The Potential Role of HDAC1 and HDAC3 Immunoexpression in P53 Downregulation and Tumor Aggressiveness of Colon and Rectum Carcinomas Patients

Authors

  • YASIR B. QADDOORI Department of Biology, College of Science, University of Baghdad, Baghdad, Iraq
  • AHMED S.K. AL-KHAFAJI Department of Biology, College of Science, University of Baghdad, Baghdad, Iraq
  • BASIM M. KHASHMAN Iraqi National Cancer Research Centre, University of Baghdad, Baghdad, Iraq
  • KIFAH H. ABDULGHAFOUR College of Medicine, University of Baghdad, Baghdad, Iraq

DOI:

https://doi.org/10.15407/exp-oncology.2024.04.393

Keywords:

colorectal cancer, TNM, expression, HDACs, P53

Abstract

Background. Colorectal cancer, ranking second place in global cancer mortality, arises from diverse causes. There is growing recognition of the substantial involvement of the epigenetic modifications of histones at the DNA level in the occurrence of CRC. Aim. To assess the expression of p53, HDAC1, and HDAC3 proteins in a cohort of CRC patients and to analyze potential relationship between their expression and the stages of CRC progression. Materials and Methods. The retrospective investigation was carried out on 95 paraffin-embedded CRC tissue samples. The expression of p53, HDAC1, and HDAC3 was assessed immunohistochemically. Results. Notably, the expression of the p53 protein in CRC tissue samples exhibited a prominent correlation with the protein expression of both HDAC1 (p < 0.001, rho = 0.522) and HDAC3 (p < 0.001, rho = 0.411), as well as the advanced TNM staging of CRC (p = 0.002, rho = 0.313). Downregulation of p53 was correlated with underexpressed HDAC1 and HDAC3. Nevertheless, the observed expression of p53 exhibited a significant negative correlation with the age of the patients. Conclusion. The data on HDACs-p53 co-expression suggest a possible mechanism of interaction between the expression of these proteins.

References

Kim DH, Pickhardt PJ. Chapter 3. Colorectal cancer: pathogenesis and risk factors. In: Pickhardt PJ, Kim DH, eds. CT Colonography: Principles and Practice of Virtual Colonoscopy. Philadelphia: W.B. Saunders, 2010:23-32.

Mustafa AJ, Balaky HM, Ismail PA. The role of adipocytokines, vitamin D, and C in colorectal cancer. Baghdad Sci J. 2023;20(3):0690. https://doi.org/10.21123/bsj.2022.7245

Shniakat W, Al-Khateeb E, Numan N, et al. Cytotoxic evaluation of doxorubicin combination with baicalein and res- veratrol against Hct116 and Hepg2 cancer cell lines (conference paper). Iraqi J Pharm Sci. 2023;31:92-99. https://doi. org/10.31351/vol31issSuppl.pp92-99

Klimeck L, Heisser T, Hoffmeister M, Brenner H. Colorectal cancer: a health and economic problem. Best Pract Res Clin Gastroenterol. 2023;66:101839. https://doi.org/10.1016/j.bpg.2023.101839

Mohammed HA, Kandala NJ. Evaluation of plasma-microRNA320 level among colorectal cancer Iraqi patients. Iraqi J Sci. 2023;64(3):1142-1150. https://doi.org/10.24996/ijs.2023.64.3.10

Lewandowska A, Rudzki G, Lewandowski T, et al. Risk factors for the diagnosis of colorectal cancer. Cancer Control. 2022;29:10732748211056692. https://doi.org/10.1177/10732748211056692

Sawicki T, Ruszkowska M, Danielewicz A, et al. A review of colorectal cancer in terms of epidemiology, risk factors, development, symptoms and diagnosis. Cancers. 2021;13(9):2025. https://doi.org/10.3390/cancers13092025

Farhad R, Saleh E, Alsammarraie A. Clinicopathological features of colorectal cancer in the iraqi population fo- cusing on age and early-onset of malignancy: a descriptive cross-sectional study. AJMS. 2023;5:86-91. https://doi. org/10.54133/ajms.v5i.158

Khalil KH, Al-Hassawi B, Abdo J. Correlation of neuroendocrine differentiation with neuroendocrine cell hyperpla- sia and vascular endothelial growth factor in colorectal adenocarcinoma. Baghdad Sci J. 2021;18(1):0018. https://doi. org/10.21123/bsj.2021.18.1.0018

Nadir FA, Ali ZA. Evaluating the levels of tumor necrosis factor-α, interleukin-6 and vascular endothelial growth factor in patients with colorectal cancer. Iraqi J Sci. 2023;64(10):4902-4910. https://doi.org/10.24996/ijs.2023.64.10.1

Naidu BP, Pallaval Veera B. mtDNA Haplogroup M5 associated with risk of colorectal cancer in south india popula- tion. Iraqi J Sci. 2021;62(6):1863-1872. https://doi.org/10.24996/ijs.2021.62.6.12

Abbas SM, Dhahi MAR, Muhammad SH. Evaluation of gene expression level of miRNA-29c, miRNA-125, miR- NA-141, miRNA-145 and miRNA-205 as predisposing factors for transitional cell carcinoma-bladder cancer in iraqi patients. Iraqi J Sci. 2023;64(8):3799-3811. https://doi.org/10.24996/ijs.2023.64.8.7

Moreta-Moraleda C, Queralt C, Vendrell-Ayats C, et al. Chromatin factors: Ready to roll as biomarkers in metastatic colorectal cancer? Pharmacol Res. 2023;196:106924. https://doi.org/10.1016/j.phrs.2023.106924

Lao VV, Grady WM. Epigenetics and colorectal cancer. Nat Rev Gastroenterol Hepatol. 2011;8(12):686-700. https:// doi.org/10.1038/nrgastro.2011.173

Yousif A. Revision of some Biomarkers with cytokines in breast cancer. Baghdad Sci J. 2023;20(1):0026. https://doi. org/10.21123/bsj.2022.6797

Hade I, Al-Khafaji A, Lafta F. Involvement of total antioxidant activity and eNOS gene rs1799983/ rs2070744 poly- morphisms in breast carcinogenesis. Iraqi J Sci. 2024:65(3):1297-1309. https://doi.org/10.24996/ijs.2024.65.3.11

Liu R, Wu J, Guo H, et al. Post-translational modifications of histones: Mechanisms, biological functions, and thera- peutic targets. MedComm (2020). 2023;4(3):e292. https://doi.org/10.1002/mco2.292

Wang Z, Qin G, Zhao TC. HDAC4: mechanism of regulation and biological functions. Epigenomics. 2014;6(1):139- 150. https://doi.org/10.2217/epi.13.73

Wang J, Yun F, Sui J, et al. HAT- and HDAC-targeted protein acetylation in the occurrence and treatment of epilepsy.

Biomedicines. 2022;11(1):88. https://doi.org/10.3390/biomedicines11010088

Swaroop S, Batabyal A, Bhattacharjee A. HAT/HDAC: the epigenetic regulators of inflammatory gene expression (Review). Int J Epigen. 2021;1(2):5. https://doi.org/10.3892/ije.2021.5

Pouloudi D, Manou M, Sarantis P, et al. Clinical significance of histone deacetylase (HDAC)-1, -2, -4 and -6 expres- sion in salivary gland tumors. Diagnostics (Basel). 2021;11(3):517. https://doi.org/10.3390/diagnostics11030517

Alazzawi AA, Ghaloub AN, Yaaqoob LA. Investigating the antioxidant and apoptosis inducing effects of biologi- cally synthesized silver nanoparticles against lymphoma cells in vitro. Iraqi J Sci. 2023;64(9):4390-4403. https://doi. org/10.24996/ijs.2023.64.9.9

Levine AJ. The many faces of p53: something for everyone. J Mol Cell Biol. 2019;11(7):524-530. https://doi. org/10.1093/jmcb/mjz026

Altaee MF, Abed RM, Samawi FT. In vivo and in vitro study of the genetic effects of cabergoline drug. Iraqi J Sci. 2021;62(5):1477-1483. https://doi.org/10.24996/ijs.2021.62.5.11

Marei HE, Althani A, Afifi N, et al. p53 signaling in cancer progression and therapy. Cancer Cell Int. 2021;21(1):703. https://doi.org/10.1186/s12935-021-02396-8

Li XL, Zhou J, Chen ZR, Chng WJ. P53 mutations in colorectal cancer — molecular pathogenesis and pharmacologi- cal reactivation. World J Gastroenterol. 2015;21(1):84-93. https://doi.org/10.3748/wjg.v21.i1.84

Yang H, Salz T, Zajac-Kaye M, et al. Overexpression of histone deacetylases in cancer cells is controlled by interplay of transcription factors and epigenetic modulators. FASEB J. 2014;28(10):4265-4279. https://doi.org/10.1096/fj.14- 250654

Mrakovcic M, Kleinheinz J, Fröhlich LF. p53 at the crossroads between different types of hdac inhibitor-mediated cancer cell death. Int J Mol Sci. 2019;20(10):2415. https://doi.org/10.3390/ijms20102415

Shanmugam G, Rakshit S, Sarkar K. HDAC inhibitors: targets for tumor therapy, immune modulation and lung diseases. Transl Oncol. 2022;16:101312. https://doi.org/10.1016/j.tranon.2021.101312

Weiser MR. AJCC 8th edition: colorectal cancer. Ann Surg Oncol. 2018;25(6):1454-1455. https://doi.org/10.1245/ s10434-018-6462-1

Ismael M, Qaddoori Y, Shaban M, Al-Rubaii B. The immunohistochemical staining of vimentin and E-cadherin in bladder cancer patients infected with Hepatitis C virus. JPAM. 2023;17(2):1009-1016. https://doi.org/10.22207/ JPAM.17.2.30

Fedchenko N, Reifenrath J. Different approaches for interpretation and reporting of immunohistochemistry analysis results in the bone tissue — a review. Diag Pathol. 2014;9(1):221. https://doi.org/10.1186/s13000-014-0221-9

Bartha Á, Győrffy B. TNMplot.com: A web tool for the comparison of gene expression in normal, tumor and meta- static tissues. Int J Mol Sci. 2021;22(5):2622. https://doi.org/10.3390/ijms22052622

Lánczky A, Győrffy B. Web-based survival analysis tool tailored for medical research (KMplot): development and implementation. J Med Internet Res. 2021;23(7):e27633. https://doi.org/10.2196/27633

Krishnamurthy J, Ramsey MR, Ligon KL, et al. p16INK4a induces an age-dependent decline in islet regenerative potential. Nature. 2006;443(7110):453-457. https://doi.org/10.1038/nature05092

Woodland DL, Blackman MA. Immunity and age: living in the past? Trends Immunol. 2006;27(7):303-307. https:// doi.org/10.1016/j.it.2006.05.002

Kim RH, Kang MK, Kim T, et al. Regulation of p53 during senescence in normal human keratinocytes. Aging Cell. 2015;14(5):838-846. https://doi.org/10.1111/acel.12364

Feng Z, Hu W, Teresky AK, et al. Declining p53 function in the aging process: a possible mechanism for the increased tumor incidence in older populations. Proc Natl Acad Sci USA. 2007;104(42):16633-16638. https://doi.org/10.1073/ pnas.0708043104

Wang P, Liang J, Wang Z, et al. The prognostic value of p53 positive in colorectal cancer: A retrospective cohort study.

Tumour Biol. 2017;39(5):1010428317703651. https://doi.org/10.1177/1010428317703651

Moldvay J, Strausz J, EgervÁry M, et al. P53 expression in stage I squamous cell lung cancer. Pathol Oncol Res. 1998;4(1):8-13. https://doi.org/10.1007/BF02904688

Yang P, Du CW, Kwan M, et al. The impact of p53 in predicting clinical outcome of breast cancer patients with vis- ceral metastasis. Sci Rep. 2013;3(1):2246. https://doi.org/10.1038/srep02246

Liebl MC, Hofmann TG. The role of p53 signaling in colorectal cancer. Cancers. 2021;13(9):2125. https://doi. org/10.3390/cancers13092125

Ito A, Kawaguchi Y, Lai CH, et al. MDM2-HDAC1-mediated deacetylation of p53 is required for its degradation.

EMBO J. 2002;21(22):6236-6245. https://doi.org/10.1093/emboj/cdf616

Zhang F, Shi Y, Wang L, Sriram S. Role of HDAC3 on p53 expression and apoptosis in T cells of patients with multiple sclerosis. PLoS One. 2011;6(2):e16795. https://doi.org/10.1371/journal.pone.0016795

Zhou L, Xu X, Liu H, et al. Prognosis analysis of histone deacetylases mRNA expression in ovarian cancer patients.

J Cancer. 2018;9(23):4547-4555. https://doi.org/10.7150/jca.26780

Yan W, Liu S, Xu E, et al. Histone deacetylase inhibitors suppress mutant p53 transcription via histone deacetylase 8.

Oncogene. 2013;32(5):599-609. https://doi.org/10.1038/onc.2012.81

Kim KM, Ahn A-R, Park HS, et al. Clinical significance of p53 protein expression and TP53 variation status in colorectal cancer. BMC Cancer. 2022;22(1):940. https://doi.org/10.1186/s12885-022-10039-y

Brooks CL, Gu W. The impact of acetylation and deacetylation on the p53 pathway. Protein Cell. 2011;2(6):456-462. https://doi.org/10.1007/s13238-011-1063-9

Al-Khafaji ASK, Wang LM, Alabdei HH, Liloglou T. Effect of valproic acid on histone deacetylase expression in oral cancer (Review). Oncol Lett. 2024;27(5):197. https://doi.org/10.3892/ol.2024.14330

Juan L-J, Shia W-J, Chen M-H, et al. Histone deacetylases specifically down-regulate p53-dependent gene activation.

J Biol Chem. 2000;275(27):20436-20443. https://doi.org/10.1074/jbc.M000202200

Downloads

Published

12.12.2024

How to Cite

QADDOORI, Y. B., AL-KHAFAJI, A. S., KHASHMAN, B. M., & ABDULGHAFOUR, K. H. (2024). The Potential Role of HDAC1 and HDAC3 Immunoexpression in P53 Downregulation and Tumor Aggressiveness of Colon and Rectum Carcinomas Patients. Experimental Oncology, 46(4), 393–401. https://doi.org/10.15407/exp-oncology.2024.04.393

Issue

Section

Original contributions