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NACC1, as a Target of MicroRNA-331-3p, Regulates Cell Proliferation in Urothelial Carcinoma Cells

The nucleus accumbens-associated protein 1 (NACC1) is a transcription factor constitutively expressed in the urothelium, where it regulates cell growth, senescence, autophagy, and epithelial-mesenchymal transition. microRNA (miRNA) constitutes a class of small non-coding RNAs which are involved in c...

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Autores principales: Morita, Kohei, Fujii, Tomomi, Itami, Hiroe, Uchiyama, Tomoko, Nakai, Tokiko, Hatakeyama, Kinta, Sugimoto, Aya, Miyake, Makito, Nakai, Yasushi, Tanaka, Nobumichi, Shimada, Keiji, Yamazaki, Masaharu, Fujimoto, Kiyohide, Ohbayashi, Chiho
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6210667/
https://www.ncbi.nlm.nih.gov/pubmed/30248959
http://dx.doi.org/10.3390/cancers10100347
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author Morita, Kohei
Fujii, Tomomi
Itami, Hiroe
Uchiyama, Tomoko
Nakai, Tokiko
Hatakeyama, Kinta
Sugimoto, Aya
Miyake, Makito
Nakai, Yasushi
Tanaka, Nobumichi
Shimada, Keiji
Yamazaki, Masaharu
Fujimoto, Kiyohide
Ohbayashi, Chiho
author_facet Morita, Kohei
Fujii, Tomomi
Itami, Hiroe
Uchiyama, Tomoko
Nakai, Tokiko
Hatakeyama, Kinta
Sugimoto, Aya
Miyake, Makito
Nakai, Yasushi
Tanaka, Nobumichi
Shimada, Keiji
Yamazaki, Masaharu
Fujimoto, Kiyohide
Ohbayashi, Chiho
author_sort Morita, Kohei
collection PubMed
description The nucleus accumbens-associated protein 1 (NACC1) is a transcription factor constitutively expressed in the urothelium, where it regulates cell growth, senescence, autophagy, and epithelial-mesenchymal transition. microRNA (miRNA) constitutes a class of small non-coding RNAs which are involved in cell proliferation, differentiation, and progression of tumors. miRNAs and their target molecules are utilized for molecular diagnosis of urothelial carcinoma. NACC1 is one of several putative target molecules of miR-331-3p, and is associated with cell proliferation in cancers such as prostate and cervical cancer. Functional experiments involving miR-331-3p and its target molecule NACC1 were conducted using the urothelial carcinoma (UC) cell lines, T24, UMUC6, and KU7. Furthermore, quantitative reverse transcription polymerase chain reaction and immunostaining were performed to evaluate the expression of NACC1 in UC derived from transurethral resection of bladder tumor (TUR-Bt) specimens. The methane thiosulfonate (MTS) assay revealed that cell proliferation was significantly reduced after transient transfection of miR-331-3p precursor and/or NACC1 siRNA in UC cells. Cell senescence via cell cycle arrest at the G1 phase was induced by NACC1 inhibition. On the other hand, suppression of NACC1 induced cell migration and invasion abilities. Immunohistochemical analysis of TUR-Bt specimens revealed that over 70% of UC cells presented strongly positive results for NACC1. In contrast, normal urothelial cells were weakly positive for NACC1. It was also found that NACC1 expression was lower in invasive UC cells than in non-invasive UC cells. Loss of NACC1 induced vessel invasion in invasive UC tissues. The present results indicate that NACC1 regulated by miR-331-3p contributes to cell proliferation, and is involved in cell migration and invasion. This suggests that NACC1 can serve as a potential target molecule for the prediction and prognosis of UC, and can contribute to effective treatment strategies.
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spelling pubmed-62106672018-11-02 NACC1, as a Target of MicroRNA-331-3p, Regulates Cell Proliferation in Urothelial Carcinoma Cells Morita, Kohei Fujii, Tomomi Itami, Hiroe Uchiyama, Tomoko Nakai, Tokiko Hatakeyama, Kinta Sugimoto, Aya Miyake, Makito Nakai, Yasushi Tanaka, Nobumichi Shimada, Keiji Yamazaki, Masaharu Fujimoto, Kiyohide Ohbayashi, Chiho Cancers (Basel) Article The nucleus accumbens-associated protein 1 (NACC1) is a transcription factor constitutively expressed in the urothelium, where it regulates cell growth, senescence, autophagy, and epithelial-mesenchymal transition. microRNA (miRNA) constitutes a class of small non-coding RNAs which are involved in cell proliferation, differentiation, and progression of tumors. miRNAs and their target molecules are utilized for molecular diagnosis of urothelial carcinoma. NACC1 is one of several putative target molecules of miR-331-3p, and is associated with cell proliferation in cancers such as prostate and cervical cancer. Functional experiments involving miR-331-3p and its target molecule NACC1 were conducted using the urothelial carcinoma (UC) cell lines, T24, UMUC6, and KU7. Furthermore, quantitative reverse transcription polymerase chain reaction and immunostaining were performed to evaluate the expression of NACC1 in UC derived from transurethral resection of bladder tumor (TUR-Bt) specimens. The methane thiosulfonate (MTS) assay revealed that cell proliferation was significantly reduced after transient transfection of miR-331-3p precursor and/or NACC1 siRNA in UC cells. Cell senescence via cell cycle arrest at the G1 phase was induced by NACC1 inhibition. On the other hand, suppression of NACC1 induced cell migration and invasion abilities. Immunohistochemical analysis of TUR-Bt specimens revealed that over 70% of UC cells presented strongly positive results for NACC1. In contrast, normal urothelial cells were weakly positive for NACC1. It was also found that NACC1 expression was lower in invasive UC cells than in non-invasive UC cells. Loss of NACC1 induced vessel invasion in invasive UC tissues. The present results indicate that NACC1 regulated by miR-331-3p contributes to cell proliferation, and is involved in cell migration and invasion. This suggests that NACC1 can serve as a potential target molecule for the prediction and prognosis of UC, and can contribute to effective treatment strategies. MDPI 2018-09-21 /pmc/articles/PMC6210667/ /pubmed/30248959 http://dx.doi.org/10.3390/cancers10100347 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Morita, Kohei
Fujii, Tomomi
Itami, Hiroe
Uchiyama, Tomoko
Nakai, Tokiko
Hatakeyama, Kinta
Sugimoto, Aya
Miyake, Makito
Nakai, Yasushi
Tanaka, Nobumichi
Shimada, Keiji
Yamazaki, Masaharu
Fujimoto, Kiyohide
Ohbayashi, Chiho
NACC1, as a Target of MicroRNA-331-3p, Regulates Cell Proliferation in Urothelial Carcinoma Cells
title NACC1, as a Target of MicroRNA-331-3p, Regulates Cell Proliferation in Urothelial Carcinoma Cells
title_full NACC1, as a Target of MicroRNA-331-3p, Regulates Cell Proliferation in Urothelial Carcinoma Cells
title_fullStr NACC1, as a Target of MicroRNA-331-3p, Regulates Cell Proliferation in Urothelial Carcinoma Cells
title_full_unstemmed NACC1, as a Target of MicroRNA-331-3p, Regulates Cell Proliferation in Urothelial Carcinoma Cells
title_short NACC1, as a Target of MicroRNA-331-3p, Regulates Cell Proliferation in Urothelial Carcinoma Cells
title_sort nacc1, as a target of microrna-331-3p, regulates cell proliferation in urothelial carcinoma cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6210667/
https://www.ncbi.nlm.nih.gov/pubmed/30248959
http://dx.doi.org/10.3390/cancers10100347
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