A PTAL-miR-101-FN1 Axis Promotes EMT and Invasion-Metastasis in Serous Ovarian Cancer

Haihai Liang; Mengxue Yu; Rui Yang; Lu Zhang; Lijia Zhang; Di Zhu; Hongwei Luo; Yaozhen Hong; Tong Yu; Jian Sun; Hongli Shan; Yunyan Gu

doi:10.1016/j.omto.2019.12.002

A PTAL-miR-101-FN1 Axis Promotes EMT and Invasion-Metastasis in Serous Ovarian Cancer

Mol Ther Oncolytics. 2019 Dec 11:16:53-62. doi: 10.1016/j.omto.2019.12.002. eCollection 2020 Mar 27.

Authors

Haihai Liang^{1

2}, Mengxue Yu¹, Rui Yang¹, Lu Zhang^{1

2}, Lijia Zhang¹, Di Zhu¹, Hongwei Luo¹, Yaozhen Hong¹, Tong Yu^{1

2}, Jian Sun^{1

2}, Hongli Shan^{1

2}, Yunyan Gu³

Affiliations

¹ 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, Harbin, Heilongjiang 150081, P.R. China.
² Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.
³ Department of Systems Biology, College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.

Abstract

Long non-coding RNAs (lncRNAs) play vital roles in the metastasis and invasion of cancer cells. Systematic analysis of ovarian cancer (OvCa) expression profiles suggests that deregulation of lncRNA AC004988.1, designated promoting transition-associated lncRNA (PTAL), is involved in OvCa progression. However, the underlying mechanism of PTAL in OvCa remains unknown. In this study, we showed that PTAL was significantly upregulated in mesenchymal subtype samples compared with epithelial subtype samples from TCGA serous OvCa datasets. PTAL expression was positively correlated with the expression of fibronectin1 (FN1), whereas PTAL and FN1 were negatively correlated with miR-101 expression in the mesenchymal OvCa samples. In addition, knockdown of PTAL inhibited cell migration and invasion and blunted the progression of metastasis in vitro. Meanwhile, knockdown of PTAL increased the expression of miR-101 and subsequently inhibited the expression of FN1. Importantly, PTAL positively regulated the expression of FN1 through sponging of miR-101 and promoted OvCa cell metastasis by regulating epithelial-mesenchymal transition. Overall, our study demonstrates the role of PTAL as a miRNA sponge in OvCa and suggests that PTAL may be a potential target for preventing OvCa metastasis.

Keywords: FN1; epithelial-mesenchymal transition; lncRNA PTAL; miR-101; ovarian cancer.