ABSTRACT
BACKGROUND: Renal cell carcinoma is difficult to diagnose and unpredictable in disease course and severity. There are no specific biomarkers for diagnosis and prognosis estimation feasible in clinical practice. Long non-coding RNAs (lncRNAs) have emerged as potent regulators of gene expression in recent years. Aside from their cellular role, their expression patterns could be used as a biomarker of ongoing pathology. METHODS: In this work, we used next-generation sequencing for global lncRNA expression profiling in tumor and non-tumor tissue of RCC patients. The four candidate lncRNAs have been further validated on an independent cohort. PVT1, as the most promising lncRNA, has also been studied using functional in vitro tests. RESULTS: Next-generation sequencing showed significant dysregulation of 1163 lncRNAs; among them top 20 dysregulated lncRNAs were AC061975.7, AC124017.1, AP000696.1, AC148477.4, LINC02437, GATA3-AS, LINC01762, LINC01230, LINC01271, LINC01187, LINC00472, AC007849.1, LINC00982, LINC01543, AL031710.1, and AC019197.1 as down-regulated lncRNAs; and SLC16A1-AS1, PVT1, LINC0887, and LUCAT1 as up-regulated lncRNAs. We observed statistically significant dysregulation of PVT1, LUCAT1, and LINC00982. Moreover, we studied the effect of artificial PVT1 decrease in renal cell line 786-0 and observed an effect on cell viability and migration. CONCLUSION: Our results show not only the diagnostic but also the therapeutic potential of PVT1 in renal cell carcinoma.
Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , RNA, Long Noncoding , Biomarkers, Tumor/genetics , Biomarkers, Tumor/physiology , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/physiopathology , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Cell Survival/genetics , Gene Expression Regulation, Neoplastic , High-Throughput Nucleotide Sequencing , Humans , Kidney Neoplasms/genetics , Kidney Neoplasms/physiopathology , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , RNA, Long Noncoding/physiologyABSTRACT
LncRNA PVT1 (plasmacytoma variant translocation 1) has become a staple of the lncRNA profile in patients with renal cell carcinoma (RCC). Common dysregulation in renal tumors outlines the essential role of PVT1 in the development of RCC. There is already a plethora of publications trying to uncover the cellular mechanisms of PVT1-mediated regulation and its potential exploitation in management of RCC. In this review, we summarize the literature focused on PVT1 in RCC and aim to synthesize the current knowledge on its role in the cells of the kidney. Further, we provide an overview of the lncRNA profiling studies that have identified a more or less significant association of PVT1 with the clinical behavior of RCC. Based on our search, we analyzed the 17 scientific papers discussed in this review that provide robust support for the indispensable role of PVT1 in RCC development and future personalized therapy.
Subject(s)
Carcinoma, Renal Cell/genetics , Kidney Neoplasms/genetics , RNA, Long Noncoding/genetics , Cell Movement , Cell Proliferation , Gene Expression Regulation, Neoplastic , Humans , Prognosis , Up-RegulationABSTRACT
BACKGROUND: A modern approach to identify biomarkers of solid cancers in tissues and body fluids is based on microRNA (miRNA) expression profiling. miRNAs are a group of approximately 3.000 short noncoding RNAs containing 18-25 nucleotides that regulate gene expression at the post-transcriptional (mRNA) level. The abilities of miRNAs to inhibit the translation or induce degradation of oncogenes and tumor suppressors indicate that they are involved in carcinogenesis. There is increasing evidence that miRNAs regulate apoptosis, cell proliferation, differentiation, and invasion. miRNA expression profiles are therefore often analyzed for molecular diagnostics of solid cancers, similar to analyses based on mRNA profiling. It is important that miRNAs are highly stable and present at high levels in body fluids, including saliva, for analytic usage. miRNAs in saliva have been successfully tested as potential diagnostic biomarkers of many solid cancers. The main advantage of these miRNAs is that saliva samples can be collected non-invasively. AIM: This review aims to summarize current knowledge of circulating miRNAs in solid cancers, with a focus on the use of miRNAs in saliva for oncology diagnostics. Key words: microRNA - saliva - diagnosis - cancer The results of this research have been acquired within CEITEC 2020 (LQ1601) project with fi nancial contribution made by the Ministry of Education, Youths and Sports of the Czech Republic within special support paid from the National Programme for Sustainability II funds. The authors declare they have no potential confl icts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 8. 3. 2018 Accepted: 15. 5. 2018.
