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.

Anahtar Kelimeler:

Renal hücreli karsinom, heparanaz, gen ifade düzenlenmesi, miR-6814-5p

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.

Keywords:

Renal cell carcinoma, heparanase, gene expression regulation, miR-6814-5p,

PDF

___

1) Cooper TA, Wan L, Dreyfuss G. RNA and disease. Cell. 2009; 136: 777–793.
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: 1239–1248.
3) Von M, Bernhart SH, Pansky A, Richter C, Kohl T, Deckert M, Fries JW. Beyond the 3′ UTR binding–microRNA-induced protein truncation via DNA binding. Oncotarget. 2018; 9(67): 32855.
4) Saydam F, Değirmenci İ, Güneş HV. MicroRNAs and cancer. Dicle Med J. 2011; 38 (1): 113-120.
5) Ergün, S. In silico analysis of biomarker potentials of miRNA-mediated ceRNAs in prostate cancer. Dicle Med J. 2018; 45(4): 415-429.
6) Wong N, Wang X. miRDB: an online resource for microRNA target prediction and functional annotations. Nucleic Acids Res. 2014; 43: D146-D152.
7) Rennie W, Liu C, Carmack, CS, Wolenc A, Kanoria S, Lu J, Ding Y. STarMir: a web server for prediction of microRNA binding sites. Nucleic Acids Res. 2014; 42: W114-W118.
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 Semin Ori. 2015; 33(1), 22-e11.
9) Ergün S, Altay DU, Güneş S, Büyükalpelli R, Karahan SC, Tomak L, Abur Ü. Tr-KIT/c-KIT ratio in renal cell carcinoma. Mol Biol Rep. 2019; 46(5): 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. 2016 Wiley-Blackwell.
11) Yonemori K, Seki N, Idichi T, Kurahara H, Osako Y, Koshizuka K, Natsugoe S. The microRNA expression signature of pancreatic ductal adenocarcinoma by RNA sequencing: anti-tumour functions of the microRNA-216 cluster. Oncotarget. 2017; 8(41): 70097.
12) Shuai L, Zifan H, Ziwei L, Chengwu Z, Lijian Y, Shaohua C, Yangqiu L. 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(4): e006404.