Cargando…

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

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 disea...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6549932/
https://www.ncbi.nlm.nih.gov/pubmed/31006167
http://dx.doi.org/10.1111/cas.14026
_version_ 1783424094651285504
author 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
author_facet 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
author_sort Kurahashi, Ryoma
collection PubMed
description 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.
format Online
Article
Text
id pubmed-6549932
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-65499322019-06-07 MicroRNA‐204‐5p: A novel candidate urinary biomarker of Xp11.2 translocation renal cell carcinoma 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 Cancer Sci Original Articles 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. John Wiley and Sons Inc. 2019-05-24 2019-06 /pmc/articles/PMC6549932/ /pubmed/31006167 http://dx.doi.org/10.1111/cas.14026 Text en © 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Articles
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
MicroRNA‐204‐5p: A novel candidate urinary biomarker of Xp11.2 translocation renal cell carcinoma
title MicroRNA‐204‐5p: A novel candidate urinary biomarker of Xp11.2 translocation renal cell carcinoma
title_full MicroRNA‐204‐5p: A novel candidate urinary biomarker of Xp11.2 translocation renal cell carcinoma
title_fullStr MicroRNA‐204‐5p: A novel candidate urinary biomarker of Xp11.2 translocation renal cell carcinoma
title_full_unstemmed MicroRNA‐204‐5p: A novel candidate urinary biomarker of Xp11.2 translocation renal cell carcinoma
title_short MicroRNA‐204‐5p: A novel candidate urinary biomarker of Xp11.2 translocation renal cell carcinoma
title_sort microrna‐204‐5p: a novel candidate urinary biomarker of xp11.2 translocation renal cell carcinoma
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6549932/
https://www.ncbi.nlm.nih.gov/pubmed/31006167
http://dx.doi.org/10.1111/cas.14026
work_keys_str_mv AT kurahashiryoma microrna2045panovelcandidateurinarybiomarkerofxp112translocationrenalcellcarcinoma
AT kadomatsutsuyoshi microrna2045panovelcandidateurinarybiomarkerofxp112translocationrenalcellcarcinoma
AT babamasaya microrna2045panovelcandidateurinarybiomarkerofxp112translocationrenalcellcarcinoma
AT harachiaki microrna2045panovelcandidateurinarybiomarkerofxp112translocationrenalcellcarcinoma
AT itohhitoshi microrna2045panovelcandidateurinarybiomarkerofxp112translocationrenalcellcarcinoma
AT miyatakeishi microrna2045panovelcandidateurinarybiomarkerofxp112translocationrenalcellcarcinoma
AT endomotoyoshi microrna2045panovelcandidateurinarybiomarkerofxp112translocationrenalcellcarcinoma
AT morinagajun microrna2045panovelcandidateurinarybiomarkerofxp112translocationrenalcellcarcinoma
AT teradakazutoyo microrna2045panovelcandidateurinarybiomarkerofxp112translocationrenalcellcarcinoma
AT arakikimi microrna2045panovelcandidateurinarybiomarkerofxp112translocationrenalcellcarcinoma
AT etomasatoshi microrna2045panovelcandidateurinarybiomarkerofxp112translocationrenalcellcarcinoma
AT schmidtlauras microrna2045panovelcandidateurinarybiomarkerofxp112translocationrenalcellcarcinoma
AT kambatomomi microrna2045panovelcandidateurinarybiomarkerofxp112translocationrenalcellcarcinoma
AT linehanwmarston microrna2045panovelcandidateurinarybiomarkerofxp112translocationrenalcellcarcinoma
AT oikeyuichi microrna2045panovelcandidateurinarybiomarkerofxp112translocationrenalcellcarcinoma