Open AccessLnc RNA TPT 1‐ AS 1 promotes tumorigenesis and metastasis in epithelial ovarian cancer by inducing TPT 1 expression
Author(s) -
Wu Weimin,
Gao Hao,
Li Xiaofeng,
Zhu Yong,
Peng Shumin,
Yu Jing,
Zhan Guangxi,
Wang Jiapo,
Liu Na,
Guo Xiaoqing
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.14009
Subject(s) - carcinogenesis , cancer research , metastasis , protein kinase b , downregulation and upregulation , chemistry , cell growth , ovarian cancer , long non coding rna , ectopic expression , cell migration , cell , biology , cell culture , signal transduction , cancer , microbiology and biotechnology , gene , genetics , biochemistry
Increasing numbers of studies have confirmed that long noncoding RNA (lnc RNA ) play a critical role in epithelial ovarian cancer ( EOC ) progression. However, the potential function of the lnc RNA tumor protein translationally controlled 1 ( TPT 1) antisense RNA 1 ( TPT 1‐ AS 1) in EOC is unclear. In this study, we aimed to uncover the biological roles and regulatory mechanisms of TPT 1‐ AS 1 in EOC progression and metastasis. First, TPT 1‐ AS 1 expression was significantly higher in EOC metastatic tissue and cell lines than in their respective control counterparts. In addition, ectopic TPT 1‐ AS 1 expression was strongly associated with unfavorable EOC clinicopathological features, including FIGO stage, tumor size and tumor differentiation. TPT 1‐ AS 1 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 TPT 1‐ AS 1 expression produced the opposite effect in vitro. Mechanistically, TPT 1‐ AS 1 was proven to be primarily distributed in EOC cell nuclei and positively modulated TPT 1 promoter activity and transcription. Moreover, the oncogenic effects of TPT 1‐ AS 1 could be reversed by TPT 1 depletion, and the PI 3K/ AKT signaling pathway downstream of TPT 1 was also altered. These results suggested that TPT 1‐ AS 1 induced EOC tumor growth and metastasis through TPT 1 and downstream PI 3K/ AKT signaling and that TPT 1‐ AS 1 may be a promising therapeutic target for EOC .