2014) ANO1 as a marker of oral squamous cell carcinoma and silencing ANO1 suppresses migration of human SCC-25 cells. Med Oral Patol Oral Cir Bucal 19(4):e313–e319
Liang E et al (2020) MYEOV increases HES1 expression and promotes pancreatic cancer progression by enhancing SOX9 transactivity. Oncogene 39(41):6437–6450
Liu P et al (2009) Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov 8(8):627–644
Liu Z et al (2012) Manganese superoxide dismutase induces migration and invasion of tongue squamous cell carcinoma via H2O2-dependent Snail signaling. Free Radic Biol Med 53(1):44–50
Liu H et al (2018) LncRNA XIST/miR-34a axis modulates the cell proliferation and tumor growth of thyroid cancer through MET-PI3K-AKT signaling. J Exp Clin Cancer Res 37(1):279
Martinez-Balibrea E et al (2007) Combined analysis of genetic polymorphisms in thymidylate synthase, uridine diphosphate glucoronosyltransferase and X-ray cross complementing factor 1 genes as a prognostic factor in advanced colorectal cancer patients treated with 5-fluorouracil plus oxaliplatin or irinotecan. Oncol Rep 17(3):637–645
Moreaux J et al (2010) MYEOV is a prognostic factor in multiple myeloma. Exp Hematol 38(12):1189-1198 e3
Moss AC et al (2006) ETV4 and Myeov knockdown impairs colon cancer cell line proliferation and invasion. Biochem Biophys Res Commun 345(1):216–221
Mwenifumbo JC, Marra MA (2013) Cancer genome-sequencing study design. Nat Rev Genet 14(5):321–332
Pickering CR et al (2013) Integrative genomic characterization of oral squamous cell carcinoma identifies frequent somatic drivers. Cancer Discov 3(7):770–781
Roomi MW et al (2010) In vitro modulation of MMP-2 and MMP-9 in human cervical and ovarian cancer cell lines by cytokines, inducers and inhibitors. Oncol Rep 23(3):605–614
Seiwert TY et al (2015) Integrative and comparative genomic analysis of HPV-positive and HPV-negative head and neck squamous cell carcinomas. Clin Cancer Res 21(3):632–641
Siegel RL et al (2021) Cancer statistics, 2021. CA Cancer J Clin 71(1):7–33
Soares-Lima SC et al (2021) Upper aerodigestive tract squamous cell carcinomas show distinct overall DNA methylation profiles and different molecular mechanisms behind WNT signaling disruption. Cancers 13(12):3014
Sternlicht MD et al (2006) Prognostic value of PAI1 in invasive breast cancer: evidence that tumor-specific factors are more important than genetic variation in regulating PAI1 expression. Cancer Epidemiol Biomark Prev 15(11):2107–2114
Stransky N et al (2011) The mutational landscape of head and neck squamous cell carcinoma. Science 333(6046):1157–1160
Stratton MR (2011) Exploring the genomes of cancer cells: progress and promise. Science 331(6024):1553–1558
Stratton MR, Campbell PJ, Futreal PA (2009) The cancer genome. Nature 458(7239):719–724
Sung H et al (2021) Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 71(3):209–249
Takita J et al (2011) Aberrations of NEGR1 on 1p31 and MYEOV on 11q13 in neuroblastoma. Cancer Sci 102(9):1645–1650
Tamborero D et al (2018) Cancer Genome Interpreter annotates the biological and clinical relevance of tumor alterations. Genome Med 10(1):25
Tang R et al (2020) Overexpression of MYEOV predicting poor prognosis in patients with pancreatic ductal adenocarcinoma. Cell Cycle 19(13):1602–1610
Thier R et al (2002) Cytochrome P450 1B1, a new keystone in gene-environment interactions related to human head and neck cancer? Arch Toxicol 76(5–6):249–256
Toffoli G, Cecchin E (2007) Clinical implications of genetic polymorphisms on stomach cancer drug therapy. Pharmacogenomics J 7(2):76–80
Wong SHM et al (2018) E-cadherin: its dysregulation in carcinogenesis and clinical implications. Crit Rev Oncol Hematol 121:11–22
Wu X et al (2006) Genetic variations in radiation and chemotherapy drug action pathways predict clinical outcomes in esophageal cancer. J Clin Oncol 24(23):3789–3798
Zhang R, Ma A (2021) High expression of MYEOV reflects poor prognosis in non-small cell lung cancer. Gene 770:145337
Zhang X et al (2018) Systematic analysis of genes involved in oral cancer metastasis to lymph nodes. Cell Mol Biol Lett 23:53
Zhou W et al (2004) Excision repair cross-complementation group 1 polymorphism predicts overall survival in advanced non-small cell lung cancer patients treated with platinum-based chemotherapy. Clin Cancer Res 10(15):4939–4943
Zhu L et al (2019) The pathogenic effect of cortactin tyrosine phosphorylation in cutaneous squamous cell carcinoma. In Vivo 33(2):393–400
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This study was supported by Guangzhou Scientific Research Program Project (201904010045).
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DO and YW conception and design the experiments. DO drafted the article. JZ, JL, ZL, MS contributed to cell and animal experiments. XG revised the article critically for important intellectual content. SC contributed to the analysis.
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10528_2023_10484_MOESM3_ESM.tif
Fig. S3 Effects of MYEOV knockdown on oral cancer cell proliferation, invasion, and migration (A) Image of colony formation assay results. (B) Image of Transwell assay results. (B) Image of Wound healing assay results. Scale bar = 100 μm (TIF 9197 KB)
10528_2023_10484_MOESM4_ESM.tif
Fig. S4 Effects of MYEOV overexpression on oral cancer cell proliferation, invasion, and migration (A) Image of colony formation assay results. (B) Image of Transwell assay results. (B) Image of Wound healing assay results. Scale bar = 100 μm (TIF 12179 KB)
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Ou, D., Wu, Y., Zhang, J. et al. MYEOV with High Frequencies of Mutations in Head and Neck Cancers Facilitates Cancer Cell Malignant Behaviors. Biochem Genet 62, 1657–1674 (2024). https://doi.org/10.1007/s10528-023-10484-9
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DOI: https://doi.org/10.1007/s10528-023-10484-9