- Volume 15 Issue 23
DOI QR Code
Comprehensive Expression Analysis Suggests Functional Overlapping of Human FOX Transcription Factors in Cancer
- Zhang, Ya-Li (Nantong University) ;
- Sun, Feng-Ting (Nantong University) ;
- Zhang, Ze (Nantong University) ;
- Chen, Xiao-Xu (Nantong University) ;
- Liu, Ai-Xiang (Nantong University) ;
- Pan, Jing-Jing (Nantong University) ;
- Peng, Fei (Nantong University) ;
- Zhou, Shuai (Nantong University) ;
- Sun, Li-Jun (Nantong University)
- Published : 2015.01.06
Forkhead-box (FOX) transcription factors comprise a large gene family that contains more than 50 members in man. Extensive studies have revealed that they not only have functions in control of growth and development, but also play important roles in different diseases, especially in cancer. However, biological functions for most of the members in the FOX family remain unknown. In the present study, the expression of 39 FOX genes in 48 kinds of cancer was mined from the Gene Expression Atlas database of European Bioinformatics Institute. The analysis results showed that some FOX genes demonstrate overlapping expression in various cancers, which suggests particular biological functions. The pleiotropic features of the FOX genes make them excellent candidates in efforts aimed to give medical treatment for cancers at the genetic level. The results also indicated that different FOX genes may have the synergy or antagonistics effects in the same cancers. The study provides clues for further functional analysis of FOX genes, especially for the pleiotropic biological functions and crosstalk of FOX genes in human cancers.
FOX transcription factors;overlapping expression;cancer diseases;gene expression atlas
Supported by : National Natural Science Foundation of China, Natural Science Foundation of Jiangsu Province
- Grasso CS, Wu YM, Robinson DR, et al (2012). The mutational landscape of lethal castration-resistant prostate cancer. Nature, 487, 239-43. https://doi.org/10.1038/nature11125
- Green MR, Aya-Bonilla C, Gandhi MK, et al (2011). Integrative genomic profiling reveals conserved genetic mechanisms for tumorigenesis in common entities of non-Hodgkin's lymphoma. Genes Chromosomes Cancer, 50, 313-26. https://doi.org/10.1002/gcc.20856
- Hannenhalli S, Kaestner KH (2009). The evolution of FOX genes and their role in development and disease. Nat Rev Genet, 10, 233-40.
- Hu X, Stern HM, Ge L, et al (2009). Genetic alterations and oncogenic pathways associated with breast cancer subtypes. Mol Cancer Res, 7, 511-22. https://doi.org/10.1158/1541-7786.MCR-08-0107
- Kaestner KH, Knochel W, Martinez DE (2000). Unified nomenclature for the winged helix/forkhead transcription factors. Genes Dev, 14, 142-6.
- Katoh M, Igarashi M, Fukuda H, et al (2013). Cancer genetics and genomics of human FOX family genes. Cancer Lett, 328, 198-206. https://doi.org/10.1016/j.canlet.2012.09.017
- Bell R, Brice G, Child AH, et al (2001). Analysis of lymphoedemadistichiasis families for FOXC2 mutations reveals small insertions and deletions throughout the gene. Hum Genet, 108, 546-51. https://doi.org/10.1007/s004390100528
- Benayoun BA, Caburet S, Veitia RA (2011). Forkhead transcription factors: key players in health and disease. Trends Genet, 27, 224-32. https://doi.org/10.1016/j.tig.2011.03.003
- Carlsson P, Mahlapuu M (2002). Forkhead transcription factors: key players in development and metabolism. Dev Biol, 250, 1-23. https://doi.org/10.1006/dbio.2002.0780
- Chen W, Yuan K, Tao ZZ, et al (2011). Deletion of Forkhead Box M1 transcription factor reduces malignancy in laryngeal squamous carcinoma cells. Asian Pac J Cancer Prev, 12, 1785-8.
- Crisponi L, Deiana M, Loi A, et al (2001). The putative forkhead transcription factor FOXL2 is mutated in blepharophimosis/ ptosis/epicanthus inversus syndrome. Nat Genet, 27, 159-66. https://doi.org/10.1038/84781
- Curtis C, Shah SP, Chin SF, et al (2012). The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. Nature, 486, 346-52.
- Dansen TB, Burgering BM (2008). Unravelling the tumorsuppressive functions of FOXO proteins. Trends Cell Biol, 18, 421-9. https://doi.org/10.1016/j.tcb.2008.07.004
- De BE, Dixon MJ, Small KW, et al (2001). Spectrum of FOXL2 gene mutations in blepharophimosis-ptosis-epicanthus inversus (BPES) families demonstrates a genotypephenotype correlation. Hum Mol Genet, 10, 1591-600. https://doi.org/10.1093/hmg/10.15.1591
- Dong XY, Chen C, Sun X, et al (2006). FOXO1A is a candidate for the 13q14 tumor suppressor gene inhibiting androgen receptor signaling in prostate cancer. Cancer Res, 66, 6998-7006. https://doi.org/10.1158/0008-5472.CAN-06-0411
- Lehmann OJ, Ebenezer ND, Jordan T, et al (2000). Chromosomal duplication involving the forkhead transcription factor gene FOXC1 causes iris hypoplasia and glaucoma. Am J Hum Genet, 67, 1129-35. https://doi.org/10.1016/S0002-9297(07)62943-7
- Lin L, Miller CT, Contreras JI, et al (2002). The hepatocyte nuclear factor 3 alpha gene, HNF3alpha (FOXA1), on chromosome band 14q13 is amplified and overexpressed in esophageal and lung adenocarcinomas. Cancer Res, 62, 5273-9.
- Lokody I (2014). Signalling: FOXM1 and CENPF: co-pilots driving prostate cancer. Nat Rev Cancer, 14, 450-1.
- Mazet F, Yu JK, Liberles DA, et al (2003). Phylogenetic relationships of the FOX (Forkhead) gene family in the Bilateria. Gene, 316, 79-89. https://doi.org/10.1016/S0378-1119(03)00741-8
- Nucera C, Eeckhoute J, Finn S, et al (2009). FOXA1 is a potential oncogene in anaplastic thyroid carcinoma. Clin Cancer Res, 15, 3680-9. https://doi.org/10.1158/1078-0432.CCR-08-3155
- Pohl BS, Knochel W (2005). Of FOX and Frogs: FOX (fork head/ winged helix) transcription factors in Xenopus development. Gene, 344, 21-32. https://doi.org/10.1016/j.gene.2004.09.037
- Sasahira T, Ueda N, Yamamoto K, et al (2014). Prox1 and FOXC2 act as regulators of lymphangiogenesis and angiogenesis in oral squamous cell carcinoma. PLoS One, 9, 92534. https://doi.org/10.1371/journal.pone.0092534
- Schneider J, Ruschhaupt M, Buness A, et al (2006). Identification and meta-analysis of a small gene expression signature for the diagnosis of estrogen receptor status in invasive ductal breast cancer. Int J Cancer, 119, 2974-9. https://doi.org/10.1002/ijc.22234
- Sulman EP, White PS, Brodeur GM (2004). Genomic annotation of the meningioma tumor suppressor locus on chromosome 1p34. Oncogene, 23, 1014-20. https://doi.org/10.1038/sj.onc.1206623
- Tu Q, Brown CT, Davidson EH, et al (2006). Sea urchin Forkhead gene family: phylogeny and embryonic expression. Dev Biol, 300, 49-62. https://doi.org/10.1016/j.ydbio.2006.09.031
- Wijchers PJ, Burbach JP, Smidt MP (2006). In control of biology: of mice, men and FOXes. Biochem J, 397, 233-46. https://doi.org/10.1042/BJ20060387
- Wotton KR, Shimeld SM (2006). Comparative genomics of vertebrate FOX cluster loci. BMC Genomics, 7, 271. https://doi.org/10.1186/1471-2164-7-271
- Xu N, Wu SD, Wang H, et al (2012). Involvement of FOXM1 in non-small cell lung cancer recurrence. Asian Pac J Cancer Prev, 13, 4739-43. https://doi.org/10.7314/APJCP.2012.13.9.4739
- Yang FQ, Yang FP, Li W, et al (2013). FOXl1 inhibits tumor invasion and predicts outcome in human renal cancer. Int J Clin Exp Pathol, 7, 110-22.
- Yu J, Deshmukh H, Payton JE, et al (2011). Array-based comparative genomic hybridization identifies CDK4 and FOXM1 alterations as independent predictors of survival in malignant peripheral nerve sheath tumor. Clin Cancer Res, 17, 1924-34. https://doi.org/10.1158/1078-0432.CCR-10-1551
- Zheng CH, Quan Y, Li YY, et al (2014). Expression of transcription factor FOXC2 in cervical cancer and effects of silencing on cervical cancer cell proliferation. Asian Pac J Cancer Prev, 15, 1589-95. https://doi.org/10.7314/APJCP.2014.15.4.1589