Open AccessMicroRNA‐204‐5p: A novel candidate urinary biomarker of Xp11.2 translocation renal cell carcinoma
Author(s) -
Kurahashi Ryoma,
Kadomatsu Tsuyoshi,
Baba Masaya,
Hara Chiaki,
Itoh Hitoshi,
Miyata Keishi,
Endo Motoyoshi,
Morinaga Jun,
Terada Kazutoyo,
Araki Kimi,
Eto Masatoshi,
Schmidt Laura S.,
Kamba Tomomi,
Linehan W. Marston,
Oike Yuichi
Publication year - 2019
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.14026
Subject(s) - cancer research , renal cell carcinoma , fusion gene , microrna , microvesicles , biology , kidney , pathology , medicine , gene , endocrinology , genetics
Xp11.2 translocation renal cell carcinoma (Xp11 tRCC ) is a rare sporadic pediatric kidney cancer caused by constitutively active TFE 3 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 ‐ TFE 3 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 ‐ TFE 3 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 TFE 3 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 ‐ TFE 3 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 .