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LncRNA TPT1‐AS1 promotes tumorigenesis and metastasis in epithelial ovarian cancer by inducing TPT1 expression

Increasing numbers of studies have confirmed that long noncoding RNA (lncRNA) play a critical role in epithelial ovarian cancer (EOC) progression. However, the potential function of the lncRNA tumor protein translationally controlled 1 (TPT1) antisense RNA 1 (TPT1‐AS1) in EOC is unclear. In this stu...

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Autores principales: Wu, Weimin, Gao, Hao, Li, Xiaofeng, Zhu, Yong, Peng, Shumin, Yu, Jing, Zhan, Guangxi, Wang, Jiapo, Liu, Na, Guo, Xiaoqing
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/PMC6500995/
https://www.ncbi.nlm.nih.gov/pubmed/30941821
http://dx.doi.org/10.1111/cas.14009
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author Wu, Weimin
Gao, Hao
Li, Xiaofeng
Zhu, Yong
Peng, Shumin
Yu, Jing
Zhan, Guangxi
Wang, Jiapo
Liu, Na
Guo, Xiaoqing
author_facet Wu, Weimin
Gao, Hao
Li, Xiaofeng
Zhu, Yong
Peng, Shumin
Yu, Jing
Zhan, Guangxi
Wang, Jiapo
Liu, Na
Guo, Xiaoqing
author_sort Wu, Weimin
collection PubMed
description Increasing numbers of studies have confirmed that long noncoding RNA (lncRNA) play a critical role in epithelial ovarian cancer (EOC) progression. However, the potential function of the lncRNA tumor protein translationally controlled 1 (TPT1) antisense RNA 1 (TPT1‐AS1) in EOC is unclear. In this study, we aimed to uncover the biological roles and regulatory mechanisms of TPT1‐AS1 in EOC progression and metastasis. First, TPT1‐AS1 expression was significantly higher in EOC metastatic tissue and cell lines than in their respective control counterparts. In addition, ectopic TPT1‐AS1 expression was strongly associated with unfavorable EOC clinicopathological features, including FIGO stage, tumor size and tumor differentiation. TPT1‐AS1 overexpression remarkably induced cell proliferation, migration and invasion, and significantly attenuated cell adhesion ability in vitro and facilitated nude mouse subcutaneous xenograft growth and intraperitoneal metastasis in vivo, while the downregulation of TPT1‐AS1 expression produced the opposite effect in vitro. Mechanistically, TPT1‐AS1 was proven to be primarily distributed in EOC cell nuclei and positively modulated TPT1 promoter activity and transcription. Moreover, the oncogenic effects of TPT1‐AS1 could be reversed by TPT1 depletion, and the PI3K/AKT signaling pathway downstream of TPT1 was also altered. These results suggested that TPT1‐AS1 induced EOC tumor growth and metastasis through TPT1 and downstream PI3K/AKT signaling and that TPT1‐AS1 may be a promising therapeutic target for EOC.
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spelling pubmed-65009952019-05-10 LncRNA TPT1‐AS1 promotes tumorigenesis and metastasis in epithelial ovarian cancer by inducing TPT1 expression Wu, Weimin Gao, Hao Li, Xiaofeng Zhu, Yong Peng, Shumin Yu, Jing Zhan, Guangxi Wang, Jiapo Liu, Na Guo, Xiaoqing Cancer Sci Original Articles Increasing numbers of studies have confirmed that long noncoding RNA (lncRNA) play a critical role in epithelial ovarian cancer (EOC) progression. However, the potential function of the lncRNA tumor protein translationally controlled 1 (TPT1) antisense RNA 1 (TPT1‐AS1) in EOC is unclear. In this study, we aimed to uncover the biological roles and regulatory mechanisms of TPT1‐AS1 in EOC progression and metastasis. First, TPT1‐AS1 expression was significantly higher in EOC metastatic tissue and cell lines than in their respective control counterparts. In addition, ectopic TPT1‐AS1 expression was strongly associated with unfavorable EOC clinicopathological features, including FIGO stage, tumor size and tumor differentiation. TPT1‐AS1 overexpression remarkably induced cell proliferation, migration and invasion, and significantly attenuated cell adhesion ability in vitro and facilitated nude mouse subcutaneous xenograft growth and intraperitoneal metastasis in vivo, while the downregulation of TPT1‐AS1 expression produced the opposite effect in vitro. Mechanistically, TPT1‐AS1 was proven to be primarily distributed in EOC cell nuclei and positively modulated TPT1 promoter activity and transcription. Moreover, the oncogenic effects of TPT1‐AS1 could be reversed by TPT1 depletion, and the PI3K/AKT signaling pathway downstream of TPT1 was also altered. These results suggested that TPT1‐AS1 induced EOC tumor growth and metastasis through TPT1 and downstream PI3K/AKT signaling and that TPT1‐AS1 may be a promising therapeutic target for EOC. John Wiley and Sons Inc. 2019-04-29 2019-05 /pmc/articles/PMC6500995/ /pubmed/30941821 http://dx.doi.org/10.1111/cas.14009 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
Wu, Weimin
Gao, Hao
Li, Xiaofeng
Zhu, Yong
Peng, Shumin
Yu, Jing
Zhan, Guangxi
Wang, Jiapo
Liu, Na
Guo, Xiaoqing
LncRNA TPT1‐AS1 promotes tumorigenesis and metastasis in epithelial ovarian cancer by inducing TPT1 expression
title LncRNA TPT1‐AS1 promotes tumorigenesis and metastasis in epithelial ovarian cancer by inducing TPT1 expression
title_full LncRNA TPT1‐AS1 promotes tumorigenesis and metastasis in epithelial ovarian cancer by inducing TPT1 expression
title_fullStr LncRNA TPT1‐AS1 promotes tumorigenesis and metastasis in epithelial ovarian cancer by inducing TPT1 expression
title_full_unstemmed LncRNA TPT1‐AS1 promotes tumorigenesis and metastasis in epithelial ovarian cancer by inducing TPT1 expression
title_short LncRNA TPT1‐AS1 promotes tumorigenesis and metastasis in epithelial ovarian cancer by inducing TPT1 expression
title_sort lncrna tpt1‐as1 promotes tumorigenesis and metastasis in epithelial ovarian cancer by inducing tpt1 expression
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6500995/
https://www.ncbi.nlm.nih.gov/pubmed/30941821
http://dx.doi.org/10.1111/cas.14009
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