Acetylated HOXB9 at lysine 27 is of differential diagnostic value in patients with pancreatic ductal adenocarcinoma

Xiaoran Sun , Jiagui Song , Jing Zhang , Jun Zhan , Weigang Fang , Hongquan Zhang

Front. Med. ›› 2020, Vol. 14 ›› Issue (1) : 91 -100.

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Front. Med. ›› 2020, Vol. 14 ›› Issue (1) : 91 -100. DOI: 10.1007/s11684-019-0696-6
RESEARCH ARTICLE
RESEARCH ARTICLE

Acetylated HOXB9 at lysine 27 is of differential diagnostic value in patients with pancreatic ductal adenocarcinoma

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Abstract

Pancreatic ductal adenocarcinoma (PDAC) is the ninth most common human malignancy and the sixth leading cause of cancer-related death in China. AcK27-HOXB9 is a newly identified HOXB9 post-transcriptional modification that can predict the outcome in lung adenocarcinoma and colon cancer well. However, the role of AcK27-HOXB9 in PDAC is unclear. The present study aims to investigate the differential diagnostic role of patients with AcK27-HOXB9 PDAC. Tissue microarrays consisting of 162 pancreatic tumor tissue samples from patients with PDAC and paired normal subjects were used to examine HOXB9 and AcK27-HOXB9 levels and localizations by immunohistochemical analysis and Western blot assay, respectively. HOXB9 was upregulated (P<0.0001), and AcK27-HOXB9 (P=0.0023) was downregulated in patients with PDAC. HOXB9 promoted (P=0.0115), while AcK27-HOXB9 (P=0.0279) inhibited PDAC progression. AcK27-HOXB9 predicted favorable outcome in patients with PDAC (P=0.0412). AcK27-HOXB9 also suppressed PDAC cell migration in a cell migration assay. The results of this study showed that HOXB9 promoted and AcK27-HOXB9 suppressed PDAC progression. The determination of ratio between HOXB9 and AcK27-HOXB9 exhibited potential diagnostic value in patients with PDAC.

Keywords

HOXB9 / AcK27-HOXB9 / PDAC

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Xiaoran Sun, Jiagui Song, Jing Zhang, Jun Zhan, Weigang Fang, Hongquan Zhang. Acetylated HOXB9 at lysine 27 is of differential diagnostic value in patients with pancreatic ductal adenocarcinoma. Front. Med., 2020, 14(1): 91-100 DOI:10.1007/s11684-019-0696-6

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References

[1]

Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ, He J. Cancer statistics in China, 2015. CA Cancer J Clin 2016; 66(2): 115–132

[2]

Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res 2014; 74(11): 2913–2921

[3]

Oettle H, Neuhaus P, Hochhaus A, Hartmann JT, Gellert K, Ridwelski K, Niedergethmann M, Zülke C, Fahlke J, Arning MB, Sinn M, Hinke A, Riess H. Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial. JAMA 2013; 310(14): 1473–1481

[4]

Regine WF, Winter KA, Abrams RA, Safran H, Hoffman JP, Konski A, Benson AB, Macdonald JS, Kudrimoti MR, Fromm ML, Haddock MG, Schaefer P, Willett CG, Rich TA. Fluorouracil vs gemcitabine chemotherapy before and after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma: a randomized controlled trial. JAMA 2008; 299(9): 1019–1026

[5]

Garcia-Fernàndez J. The genesis and evolution of homeobox gene clusters. Nat Rev Genet 2005; 6(12): 881–892

[6]

Abate-Shen C. Deregulated homeobox gene expression in cancer: cause or consequence? Nat Rev Cancer 2002; 2(10): 777–785

[7]

Chang Q, Zhang L, He C, Zhang B, Zhang J, Liu B, Zeng N, Zhu Z. HOXB9 induction of mesenchymal-to-epithelial transition in gastric carcinoma is negatively regulated by its hexapeptide motif. Oncotarget 2015; 6(40): 42838–42853

[8]

Wu SY, Rupaimoole R, Shen F, Pradeep S, Pecot CV, Ivan C, Nagaraja AS, Gharpure KM, Pham E, Hatakeyama H, McGuire MH, Haemmerle M, Vidal-Anaya V, Olsen C, Rodriguez-Aguayo C, Filant J, Ehsanipour EA, Herbrich SM, Maiti SN, Huang L, Kim JH, Zhang X, Han HD, Armaiz-Pena GN, Seviour EG, Tucker S, Zhang M, Yang D, Cooper LJ, Ali-Fehmi R, Bar-Eli M, Lee JS, Ram PT, Baggerly KA, Lopez-Berestein G, Hung MC, Sood AK. A miR-192-EGR1-HOXB9 regulatory network controls the angiogenic switch in cancer. Nat Commun 2016; 7(1): 11169

[9]

Hayashida T, Takahashi F, Chiba N, Brachtel E, Takahashi M, Godin-Heymann N, Gross KW, Vivanco M, Wijendran V, Shioda T, Sgroi D, Donahoe PK, Maheswaran S. HOXB9, a gene overexpressed in breast cancer, promotes tumorigenicity and lung metastasis. Proc Natl Acad Sci USA 2010; 107(3): 1100–1105

[10]

Kelly Z, Moller-Levet C, McGrath S, Butler-Manuel S, Kavitha Madhuri T, Kierzek AM, Pandha H, Morgan R, Michael A. The prognostic significance of specific HOX gene expression patterns in ovarian cancer. Int J Cancer 2016; 139(7): 1608–1617

[11]

Zhan J, Wang P, Niu M, Wang Y, Zhu X, Guo Y, Zhang H. High expression of transcriptional factor HoxB9 predicts poor prognosis in patients with lung adenocarcinoma. Histopathology 2015; 66(7): 955–965

[12]

Wan J, Liu H, Feng Q, Liu J, Ming L. HOXB9 promotes endometrial cancer progression by targeting E2F3. Cell Death Dis 2018; 9(5): 509

[13]

Wan J, Xu W, Zhan J, Ma J, Li X, Xie Y, Wang J, Zhu WG, Luo J, Zhang H. PCAF-mediated acetylation of transcriptional factor HOXB9 suppresses lung adenocarcinoma progression by targeting oncogenic protein JMJD6. Nucleic Acids Res 2016; 44(22): 10662–10675

[14]

Song J, Wang T, Xu W, Wang P, Wan J, Wang Y, Zhan J, Zhang H. HOXB9 acetylation at K27 is responsible for its suppression of colon cancer progression. Cancer Lett 2018; 426: 63–72

[15]

Chen C, Sun X, Ran Q, Wilkinson KD, Murphy TJ, Simons JW, Dong JT. Ubiquitin-proteasome degradation of KLF5 transcription factor in cancer and untransformed epithelial cells. Oncogene 2005; 24(20): 3319–3327

[16]

Grier DG, Thompson A, Kwasniewska A, McGonigle GJ, Halliday HL, Lappin TR. The pathophysiology of HOX genes and their role in cancer. J Pathol 2005; 205(2): 154–171

[17]

Chen H, Sukumar S. HOX genes: emerging stars in cancer. Cancer Biol Ther 2003; 2(5): 524–525

[18]

Rhoads K, Arderiu G, Charboneau A, Hansen SL, Hoffman W, Boudreau N. A role for HOx A5 in regulating angiogenesis and vascular patterning. Lymphat Res Biol 2005; 3(4): 240–252

[19]

Fromental-Ramain C, Warot X, Lakkaraju S, Favier B, Haack H, Birling C, Dierich A, Doll e P, Chambon P. Specific and redundant functions of the paralogous Hoxa-9 and Hoxd-9 genes in forelimb and axial skeleton patterning. Development 1996; 122(2): 461–472

[20]

Chen F, Capecchi MR. Paralogous mouse Hox genes, Hoxa9, Hoxb9, and Hoxd9, function together to control development of the mammary gland in response to pregnancy. Proc Natl Acad Sci USA 1999; 96(2): 541–546

[21]

Sha S, Gu Y, Xu B, Hu H, Yang Y, Kong X, Wu K. Decreased expression of HOXB9 is related to poor overall survival in patients with gastric carcinoma. Dig Liver Dis 2013; 45: 422–429

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