Study of the Expression of Pin1, β-Catenin and cycD1 Genes in Tumor Tissue of Patints with Colorectal Cancer
Authors
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Fatemeh Babajani
- Department of Clinical Biochemistry, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran.
https://orcid.org/0000-0001-6714-5309
-
Hosein Setayeshnia
- Department of Clinical Biochemistry, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran.
https://orcid.org/0009-0001-6718-0195
-
Hossien Mohammadi
- Department of Clinical Biochemistry, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran.
https://orcid.org/0000-0002-9485-2831
-
Hadi Mozafari
- Department of Clinical Biochemistry, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran.
https://orcid.org/0000-0003-4428-7675
-
Soheila Asadi*
- Department of Clinical Biochemistry, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran. - Fertility and Infertility Research Center, Health Technology Institute, Kermanshah University of Medical Science, Kermanshah, Iran.
https://orcid.org/0000-0003-2443-9221
DOI:
https://doi.org/10.22100/jkh.v20i3.3439Abstract
Introduction: This study investigated the expression of PIN1, β-catenin, and CycD1 genes in tumor and tumor-adjacent tissues of patients with CRC, as well as their correlations with the histopathological features of tumor tissues.
Methods: Thirty-one colorectal tumor samples and matched non-cancerous adjacent tissues were acquired from the Iran Tumor Bank/Tehran University of Medical Sciences. Gene expression of PIN1, β-catenin, and CycD1 was assessed using real-time PCR following RNA extraction and cDNA synthesis, and histopathological characteristics and their associations with gene expression were evaluated.
Results: Most patients were over 50 years old, with no history of alcohol use, non-smokers, and without a family history of CRC. In 83.9% of cases, tumors measured larger than 3 cm and were histologically classified as adenocarcinomas with a differentiation grade of 2. Vascular invasion was observed in 96.8% of cases, while lymphatic invasion was present in 93.5 %. The expression of PIN1 and β-catenin genes in tumor tissue was significantly increased compared to matched margin tissue (P=0.043 and P<0.0001, respectively). Also, the cycD1 gene expression increased in tumor tissue compared to the matched margin tissue, although this increase was not statistically significant. Furthermore, a direct and significant correlation was observed between the expression of PIN1 and CycD1 genes (P<0.001).
Conclusion: The results of this study suggest that PIN1 may influence the expression of β-catenin and Cyclin D1 in tumor tissues of CRC patients, indicating a potential role for this gene in the pathogenesis of CRC.
References
Biller LH, Schrag D. Diagnosis and treatment of metastatic colorectal cancer: a review. JAMA 2021;325:669-85. doi:10.1001/jama.2021.0106
Hossain MS, Karuniawati H, Jairoun AA, Urbi Z, Ooi J, John A, et al. Colorectal cancer: a review of carcinogenesis, global epidemiology, current challenges, risk factors, preventive and treatment strategies. Cancers 2022;14. doi:10.3390/cancers14071732
Murphy N, Moreno V, Hughes DJ, Vodicka L, Vodicka P, Aglago EK, et al. Lifestyle and dietary environmental factors in colorectal cancer susceptibility. Molecular Aspects of Medicine 2019;69:2-9. doi: 10.1016/j.mam.2019.06.005
Gholamzadeh Khoei S, Saidijam M, Amini R, Jalali A, Najafi R. Impact of PIN1 inhibition on tumor progression and chemotherapy sensitivity in colorectal cancer. Journal of Gastrointestinal Cancer 2022;1-12. doi: 10.1007/s12029-021-00600-6
Kim G, Bhattarai PY, Choi HS. Peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 as a molecular target in breast cancer: a therapeutic perspective of gynecological cancer. Archives of Pharmacal Research 2019;42:128-39. doi: 10.1007/s12272-019-01122-3
Cheng C-W, Tse E. PIN1 in cell cycle control and cancer. Frontiers in Pharmacology 2018;9:1367. doi: 10.3389/fphar.2018.01367
Kim CJ, Cho YG, Park YG, Nam SW, Kim SY, Lee SH, et al. Pin1 overexpression in colorectal cancer and its correlation with aberrant beta-catenin expression. World Journal of Gastroenterology 2005;11:5006-9. doi: 10.3748/wjg.v11.i32.5006
Stewart R, Sharma S, Wu T, Okuda S, Xie G, Zhou XZ, et al. The role of the master cancer regulator Pin1 in the development and treatment of cancer. Frontiers in cell and Developmental Biology 2024;12:1343938. doi: 10.3389/fcell.2024.1343938
The investigation of the role of Fas and FasL molecules in the extrinsic pathway of apoptosis as a target for cancer therapy in colorectal cancer. Clin Exc 2020;10:1-17.[Persian].
Jun SY, Kim J, Yoon N, Maeng LS, Byun JH. Prognostic potential of cyclin d1 expression in colorectal cancer. Journal of Clinical Medicine 2023;12. doi: 10.3390/jcm12020572
Mosaad H, Ahmed MM, Elaidy MM, Elfarargy OM, Abdelwahab MM, Abdelnour HM. Down-regulated MiRNA 29-b as a diagnostic marker in colorectal cancer and its correlation with ETV4 and Cyclin D1 immunohistochemical expression. Cancer Biomarkers: Section A of Disease Markers 2023;37:179-89. doi: 10.3233/CBM-220349
Rosen R, Sapra A. TNM Classification. StatPearls. Treasure Island (FL). Stat Pearls Publishing Copyright;2020.
Kuramochi J, Arai T, Ikeda S, Kumagai J, Uetake H, Sugihara K. High Pin1 expression is associated with tumor progression in colorectal cancer. Journal of Surgical Oncology 2006;94:155-60. doi: 10.1002/jso.20510
Wu W, Xue X, Chen Y, Zheng N, Wang J. Targeting prolyl isomerase Pin1 as a promising strategy to overcome resistance to cancer therapies. Pharmacological Research 2022;184:106456. doi: 10.1016/j.phrs.2022.106456
Gholamzadeh Khoei S, Saidijam M, Amini R, Jalali A, Najafi R. Impact of PIN1 inhibition on tumor progression and chemotherapy sensitivity in colorectal cancer. J Gastrointest Cancer 2022;53:299-310. doi: 10.1007/s12029-021-00600-6
Chen Y, Wu YR, Yang HY, Li XZ, Jie MM, Hu CJ, et al. Prolyl isomerase Pin1: a promoter of cancer and a target for therapy. Cell Death & Disease 2018;9:883. doi: 10.1038/s41419-018-0844-y
Yu JH, Im CY, Min SH. Function of PIN1 in cancer development and its inhibitors as cancer therapeutics. Frontiers in Cell and Developmental Biology 2020;8:120. doi: 10.3389/fcell.2020.00120
Ayala G, Wang D, Wulf G, Frolov A, Li R, Sowadski J, et al. The prolyl isomerase Pin1 is a novel prognostic marker in human prostate cancer. Cancer Research 2003;63:6244-51.
Liu J, Xiao Q, Xiao J, Niu C, Li Y, Zhang X, et al. Wnt/β-catenin signalling: function, biological mechanisms, and therapeutic opportunities. Signal Transduction and Targeted Therapy 2022;7:3. doi: 10.1038/s41392-021-00762-6
Fuchs SY, Ougolkov AV, Spiegelman VS, Minamoto T. Review oncogenic β-catenin signaling networks in colorectal cancer. Cell Cycle 2005;4:1522-39.
Fodde R. The APC gene in colorectal cancer. European Journal of Cancer 2002;38:867-71. doi: 10.1016/S0959-8049(02)00040-0
Zhao H, Ming T, Tang S, Ren S, Yang H, Liu M, et al. Wnt signaling in colorectal cancer: pathogenic role and therapeutic target. Molecular Cancer 2022;21:144. doi: 10.1186/s12943-022-01616-7
Wanitsuwan W, Kanngurn S, Boonpipattanapong T, Sangthong R, Sangkhathat S. Overall expression of beta-catenin outperforms its nuclear accumulation in predicting outcomes of colorectal cancers. World Journal of Gastroenterology 2008;14:6052-9. doi: 10.3748/wjg.14.6052
Utsunomiya T, Doki Y, Takemoto H, Shiozaki H, Yano M, Sekimoto M, et al. Correlation of beta-catenin and cyclin D1 expression in colon cancers. Oncology 2001;61:226-33. doi: 10.1159/000055379
Bian J, Dannappel M, Wan C, Firestein R. Transcriptional regulation of wnt/β-catenin pathway in colorectal cancer. Cells 2020;9. doi: 10.3390/cells9092125
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