Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74:229–63.
Borkar S, Reche A, Paul P, Deshpande A, Deshpande M. Noninvasive technique for the screening and diagnosis of oral squamous cell carcinoma. Cureus. 2023;15:e46300.
Padam KSR, Morgan R, Hunter K, Chakrabarty S, Kumar NAN, Radhakrishnan R. Identification of HOX signatures contributing to oral cancer phenotype. Sci Rep. 2022;12:10123.
Rodini CO, Xavier FC, Paiva KB, De Souza Setubal Destro MF, Moyses RA, Michaluarte P, et al. Homeobox gene expression profile indicates HOXA5 as a candidate prognostic marker in oral squamous cell carcinoma. Int J Oncol. 2012;40:1180–8.
Tucci R, Campos MS, Matizonkas-Antonio LF, Durazzo M, Pinto Junior Ddos S, Nunes FD. HOXB5 expression in oral squamous cell carcinoma. J Appl Oral Sci. 2011;19:125–9.
Platais C, Hakami F, Darda L, Lambert DW, Morgan R, Hunter KD. The role of HOX genes in head and neck squamous cell carcinoma. J Oral Pathol Med. 2016;45:239–47.
Ferrier DE, Holland PW. Ancient origin of the Hox gene cluster. Nat Rev Genet. 2001;2:33–8.
Holland PW. Evolution of homeobox genes. Wiley Interdiscip Rev Dev Biol. 2013;2:31–45.
Montavon T, Duboule D. Chromatin organization and global regulation of Hox gene clusters. Philos Trans R Soc Lond B Biol Sci. 2013;368:20120367.
Ozernyuk N, Schepetov D. HOX-gene cluster organization and genome duplications in fishes and mammals: transcript variant distribution along the anterior-posterior axis. Int J Mol Sci. 2022;23:9990.
Collins CT, Hess JL. Role of HOXA9 in leukemia: dysregulation, cofactors and essential targets. Oncogene. 2016;35:1090–8.
Cai H, Ke ZB, Dong RN, Chen H, Lin F, Zheng WC, et al. The prognostic value of homeobox A9 (HOXA9) methylation in solid tumors: a systematic review and meta-analysis. Transl Cancer Res. 2021;10:4347–54.
Wellik DM. Hox patterning of the vertebrate axial skeleton. Dev Dyn. 2007;236:2454–63.
Fromental-Ramain C, Warot X, Lakkaraju S, Favier B, Haack H, Birling C, et al. Specific and redundant functions of the paralogous Hoxa-9 and Hoxd-9 genes in forelimb and axial skeleton patterning. Development. 1996;122:461–72.
Xu B, Geerts D, Bu Z, Ai J, Jin L, Li Y, et al. Regulation of endometrial receptivity by the highly expressed HOXA9, HOXA11 and HOXD10 HOX-class homeobox genes. Hum Reprod. 2014;29:781–90.
Yan J, Chen YX, Desmond A, Silva A, Yang Y, Wang H, et al. Cdx4 and menin co-regulate Hoxa9 expression in hematopoietic cells. PLoS ONE. 2006;1:e47.
Patel CV, Sharangpani R, Bandyopadhyay S, DiCorleto PE. Endothelial cells express a novel, tumor necrosis factor-alpha-regulated variant of HOXA9. J Biol Chem. 1999;274:1415–22.
Di-Poi N, Koch U, Radtke F, Duboule D. Additive and global functions of HoxA cluster genes in mesoderm derivatives. Dev Biol. 2010;341:488–98.
Raines AM, Magella B, Adam M, Potter SS. Key pathways regulated by HoxA9,10,11/HoxD9,10,11 during limb development. BMC Dev Biol. 2015;15:28.
Tang L, Peng L, Tan C, Liu H, Chen P, Wang H. Role of HOXA9 in solid tumors: mechanistic insights and therapeutic potential. Cancer Cell Int. 2022;22:349.
Alvarado-Ruiz L, Martinez-Silva MG, Torres-Reyes LA, Pina-Sanchez P, Ortiz-Lazareno P, Bravo-Cuellar A, et al. HOXA9 is underexpressed in cervical cancer cells and its restoration decreases proliferation, migration and expression of epithelial-to-mesenchymal transition genes. Asian Pac J Cancer Prev. 2016;17:1037–47.
Sun M, Song CX, Huang H, Frankenberger CA, Sankarasharma D, Gomes S, et al. HMGA2/TET1/HOXA9 signaling pathway regulates breast cancer growth and metastasis. Proc Natl Acad Sci USA. 2013;110:9920–5.
Wang X, Bu J, Liu X, Wang W, Mai W, Lv B, et al. miR-133b suppresses metastasis by targeting HOXA9 in human colorectal cancer. Oncotarget. 2017;8:63935–48.
Xavier-Magalhaes, Goncalves A, Fogli CS, Lourenco T A, Pojo M, Pereira B, et al. The long non-coding RNA HOTAIR is transcriptionally activated by HOXA9 and is an independent prognostic marker in patients with malignant glioma. Oncotarget. 2018;9:15740–56.
Goncalves CS, Xavier-Magalhaes A, Martins EP, Pinto AA, Pires MM, Pinheiro C, et al. A novel molecular link between HOXA9 and WNT6 in glioblastoma identifies a subgroup of patients with particular poor prognosis. Mol Oncol. 2020;14:1224–41.
Zhou L, Wang Y, Zhou M, Zhang Y, Wang P, Li X, et al. HOXA9 inhibits HIF-1alpha-mediated glycolysis through interacting with CRIP2 to repress cutaneous squamous cell carcinoma development. Nat Commun. 2018;9:1480.
Han S, Li X, Liang X, Zhou L. HOXA9 transcriptionally promotes apoptosis and represses autophagy by targeting NF-kappaB in cutaneous squamous cell carcinoma. Cells. 2019;8:1360.
Wang Z, Yu C, Wang H. HOXA5 inhibits the proliferation and induces the apoptosis of cervical cancer cells via regulation of protein kinase B and p27. Oncol Rep. 2019;41:1122–30.
Kendziorra E, Ahlborn K, Spitzner M, Rave-Frank M, Emons G, Gaedcke J, et al. Silencing of the Wnt transcription factor TCF4 sensitizes colorectal cancer cells to (chemo-) radiotherapy. Carcinogenesis. 2011;32:1824–31.
Faaborg L, Jakobsen A, Waldstrom M, Petersen CB, Andersen RF, Steffensen KD. HOXA9-methylated DNA as a diagnostic biomarker of ovarian malignancy. Biomark Med. 2021;15:1309–17.
Zhou C, Li J, Li Q, Liu H, Ye D, Wu Z, et al. The clinical significance of HOXA9 promoter hypermethylation in head and neck squamous cell carcinoma. J Clin Lab Anal. 2019;33:e22873.
Park SM, Choi EY, Bae M, Choi JK, Kim YJ. A long-range interactive DNA methylation marker panel for the promoters of HOXA9 and HOXA10 predicts survival in breast cancer patients. Clin Epigenetics. 2017;9:73.
Xu Q, Zhang Q, Dong M, Yu Y. MicroRNA-638 inhibits the progression of breast cancer through targeting HOXA9 and suppressing Wnt/beta-cadherin pathway. World J Surg Oncol. 2021;19:247.
Xu C, Li B, Zhao S, Jin B, Jia R, Ge J, et al. MicroRNA-186-5p inhibits proliferation and metastasis of esophageal cancer by mediating HOXA9. Onco Targets Ther. 2019;12:8905–14.
Wang SM, Pang J, Zhang KJ, Zhou ZY, Chen FY. lncRNA MIR503HG inhibits cell proliferation and promotes apoptosis in TNBC cells via the miR-224-5p/HOXA9 axis. Mol Ther Oncolytics. 2021;21:62–73.
Sun Q, Zhang SY, Zhao JF, Han XG, Wang HB, Sun ML. HIF-1alpha or HOTTIP/CTCF promotes head and neck squamous cell carcinoma progression and drug resistance by targeting HOXA9. Mol Ther Nucleic Acids. 2020;20:164–75.
Uchida K, Veeramachaneni R, Huey B, Bhattacharya A, Schmidt BL, Albertson DG. Investigation of HOXA9 promoter methylation as a biomarker to distinguish oral cancer patients at low risk of neck metastasis. BMC Cancer. 2014;14:353.
Guerrero-Preston R, Soudry E, Acero J, Orera M, Moreno-Lopez L, Macia-Colon G, et al. NID2 and HOXA9 promoter hypermethylation as biomarkers for prevention and early detection in oral cavity squamous cell carcinoma tissues and saliva. Cancer Prev Res. 2011;4:1061–72.
Xiong L, Wu F, Wu Q, Xu L, Cheung OK, Kang W, et al. Aberrant enhancer hypomethylation contributes to hepatic carcinogenesis through global transcriptional reprogramming. Nat Commun. 2019;10:335.
Gehring A, Huebner K, Rani H, Erlenbach-Wuensch K, Merkel S, Mahadevan V, et al. DNA demethylation and tri-methylation of H3K4 at the TACSTD2 promoter are complementary players for TROP2 regulation in colorectal cancer cells. Sci Rep. 2024;14:2683.
Malek R, Gajula RP, Williams RD, Nghiem B, Simons BW, Nugent K, et al. TWIST1-WDR5-hottip regulates Hoxa9 chromatin to facilitate prostate cancer metastasis. Cancer Res. 2017;77:3181–93.
Vesuna F, van Diest P, Chen JH, Raman V. Twist is a transcriptional repressor of E-cadherin gene expression in breast cancer. Biochem Biophys Res Commun. 2008;367:235–41.
Wong TS, Gao W, Chan JY. Transcription regulation of E-cadherin by zinc finger E-box binding homeobox proteins in solid tumors. Biomed Res Int. 2014;2014:921564.
Gilbert PM, Mouw JK, Unger MA, Lakins JN, Gbegnon MK, Clemmer VB, et al. HOXA9 regulates BRCA1 expression to modulate human breast tumor phenotype. J Clin Investig. 2010;120:1535–50.
Chong GO, Jeon HS, Han HS, Son JW, Lee YH, Hong DG, et al. Overexpression of microRNA-196b accelerates invasiveness of cancer cells in recurrent epithelial ovarian cancer through regulation of homeobox A9. Cancer Genomics Proteomics. 2017;14:137–41.
Ooki A, Maleki Z, Tsay JJ, Goparaju C, Brait M, Turaga N, et al. A panel of novel detection and prognostic methylated DNA markers in primary non-small cell lung cancer and serum dnA. Clin Cancer Res. 2017;23:7141–52.
Gao L, Yan SB, Yang J, Kong JL, Shi K, Ma FC, et al. MiR-182-5p and its target HOXA9 in non-small cell lung cancer: a clinical and in-silico exploration with the combination of RT-qPCR, miRNA-seq and miRNA-chip. BMC Med Genomics. 2020;13:3.
Lissa D, Ishigame T, Noro R, Tucker MJ, Bliskovsky V, Shema S, et al. HOXA9 methylation and blood vessel invasion in FFPE tissues for prognostic stratification of stage I lung adenocarcinoma patients. Lung Cancer. 2018;122:151–9.
Xia Z, Yang C, Yang X, Wu S, Feng Z, Qu L, et al. miR-652 promotes proliferation and migration of uveal melanoma cells by targeting HOXA9. Med Sci Monit. 2019;25:8722–32.
Zhang ZF, Li GR, Cao CN, Xu Q, Wang GD, Jiang XF. MicroRNA-1294 targets HOXA9 and has a tumor suppressive role in osteosarcoma. Eur Rev Med Pharmacol Sci. 2018;22:8582–8.
Ma YY, Zhang Y, Mou XZ, Liu ZC, Ru GQ, Li E. High level of homeobox A9 and PBX homeobox 3 expression in gastric cancer correlates with poor prognosis. Oncol Lett. 2017;14:5883–9.
Fu Z, Chen C, Zhou Q, Wang Y, Zhao Y, Zhao X, et al. LncRNA HOTTIP modulates cancer stem cell properties in human pancreatic cancer by regulating HOXA9. Cancer Lett. 2017;410:68–81.
Watanabe Y, Saito M, Saito K, Matsumoto Y, Kanke Y, Onozawa H, et al. Upregulated HOXA9 expression is associated with lymph node metastasis in colorectal cancer. Oncol Lett. 2018;15:2756–62.
Osmond B, Facey COB, Zhang C, Boman BM. HOXA9 overexpression contributes to stem cell overpopulation that drives development and growth of colorectal cancer. Int J Mol Sci. 2022;23.
Liu T, Ji C, Sun Y, Bai W. HOXA9 expression is associated with advanced tumour stage and prognosis in nasopharyngeal carcinoma. Cancer Manag Res. 2021;13:4147–54.
Sun X, Liu B, Ji W, Ma X, Wang X, Gu H. The role of HOXA9 in human laryngeal squamous cell carcinoma. Oncol Res. 2013;20:467–72.
Zhan T, Rindtorff N, Boutros M. Wnt signaling in cancer. Oncogene. 2017;36:1461–73.
Xue W, Yang L, Chen C, Ashrafizadeh M, Tian Y, Sun R. Wnt/beta-catenin-driven EMT regulation in human cancers. Cell Mol Life Sci. 2024;81:79.
Padala RR, Karnawat R, Viswanathan SB, Thakkar AV, Das AB. Cancerous perturbations within the ERK, PI3K/Akt, and Wnt/beta-catenin signaling network constitutively activate inter-pathway positive feedback loops. Mol Biosyst. 2017;13:830–40.
Cai F, Li J, Zhang Y, Huang S, Liu W, Zhuo W, et al. Interaction between Wnt/beta-catenin signaling pathway and EMT pathway mediates the mechanism of sunitinib resistance in renal cell carcinoma. BMC Cancer. 2024;24:175.
Wang K, Jin J, Ma T, Zhai H. MiR-139-5p inhibits the tumorigenesis and progression of oral squamous carcinoma cells by targeting HOXA9. J Cell Mol Med. 2017;21:3730–40.
Mei B, Zeng Z, Xia Q, Liu M, Zhang Y. The role of the circ_DOCK1-miR-1297-HOXA9 regulatory network in the development of oral squamous cell carcinoma. Pathol Res Pract. 2025;266:155752.
Wang X, Shen J, Wang L, Deng L, Bo H, Luo Y, et al. DNA hypomethylation and upregulated LINC00518 acts as a promoter and biomarker in head and neck squamous cell carcinoma. Epigenomics. 2023;15:293–306.
Hou X, Liao Q, Wu Y, Wang L, Zhao J, Liao X. Hypomethylation-mediated upregulation of NFE2L3 promotes malignant phenotypes of clear cell renal cell carcinoma cells. Mol Biotechnol. 2024;66:198–207.
Dickson MA, Hahn WC, Ino Y, Ronfard V, Wu JY, Weinberg RA, et al. Human keratinocytes that express hTERT and also bypass a p16(INK4a)-enforced mechanism that limits life span become immortal yet retain normal growth and differentiation characteristics. Mol Cell Biol. 2000;20:1436–47.
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25:402–8.
Lee BT, Barber GP, Benet-Pages A, Casper J, Clawson H, Diekhans M, et al. The UCSC Genome Browser database: 2022 update. Nucleic Acids Res. 2022;50:D1115–D22.
Dreos R, Ambrosini G, Perier RC, Bucher P. The eukaryotic promoter database: expansion of EPDnew and new promoter analysis tools. Nucleic Acids Res. 2015;43:D92–6.
Messeguer X, Escudero R, Farre D, Nunez O, Martinez J, Alba MM. PROMO: detection of known transcription regulatory elements using species-tailored searches. Bioinformatics. 2002;18:333–4.
Andersson R, Gebhard C, Miguel-Escalada I, Hoof I, Bornholdt J, Boyd M, et al. FastQC: A quality control tool for high throughput sequence data. Version. 2010;011:2.
Zheng R, Wan C, Mei S, Qin Q, Wu Q, Sun H, et al. Cistrome data browser: expanded datasets and new tools for gene regulatory analysis. Nucleic Acids Res. 2019;47:D729–D35.

