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Long Non-Coding PROX1-AS1 Expression Correlates with Renal Cell Carcinoma Metastasis and Aggressiveness

1
Institute of Molecular Medicine, Sechenov First Moscow State Medical University, 119991 Moscow, Russia
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Department of Biomedicine and Genetics, Medical University of Lodz, 90-419 Lodz, Poland
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Laboratory of Epigenetics, Research Centre for Medical Genetics, Moskvorechye str. 1, 115478 Moscow, Russia
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Institute for Urology and Reproductive Health, Sechenov University, 119992 Moscow, Russia
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Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, Russia
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Department of Biotechnology, Sirius University of Science and Technology, 1 Olympic Ave, 354340 Sochi, Russia
*
Authors to whom correspondence should be addressed.
Academic Editor: Giulia Fontemaggi
Non-Coding RNA 2021, 7(2), 25; https://doi.org/10.3390/ncrna7020025
Received: 10 December 2020 / Revised: 2 April 2021 / Accepted: 8 April 2021 / Published: 10 April 2021
(This article belongs to the Special Issue Non-Coding RNA and Tumor Cell Motility)
Long non-coding RNAs (lncRNAs) can be specifically expressed in different tissues and cancers. By controlling the gene expression at the transcriptional and translational levels, lncRNAs have been reported to be involved in tumor growth and metastasis. Recent data demonstrated that multiple lncRNAs have a crucial role in renal cell carcinoma (RCC) progression—the most common malignant urogenital tumor. In the present study, we found a trend towards increased PROX1 antisense RNA 1 (PROX1-AS1) expression in RCC specimens compared to non-tumoral margins. Next, we found a positive correlation between PROX1-AS1 expression and the occurrence of distant and lymph node metastasis, higher tumor stage (pT1 vs. pT2 vs. pT3–T4) and high-grade (G1/G2 vs. G3/G4) clear RCC. Furthermore, global demethylation in RCC-derived cell lines (769-P and A498) and human embryonic kidney 293 (HEK293) cells induced a significant increase of PROX1-AS1 expression level, with the most remarkable change in HEK293 cells. In line with this evidence, bisulfite sequencing analysis confirmed the specific demethylation of bioinformatically selected CpG islands on the PROX1-AS1 promoter sequence in the HEK293 cell line but not in the tumor cells. Additionally, the human specimen analysis showed the hemimethylated state of CG dinucleotides in non-tumor kidney tissues, whereas the tumor samples presented the complete, partial, or no demethylation of CpG-islands. In conclusion, our study indicated that PROX1-AS1 could be associated with RCC progression, and further investigations may define its role as a new diagnostic marker and therapeutic target. View Full-Text
Keywords: non-coding RNA; PROX1-AS1; renal cell carcinoma; human specimens non-coding RNA; PROX1-AS1; renal cell carcinoma; human specimens
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MDPI and ACS Style

Rudzinska, M.; Czarnecka-Chrebelska, K.H.; Kuznetsova, E.B.; Maryanchik, S.V.; Parodi, A.; Korolev, D.O.; Potoldykova, N.; Svetikova, Y.; Vinarov, A.Z.; Nemtsova, M.V.; Zamyatnin, A.A., Jr. Long Non-Coding PROX1-AS1 Expression Correlates with Renal Cell Carcinoma Metastasis and Aggressiveness. Non-Coding RNA 2021, 7, 25. https://doi.org/10.3390/ncrna7020025

AMA Style

Rudzinska M, Czarnecka-Chrebelska KH, Kuznetsova EB, Maryanchik SV, Parodi A, Korolev DO, Potoldykova N, Svetikova Y, Vinarov AZ, Nemtsova MV, Zamyatnin AA Jr.. Long Non-Coding PROX1-AS1 Expression Correlates with Renal Cell Carcinoma Metastasis and Aggressiveness. Non-Coding RNA. 2021; 7(2):25. https://doi.org/10.3390/ncrna7020025

Chicago/Turabian Style

Rudzinska, Magdalena; Czarnecka-Chrebelska, Karolina H.; Kuznetsova, Ekaterina B.; Maryanchik, Sofya V.; Parodi, Alessandro; Korolev, Dmitry O.; Potoldykova, Nataliya; Svetikova, Yulia; Vinarov, Andrey Z.; Nemtsova, Marina V.; Zamyatnin, Andrey A., Jr. 2021. "Long Non-Coding PROX1-AS1 Expression Correlates with Renal Cell Carcinoma Metastasis and Aggressiveness" Non-Coding RNA 7, no. 2: 25. https://doi.org/10.3390/ncrna7020025

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