MicroRNA-204-5p: A novel candidate urinary biomarker of Xp11.2 translocation renal cell carcinoma

Ryoma Kurahashi, Tsuyoshi Kadomatsu, Masaya Baba, Chiaki Hara, Hitoshi Itoh, Keishi Miyata, Motoyoshi Endo, Jun Morinaga, Kazutoyo Terada, Kimi Araki, Masatoshi Eto, Laura S. Schmidt, Tomomi Kamba, W. Marston Linehan, Yuichi Oike

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3 Citations (Scopus)

Abstract

Xp11.2 translocation renal cell carcinoma (Xp11 tRCC) is a rare sporadic pediatric kidney cancer caused by constitutively active TFE3 fusion proteins. Tumors in patients with Xp11 tRCC tend to recur and undergo frequent metastasis, in part due to lack of methods available to detect early-stage disease. Here we generated transgenic (Tg) mice overexpressing the human PRCC-TFE3 fusion gene in renal tubular epithelial cells, as an Xp11 tRCC mouse model. At 20 weeks of age, mice showed no histological abnormalities in kidney but by 40 weeks showed Xp11 tRCC development and related morphological and histological changes. MicroRNA (miR)-204-5p levels in urinary exosomes of 40-week-old Tg mice showing tRCC were significantly elevated compared with levels in control mice. MicroRNA-204-5p expression also significantly increased in primary renal cell carcinoma cell lines established both from Tg mouse tumors and from tumor tissue from 2 Xp11 tRCC patients. All of these lines secreted miR-204-5p-containing exosomes. Notably, we also observed increased miR-204-5p levels in urinary exosomes in 20-week-old renal PRCC-TFE3 Tg mice prior to tRCC development, and those levels were equivalent to those in 40-week-old Tg mice, suggesting that miR-204-5p increases follow expression of constitutively active TFE3 fusion proteins in renal tubular epithelial cells prior to overt tRCC development. Finally, we confirmed that miR-204-5p expression significantly increases in noncancerous human kidney cells after overexpression of a PRCC-TFE3 fusion gene. These findings suggest that miR-204-5p in urinary exosomes could be a useful biomarker for early diagnosis of patients with Xp11 tRCC.

Original languageEnglish
Pages (from-to)1897-1908
Number of pages12
JournalCancer Science
Volume110
Issue number6
DOIs
Publication statusPublished - Jun 2019

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All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Kurahashi, R., Kadomatsu, T., Baba, M., Hara, C., Itoh, H., Miyata, K., ... Oike, Y. (2019). MicroRNA-204-5p: A novel candidate urinary biomarker of Xp11.2 translocation renal cell carcinoma. Cancer Science, 110(6), 1897-1908. https://doi.org/10.1111/cas.14026