Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 May-Jun;18(3):253-259.
doi: 10.21873/cgp.20256.

Profiling of Serum Extracellular Vesicles Reveals miRNA-4525 as a Potential Biomarker for Advanced Renal Cell Carcinoma

Yuka Muramatsu-Maekawa  1 , Kyojiro Kawakami  2 , Yasunori Fujita  3 , Manabu Takai  1 , Daiki Kato  1 , Keita Nakane  1 , Taku Kato  4 , Tomohiro Tsuchiya  1 , Takuya Koie  1 , Yuri Miura  2 , Masafumi Ito  5 , Kosuke Mizutani  6   7
Affiliations
Free PMC article

Profiling of Serum Extracellular Vesicles Reveals miRNA-4525 as a Potential Biomarker for Advanced Renal Cell Carcinoma

Yuka Muramatsu-Maekawa et al. Cancer Genomics Proteomics. 2021 May-Jun.
Free PMC article

Abstract

Aim: To identify novel diagnostic markers for renal cell carcinoma (RCC), we analyzed miRNAs in serum extracellular vesicles (EVs).

Materials and methods: EVs were purified from serum of healthy controls and patients with localized and advanced RCC using T-cell immunoglobulin domain and mucin domain-containing protein 4 conjugated to magnetic beads. miRNA profiling of EVs was conducted by microarray analysis. miRNA expression was examined by quantitative reverse transcription-polymerase chain reaction. Lastly, proteomic analysis of RCC cells transfected with a miRNA inhibitor was performed to identify its potential targets.

Results: Microarray analysis revealed that nine miRNAs were increased by more than 1.5-fold in EVs from patients with RCC. Among them, miRNA-4525 was significantly elevated; miRNA-4525 expression was higher in RCC tissue than in the adjacent normal tissue. Proteomic analysis identified alpha fetoprotein and albumin as its potential targets.

Conclusion: These findings suggest the potential of miRNA-4525 in serum EVs as a novel biomarker for advanced RCC.

Keywords: Renal cell carcinoma; extracellular vesicle; microarray analysis; mirna-4525; proteomic analysis.

PubMed Disclaimer

Conflict of interest statement

The Authors declare that they have no conflicts of interest in regard to this study.

Figures

Figure 1
Figure 1. Confirmation of isolation of extracellular vesicles (EVs) from serum. EVs were isolated by using T-cell immunoglobulin domain and mucin domain-containing protein 4/human Fc chimera recombinant protein-conjugated magnetic beads from pooled serum of healthy controls, and patients with localized or advanced renal cell carcinoma (n=4 in each group).
Figure 2
Figure 2. Expression levels of miRNA-4525 and miRNA-4534 in extracellular vesicles (EVs) isolated from patients with renal cell carcinoma (RCC). miRNA-4525 expression in serum EVs significantly was increased in patients with advanced RCC compared with healthy controls, whereas miRNA-4534 expression was not. Cel-miR-39-3p was used as spike-in control for standardization. Bars and lines represent the median and 95% confidence interval, respectively.
Figure 3
Figure 3. miRNA-4525 expression in renal cell carcinoma (RCC) tissue. miRNA-4525 expression was significantly increased in RCC tissue compared to that in adjacent normal tissue. Cel-miR-39-3p was used as spike-in control for standardization.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Rini BI, Escudier B, Tomczak P, Kaprin A, Szczylik C, Hutson TE, Michaelson MD, Gorbunova VA, Gore ME, Rusakov IG, Negrier S, Ou YC, Castellano D, Lim HY, Uemura H, Tarazi J, Cella D, Chen C, Rosbrook B, Kim S, Motzer RJ. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): A randomised phase 3 trial. Lancet. 2011;378(9807):1931–1939. doi: 10.1016/S0140-6736(11)61613-9. - DOI - PubMed
    1. Motzer RJ, Tannir NM, McDermott DF, Arén Frontera O, Melichar B, Choueiri TK, Plimack ER, Barthélémy P, Porta C, George S, Powles T, Donskov F, Neiman V, Kollmannsberger CK, Salman P, Gurney H, Hawkins R, Ravaud A, Grimm MO, Bracarda S, Barrios CH, Tomita Y, Castellano D, Rini BI, Chen AC, Mekan S, McHenry MB, Wind-Rotolo M, Doan J, Sharma P, Hammers HJ, Escudier B, CheckMate 214 Investigators. Nivolumab plus Ipilimumab versus Sunitinib in advanced renal-cell carcinoma. N Engl J Med. 2018;378(14):1277–1290. doi: 10.1056/NEJMoa1712126. - DOI - PMC - PubMed
    1. Rini BI, Plimack ER, Stus V, Gafanov R, Hawkins R, Nosov D, Pouliot F, Alekseev B, Soulières D, Melichar B, Vynnychenko I, Kryzhanivska A, Bondarenko I, Azevedo SJ, Borchiellini D, Szczylik C, Markus M, McDermott RS, Bedke J, Tartas S, Chang YH, Tamada S, Shou Q, Perini RF, Chen M, Atkins MB, Powles T, KEYNOTE-426 Investigators Pembrolizumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma. N Engl J Med. 2019;380(12):1116–1127. doi: 10.1056/NEJMoa1816714. - DOI - PubMed
    1. Murakami Y, Toyoda H, Tanahashi T, Tanaka J, Kumada T, Yoshioka Y, Kosaka N, Ochiya T, Taguchi YH. Comprehensive miRNA expression analysis in peripheral blood can diagnose liver disease. PLoS One. 2012;7(10):e48366. doi: 10.1371/journal.pone.0048366. - DOI - PMC - PubMed
    1. Zhong S, Golpon H, Zardo P, Borlak J. miRNAs in lung cancer. A systematic review identifies predictive and prognostic miRNA candidates for precision medicine in lung cancer. Transl. 2020;Res:S1931. doi: 10.1016/j.trsl.2020.11.012. - DOI - PubMed