RETRACTED: Systematic analyses reveal long non-coding RNA (PTAF)-mediated promotion of EMT and invasion-metastasis in serous ovarian cancer (Retracted article. See vol. 22, 2023)

被引:47
作者
Liang, Haihai [1 ]
Zhao, Xiaoguang [1 ]
Wang, Chengyu [2 ]
Sun, Jian [1 ]
Chen, Yingzhun [3 ]
Wang, Guoyuan [4 ]
Fang, Lei [5 ]
Yang, Rui [1 ]
Yu, Mengxue [1 ]
Gu, Yunyan [6 ,7 ]
Shan, Hongli [1 ]
机构
[1] Harbin Med Univ, State Prov Key Labs Biomed Pharmaceut China, Translat Med Res & Cooperat Ctr Northern China,De, Key Lab Cardiovasc Res,Minist Educ,Coll Pharm,Hei, Harbin 150081, Heilongjiang, Peoples R China
[2] Harbin Med Univ, Dept Syst Biol, Coll Bioinformat Sci & Technol, Harbin 150001, Heilongjiang, Peoples R China
[3] Harbin Med Univ, Dept Pathol, Affiliated Hosp 2, Harbin 150081, Heilongjiang, Peoples R China
[4] Harbin Med Univ, Dept Pathol, Affiliated Hosp 1, Harbin 150081, Heilongjiang, Peoples R China
[5] Harbin Med Univ, Affiliated Hosp 2, Dept Obstet & Gynecol, Harbin 150081, Heilongjiang, Peoples R China
[6] Harbin Med Univ, Dept Syst Biol, Coll Bioinformat Sci & Technol, Harbin 150086, Heilongjiang, Peoples R China
[7] Harbin Med Univ, Training Ctr Students Innovat & Entrepreneurship, Harbin 150086, Heilongjiang, Peoples R China
基金
中国国家自然科学基金;
关键词
Serous ovarian cancer; Epithelial-mesenchymal transition; Long non-coding RNA; Invasion; Metastasis; EPITHELIAL-MESENCHYMAL TRANSITION; FIBROSIS; SUBTYPE; NETWORK; TARGETS; CERNA;
D O I
10.1186/s12943-018-0844-7
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Background: A deeper mechanistic understanding of epithelial-to-mesenchymal transition (EMT) regulation is needed to improve current anti-metastasis strategies in ovarian cancer (OvCa). This study was designed to investigate the role of lncRNAs in EMT regulation during process of invasion-metastasis in serous OvCa to improve current anti-metastasis strategies for OvCa. Methods: We systematically analyzes high-throughput gene expression profiles of both lncRNAs and proteincoding genes in OvCa samples with integrated epithelial (iE) subtype and integrated mesenchymal (iM) subtype labels. Mouse models, cytobiology, molecular biology assays and clinical samples were performed to elucidate the function and underlying mechanisms of lncRNA PTAF-mediated promotion of EMT and invasion-metastasis in serous OvCa. Results: We constructed a lncRNA-mediated competing endogenous RNA (ceRNA) regulatory network that affects the expression of many EMT-related protein-coding genes in mesenchymal OvCa. Using a combination of in vitro and in vivo studies, we provided evidence that the lncRNA PTAF-miR-25-SNAI2 axis controlled EMT in OvCa. Our results revealed that up-regulated PTAF induced elevated SNAI2 expression by competitively binding to miR-25, which in turn promoted OvCa cell EMT and invasion. Moreover, we found that silencing of PTAF inhibited tumor progression and metastasis in an orthotopic mouse model of OvCa. We then observed a significant correlation between PTAF expression and EMT markers in OvCa patients. Conclusions: The lncRNA PTAF, a mediator of TGF-beta signaling, can predispose OvCa patients to metastases and may serve as a potential target for anti-metastatic therapies for mesenchymal OvCa patients.
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页数:15
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