Systematic analyses reveal long non-coding RNA (PTAF)-mediated promotion of EMT and invasion-metastasis in serous ovarian cancer.

Abstract

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 protein-coding 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-β signaling, can predispose OvCa patients to metastases and may serve as a potential target for anti-metastatic therapies for mesenchymal OvCa patients.

• Authors: Haihai Liang, Xiaoguang Zhao, Chengyu Wang, Jian Sun, Yingzhun Chen, Guoyuan Wang, Lei Fang, Rui Yang, Mengxue Yu, Yunyan Gu, Hongli Shan
• Journal: Molecular cancer (Mol Cancer) Vol. 17 Issue 1 Pg. 96 (06 21 2018) ISSN: 1476-4598 [Electronic] England
• PMID: 29929545 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Retracted Publication)

Chemical References

• MIRN25 microRNA, human
• MicroRNAs
• RNA, Long Noncoding
• SNAI2 protein, human
• Snail Family Transcription Factors

Topics

• Animals
• Cell Line, Tumor
• Cystadenocarcinoma, Serous (genetics, pathology)
• Epithelial-Mesenchymal Transition
• Female
• Gene Expression Profiling (methods)
• Gene Expression Regulation, Neoplastic
• High-Throughput Nucleotide Sequencing (methods)
• Humans
• Mice
• MicroRNAs (genetics)
• Neoplasm Invasiveness
• Neoplasm Metastasis
• Neoplasm Transplantation
• Ovarian Neoplasms (genetics, pathology)
• RNA, Long Noncoding (genetics)
• Snail Family Transcription Factors (genetics)
• Up-Regulation