Association between prostate cancer development and TARBP1
DOI:
https://doi.org/10.24079/CAJMS.2025.01.004Keywords:
TARBP1, Prostate cancer, LNCaP, LV-shTARBP1Abstract
Objective: Prostate cancer is the most frequent cancer among elderly men worldwide and second cause of cancer-related deaths in man. Prostate cancer characterized a clinically heterogeneous and genetic alterations in cells play a pivotal role in carcinogenesis. A detailed understandings of the genetic alterations in cancer cells are important for developing new therapeutic medicine. Transactivation response RNA-binding protein1 (TARBP1) encodes a protein with RNA-binding, tRNA methyltransferase activity, and RNA interference regulation functions, but its association with prostate cancer remains unclear. The aim of this study was to investigate clinical significance of TARBP1 in prostate cancer. Methods: Relative messenger ribonucleic acid (mRNA) and protein expression of TARBP1 in prostate cancer cell and tumor tissue was determined by qRT-PCR and Western blot analysis. LNCaP cells with lentivirus vector to silence the expression of TARBP1 were injected into nude mice. After 24 days, the mice were killed and tumor tissues were excised. The size of tumors was measured using a ruler and body weight of mice were weighed using a scale. Results: Through qRT-PCR and Western blot analysis, we validated that the expression levels of TARBP1 was decreased in TARBP1-knockdown prostate cancer cell compared with cells transfected with negative control LV-shNC RNA. The tumor growths were significant smaller in the group B (LNCaP-LV-shTARBP1) compared with group A (LNCaP-LV-shNC). Knocking down TARBP1 significantly suppressed the tumor progression of BALB/C nude xenograft. Moreover, body weight of mice in LNCaP-LV-shNC group increased significant slowly compared with LNCaP-LV-shTARBP1 group. The result of western blot analysis for TARBP1 in tumor tissues from xenograft nude mice bearing orthotopic LNCaP tumors shows that the expression of TARBP1 was also significantly decreased in the LNCaP-LV-shTARBP1 group compared with LNCaP-LV-shNC group (p < 0.05). Conclusion: We revealed that the TARBP1 highly expressed in prostate cancer and its role in promoting tumor growth. TARBP1 could serve as a potential therapeutic target for prostate cancer treatment and it is also a biomarker for tumor diagnosis and prognosis.
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References
1. Culp MB, Soerjomataram I, Efstathiou JA, et al. Recent Global Patterns in Prostate Cancer Incidence and Mortality Rates. Eur Urol. 2020;77:38-52. https://doi.org/10.1016/j.eururo.2019.08.005
2. Bergengren O, Pekala KR, Matsoukas K, et al. 2022 Update on Prostate Cancer Epidemiology and Risk Factors-A Systematic Review. Eur Urol. 2023;84:191-206. https://doi.org/10.1016/j.eururo.2023.04.021
3. Giri VN, Hegarty SE, Hyatt C, et al. Germline genetic testing for inherited prostate cancer in practice: Implications for genetic testing, precision therapy, and cascade testing. Prostate. 2019;79:333-339. https://doi.org/10.1002/pros.23739
4. Pritchard CC, Mateo J, Walsh MF, et al. Inherited DNA-Repair Gene Mutations in Men with Metastatic Prostate Cancer. N Engl J Med. 2016;375:443-453. https://doi.org/10.1056/nejmoa1603144
5. Daniels SM, Gatignol A. The multiple functions of TRBP, at the hub of cell responses to viruses, stress and cancer. Microbiol Mol Biol Rev. 2012;76:652-666. https://doi.org/10.1128/mmbr.00012-12
6. Takahashi T, Zenno S, Ishibashi O, et al. Interactions between the non-seed region of siRNA and RNA-binding RLC/RISC proteins, Ago and TRBP, in mammalian cells. Nucleic Acids Res. 2014;42:5256-5269. https://doi.org/10.1093/nar/gku153
7. Gagnon KT, Li L, Chu Y, et al. RNAi factors are present and active in human cell nuclei. Cell Rep. 2014;6:211-221. https://doi.org/10.1016/j.celrep.2013.12.013
8. Shi X, Zhang Y, Wang Y, et al. The tRNA Gm18 methyltransferase TARBP1 promotes hepatocellular carcinoma progression via metabolic reprogramming of glutamine. Cell Death Differ.
2024;31(9):1219-1234. https://doi.org/10.1038/s41418-024-01323-4
9. Jingmei Ye, Jiani Wang, Li Tan, et al. Expression of protein TARBP1 in human hepatocellular carcinoma and its prognostic significance. Int J Clin Exp Pathol. 2015;8(8):9089-9096
10. Melo SA, Ropero S, Moutinho C, et al. A TARBP2 mutation in human cancer impairs microRNA processing and DICER1 function. Nat Genet. 2009;41:365-370. https://doi.org/10.1038/ng.317
11. Jingmei Ye, Jiani Wang, Nana Zhang, et al. Expression of TARBP1 protein in human non‑small‑cell lung cancer and its prognostic significance. Oncol Lett. 2018;15:7182-7190. https://doi.org/10.3892/ol.2018.8202
12. Prashanth Rawla. Epidemiology of Prostate Cancer. World J Oncol. 2019;10(2):63-89. https://doi.org/10.14740/wjon1191
13. Bostwick DG, Burke HB, Djakiew D, et al. Human prostate cancer risk factors. Cancer. 2004;101(10 Suppl):2371-2490. https://doi.org/10.1002/cncr.20408
14. Dagnelie PC, Schuurman AG, Goldbohm RA, et al. Diet, anthropometric measures and prostate cancer risk: a review of prospective cohort and intervention studies. BJU Int. 2004;93(8):1139-1150. https://doi.org/10.1111/j.1464-410x.2004.04795.x
15. Kolonel LN, Altshuler D, Henderson BE. The multiethnic cohort study: exploring genes, lifestyle and cancer risk. Nat Rev Cancer. 2004;4(7):519-527.
16. Wolk A. Diet, lifestyle and risk of prostate cancer. Acta Oncol. 2005;44(3):277-281. https://doi.
org/10.1080/02841860510029572
17. Wilson KM, Giovannucci EL, Mucci LA. Lifestyle and dietary factors in the prevention of lethal prostate cancer. Asian J Androl. 2012;14(3):365-374. https://doi.org/10.1038/aja.2011.142
18. Markozannes G, Tzoulaki I, Karli D, et al. Diet, body size, physical activity and risk of prostate cancer: An umbrella review of the evidence. Eur J Cancer. 2016;69:61-69. https://doi.org/10.1016/j.ejca.2016.09.026
19. Houlahan KE, Livingstone J, Fox NS, et al.: A polygenic two-hit hypothesis for prostate cancer. J Natl Cancer Inst. 2023;115(4):468-472. https://doi.org/10.1093/jnci/djad001
20. Mucci LA, Hjelmborg JB, Harris JR, et al. Familial Risk and Heritability of Cancer Among Twins in Nordic Countries. JAMA. 2016;315(1):68-76. https://doi.org/10.1001/jama.2015.17703
21. Chi YH, Semmes OJ, Jeang KT. A proteomic study of TARRNA binding protein (TRBP) associated factors. Cell Biosci. 2011;1:9. https://doi.org/10.1186/2045-3701-1-9
22. Sanghvi VR, teel LF. The cellular TAR RNA binding protein, TRBP, promotes HIV-1 replication primarily by inhibiting the activation of double-stranded RNA-dependent kinase PKR. J Virol. 2011;85:12614-12621. https://doi.org/10.1128/jvi.05240-11
23. Sand M, Skrygan M, Georgas D, et al. Expression levels of the microRNA maturing microprocessor complex component DGCR8 and the RNA-induced silencing complex (RISC)
components argonaute-1, argonaute-2, PACT, TARBP1, and TARBP2 in epithelial skin cancer. Mol Carcinog. 2011;51:916-922. https://doi.org/10.1002/mc.20861
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