Systematic analyses reveal long non-coding RNA (PTAF)-mediated promotion of EMT and invasion-metastasis in serous ovarian cancer
Authors: Haihai Liang
Rui Yang
Chengyu Wang
Yingzhun Chen
Mengxue Yu
Xiaoguang Zhao
Guoyuan Wang
Lei Fang
Hongli Shan
Yunyan Gu
Jian Sun
Journal: Molecular Cancer (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Epithelial-mesenchymal transition; Invasion; Long non-coding RNA; Metastasis; Serous ovarian cancer.
Affiliations: Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, 150081, China., Department of Systems Biology, College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150001, China., Department of Pathology of The Second Affiliated Hospital, Harbin Medical University, Harbin, 150081, China., Department of Pathology of The First Affiliated Hospital, Harbin Medical University, Harbin, 150081, China., Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, China., Department of Systems Biology, College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150086, China. ., Training Center for Students Innovation and Entrepreneurship Education, Harbin Medical University, Harbin, 150086, China. ., Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, 150081, China. .

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. 

Retracted: No

PubPeer comments:
 Found what appear to be some image duplications in figure 6: ![file] ![file] And I hesitate to post this, but I saw some unusual red dots on the cells in figure 3. I m showing one example of that here. Presumably a result of using some figure processing software, but I do not understand the purpose of it being included in this figure. ![file] ,