Renal hücreli karsinomda bir heparanaz varyantı olan T5 oluşumunda miR-6814-5p'nin rolü
Amaç: Bu çalışmanın amacı insan renal hücre karsinomu (RHK) vakalarında insan heparanaz proteininin (HPSE) T5 adlı alternatif varyant proteininin aşırı ekspresyonunun nedeninin miR-6814-5p'nin artmış ekspresyonu olup olmadığını araştırmaktır. Ayrıca RHK vakalarının klinik parametreleri ile T5 ve miR-6814-5p ekspresyon seviyelerinin olası korelasyonu değerlendirilmiştir. Gereç ve Yöntem: T5 ve miR-6814-5p ekspresyon analizi, kullanıma hazır RHK cDNA panelinde qPCR yöntemi ile gerçekleştirildi. Bu panel, 10 evre-1, 5 evre-2, 13 evre-3 ve 11 evre-4 RHK hastalarının tümör dokularından ve 9 sağlıklı bireyden alınan normal böbrek dokularından elde edilen 48 cDNA örneğini içeriyordu. Bulgular: TNM evreleri, Fuhrman nükleer derece ve histolojik tip ile miR-6814-5p ve T5 ifadeleri arasında anlamlı bir ilişki bulunmadı. RHK tümör dokularında miR-6814-5p ekspresyon seviyesi, sağlıklı kontrollerden yaklaşık 8 kat daha yüksek ve T5 ekspresyon seviyesi yaklaşık 5 kat daha yüksekti. MiR-6814-5p ve T5 ekspresyon değişiklikleri, RHK vakalarının nötrofil / lenfosit oranı ile istatistiksel olarak anlamlı korelasyon gösterdi. Sonuç: MiR-6814-5p, RHK'de T5 oluşum mekanizmasında rol oynayabilir.
Role of miR-6814-5p for the formation of T5, a heparanase variant, in renal cell carcinoma
Purpose: The aim of this study is to investigate whether the overexpression of human heparanase protein (HPSE) alternative variant protein called T5 is caused by increased expression of miR-6814-5p in human renal cell carcinoma (RCC) cases. In addition, the possible correlation between the clinical parameters of RCC cases and the expression levels of T5 and miR-6814-5p was evaluated. Materials and Methods: T5 and miR-6814-5p expression analysis was performed on ready-to-use RCC cDNA panel by qPCR method. This panel included 48 cDNA samples obtained from tumor tissues of 10 stage-1, 5 stage-2, 13 stage-3 and 11 stage-4 RCC patients and normal kidney tissues from 9 healthy individuals. Results: There was no significant correlation between TNM stages, Fuhrman nuclear grade and histological type and miR-6814-5p and T5 expressions. The expression level of miR-6814-5p in RCC tumor tissues was about 8-fold higher and the T5 expression level about 5-fold higher than healthy controls. MiR-6814-5p and T5 expression changes were statistically significantly correlated with neutrophil/lymphocyte ratio of RCC cases. Conclusion: MiR-6814-5p may play a role in the formation mechanism of T5 in RCC.
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- 1. Cooper TA, Wan L, Dreyfuss G. RNA and disease. Cell. 2009;136:777–93.
- 2. Barash U, Cohen V, Arvatz G, Gingis S, Levy F. A novel human heparanase splice variant, T5, endowed with protumorigenic characteristics. FASEB J. 2010;24:1239–48.
- 3. Von M, Bernhart SH, Pansky A, Richter C, Kohl T, Deckert M et al. Beyond the 3′ UTR binding– microRNA-induced protein truncation via DNA binding. Oncotarget. 2018;9:32855.
- 4. Saydam F, Değirmenci İ, Güneş HV. MicroRNAs and cancer. Dicle Med J. 2011;38:113-20.
- 5. Ergün, S. In silico analysis of biomarker potentials of miRNA-mediated ceRNAs in prostate cancer. Dicle Med J. 2018;45:415-429.
- 6. Wong N, Wang X. miRDB: an online resource for microRNA target prediction and functional annotations. Nucleic Acids Res. 2014;43:D146-52.
- 7. Rennie W, Liu C, Carmack, CS, Wolenc A, Kanoria S, Lu J et al. STarMir: a web server for prediction of microRNA binding sites. Nucleic Acids Res. 2014;42:W114-8.
- 8. Yang SF, Hsu HL, Chao TK, Hsiao CJ, Lin YF, Cheng CW. Annexin A2 in renal cell carcinoma: expression, function, and prognostic significance. Urol Oncol. 2015;33:22-e11.
- 9. Ergün S, Altay DU, Güneş S, Büyükalpelli R, Karahan SC, Tomak L et al. Tr-KIT/c-KIT ratio in renal cell carcinoma. Mol Biol Rep. 2019;46:5287-94.
- 10. Akgun S, Kucuksayan H, Tokgun O, Karagur ER, Can O, Akca H. miR-548a-3p, miR-548as-3p and miR-8078 are responsible for NSCLC. September 2016. 2016: 41th FEBS Congress, Ephesus/Kuşadası, TurkeyAt: Ephesus/Kuşadası, Turkey, Volume: 283.
- 11. Yonemori K, Seki N, Idichi T, Kurahara H, Osako Y, Koshizuka K et al. The microRNA expression signature of pancreatic ductal adenocarcinoma by RNA sequencing: anti-tumour functions of the microRNA-216 cluster. Oncotarget. 2017;8:70097.
- 12. Shuai L, Zifan H, Ziwei L, Chengwu Z, Lijian Y, Shaohua C et al. SNPs/mutations in BCL11B-3'UTR miRNA binding site of healthy humans and T-ALL patients. Chinese J Pathophysiology. 2018;07:1228- 1231.
- 13. Sharma B, Randhawa V, Vaiphei K, Gupta V, Dahiya D, Agnihotri N. Expression of miR-18a-5p, miR-144- 3p, and miR-663b in colorectal cancer and their association with cholesterol homeostasis. J Steroid Biochem. 2021;208:105822.
- 14. Ye Z, Sun B, Xiao Z. Machine learning identifies 10 feature miRNAs for lung squamous cell carcinoma. Gene. 2020;749:144669.
- 15. Hu K, Lou L, Ye J, Zhang S. Prognostic role of the neutrophil–lymphocyte ratio in renal cell carcinoma: a meta-analysis. BMJ Open. 2015;5:e006404.
- 16. Chen P, Zhang Z, Chen X. Overexpression of PKMYT1 facilitates tumor development and is correlated with poor prognosis in clear cell renal cell carcinoma. Med Sci Monit. 2020; 6:e926755-1.