EXPRESSION OF miRNA AS PROGNOSTIC MARKERS OF RENAL CELL CARCINOMA COURSE
DOI:
https://doi.org/10.32471/exp-oncology.2312-8852.vol-44-no-2.17883Keywords:
miRNA, prognosis, real-time PCR, renal cell carcinomaAbstract
Renal cell carcinoma (RCC) is one of the most common solid tumors in adults. There is a lack of reliable prognostic and predictive biomarkers for RCC course. Dysregulation of miRNAs expression has been reported to be involved in RCC progression. However, the data on miRNAs expression patterns in tumors are controversial. Aim: To investigate the expression and clinical significance of miR-99b, -144, -155, -210, -222, -302а, -377 in RCC ex vivo. Materials and Methods: Retrospective analysis of the expression levels of miRNAs -99b, -144, -155, -210, -222, -302а, -377 in tumor tissue of 126 patients with clear cell RCC was performed using quantitative polymerase chain reaction. Results: Overexpression of miR-99b, -222, -302a and low levels of miR-155 in RCC tissues were significantly associated with advanced tumor stage (p < 0.05). In majority of patients with distant metastases (> 60%), high levels of miR-99b and 377 were detected (p < 0.05). High/low miR-99b, -144, -155, -210, -222, and -302a ratio was significantly associated with Fuhrman grade of tumors. Conclusion: Aberrant expression of miR-99b, -144, -155, -210, -222, -302а, -377 is strongly associated with advanced RCC, and panel of these miRNAs may be a useful prognostic marker for RCC course.
References
Cancer in Ukraine, 2019–2020. Incidence, mortality, activities of oncological service. Bull Nat Cancer Registry Ukr, No. 22, Кyiv, 2020. 82 p.
Li M, Wang Y, Song Y, et al. MicroRNAs in renal cell carcinoma: a systematic review of clinical implications. Oncol Rep 2015; 33: 1571–8. https://doi.org/10.3892/or.2015.3799
Bullock A, McDermott DF, Atkins MB. Management of metastatic renal cell carcinoma in patients with poor prognosis. Cancer Manag Res 2010; 2: 123–32.
Croce CM. Causes and consequences of miRNA dysregulation in cancer. Nat Rev Genet 2009; 10: 704–14. https://doi.org/10.1038/nrg2634
Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 1993; 75: 843–54. https://doi.org/10.1016/0092-8674(93)90529-Y
TNM Classification of Malignant Tumours, 8th Edition. Brierley JD, Gospodarowicz MK, Wittekind Ch, Eds. New York: Wiley-Blackwell, 2017. 272 p.
Moch H, Cubilla AL, Humphrey PA, et al. The 2016 WHO classification of tumours of the urinary system and male genital organs-part a: renal, penile, and testicular tumours. Eur Urol 2016; 70: 93. https://doi.org/10.1016/j.eururo.2016.02.029
Kutikov A, Uzzo RG. The R.E.N.A.L. nephrometry score: a comprehensive standardized system for quantitating renal tumor size, location and depth. J Urol 2009; 182: 844–53. https://doi.org/10.1016/j.juro.2009.05.035
Voylenko OA, Stakhovsky OE, Vitruk IV, et al. Efficacy of neoadjuvant targeted therapy in treatment of patients with localized clear-cell renal cell carcinoma. Adv Urol 2021: 6674637. https://doi.org/10.1155/2021/6674637
Ukrainian guidelines on renal cell carcinoma 2022 (in Ukrainian). Accessed from https://www.dec.gov.ua/mtd/rak-nyrky
Vitruk YuV, Semko SL, Voylenko OA, et al. Evaluation of response to tyrosine kinase inhibitors in renal cell carcinoma patients based on expression of miR-99b, -144, -210, -222, -302а and -377 in tumor tissue. Exp Oncol 2021; 43: 98–103. https://doi.org/10.32471/exp-oncology.2312-8852.vol-43-no-2.16383
Castelluzzo M, Perinelli A, Detassis S, et al. MiRNA-QC-and-Diagnosis: An R package for diagnosis based on miRNA expression. SoftwareX 2020; 12: 100569. https://doi.org/10.1016/j.softx.2020.100569
Lin T, Yang Y, Ye X, et al. Low expression of miR-99b promotes progression of clear cell renal cell carcinoma by up-regulating IGF1R/Akt/mTOR signaling. Int J Clin Exp Pathol 2020; 13: 3083–91.
Xiao W, Lou N, Ruan H, et al. Mir-144-3p promotes cell proliferation, metastasis, sunitinib resistance in clear cell renal cell carcinoma by downregulating ARID1A. Cell Physiol Biochem 2017: 43: 2420–33. https://doi.org/10.1159/000484395
Yamada Y, Arai T, Kojima S, et al. Regulation of antitumor miR-144-5p targets oncogenes: direct regulation of syndecan-3 and its clinical significance. Cancer Sci 2018; 109: 2919–36. https://doi.org/10.1111/cas.13722
Kooshkaki O, Rezaei Z, Rahmati M, et al. MiR-144: A new possible therapeutic target and diagnostic/prognostic tool in cancers. Int J Mol Sci 2020; 21: 2578. https://doi.org/10.3390/ijms21072578
Zhang J, Ye Y, Chang DW, et al. Global and targeted miRNA expression profiling in clear cell renal cell carcinoma tissues potentially links miR-155-5p and miR-210-3p to both tumorigenesis and recurrence. Am J Pathol 2018; 188: 2487–96. https://doi.org/10.1016/j.ajpath.2018.07.026
Gao Y, Ma X, Yao Y, et al. miR-155 regulates the proliferation and invasion of clear cell renal cell carcinoma cells by targeting E2F2. Oncotarget 2016; 7: 20324. https://doi.org/10.18632/oncotarget.7951
Neal CS, Michael MZ, Rawlings LH, et al. The VHL-dependent regulation of microRNAs in renal cancer. BMC Med 2010; 8: 1–17. https://doi.org/10.1186/1741-7015-8-64
Lyu J, Zhu Y, Zhang Q. An increased level of MiR-222-3p is associated with TMP2 suppression, ERK activation and is associated with metastasis and a poor prognosis in renal clear cell carcinoma. Cancer Biomark 2020; 28: 141–9. https://doi.org/10.3233/CBM-190264
Zhao X, Wang P, Liu J, et al. Gas5 exerts tumor-suppressive functions in human glioma cells by targeting miR-222. Mol Ther 2015; 23: 1899–911. https://doi.org/10.1038/mt.2015.170
Rosa A, Brivanlou AH. A regulatory circuitry comprised of miR-302 and the transcription factors OCT4 and NR2F2 regulates human embryonic stem cell differentiation. EMBO J 2011; 30: 237–48. https://doi.org/10.1038/emboj.2010.319
Gu DH, Mao JH, Pan XD, et al. microRNA-302c-3p inhibits renal cell carcinoma cell proliferation by targeting Grb2-associated binding 2 (Gab2). Oncotarget 2017; 8: 26334. https://doi.org/10.18632/oncotarget.15463
Wang R, Ma Y, Yu D, et al. miR-377 functions as a tumor suppressor in human clear cell renal cell carcinoma by targeting ETS1. Biomed Pharmacother 2015; 70: 64–71. https://doi.org/10.1016/j.biopha.2015.01.012
Huang Z, Ding Y, Zhang L, et al. Upregulated circPDK1 promotes RCC cell migration and invasion by regulating the miR-377-3P-NOTCH1 axis in renal cell carcinoma. Onco Targets Ther 2020; 13: 11237. https://doi.org/10.2147/OTT.S280434
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