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MNX1-AS1 is a functional oncogene that induces EMT and activates the AKT/mTOR pathway and MNX1 in breast cancer

Authors Cheng Y, Pan Y, Pan Y, Wang O

Received 18 September 2018

Accepted for publication 16 December 2018

Published 17 January 2019 Volume 2019:11 Pages 803—812

DOI https://doi.org/10.2147/CMAR.S188007

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Cristina Weinberg

Peer reviewer comments 2

Editor who approved publication: Professor Nakshatri


Yue Cheng,1 Yiqi Pan,2 Yiyuan Pan,3 Ouchen Wang1

1Department of Thyroid and Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China; 2Wenzhou Medical University, Wenzhou, China; 3Department of Thyroid and Breast Surgery, Wenzhou People’s Hospital, Wenzhou, China

Purpose: lncRNAs have recently been identified as key regulators of basic biological processes as well as the pathogenesis of various diseases. Previous studies have shown that lncRNA MNX1-AS1 promotes cell migration and invasion in ovarian cancer; however, its role in regulating breast cancer-associated biological processes remains unclear.
Materials and methods: We obtained paired specimens of breast cancer tissues and adjacent normal tissues by modified radical mastectomy from 36 patients, in addition to four breast cancer cell lines (MDA-MB-231, MDA-MB-468, BT-549 and MCF-7). RNA was isolated from these tissues and cell lines and subsequently subjected to quantitative real-time polymerase chain reaction. This was followed by bisulfite deep sequencing. The cells were also transfected with siRNA against MNX1-AS1. The cells were then subject to cell proliferation, Transwell migration and invasion assays. Finally, Western blotting analysis was conducted to determine expression levels of MNX1, 5-cadherin, Snail and Slug.
Results: Our results show that MNX1-AS1 expression was significantly higher in breast cancer tissues than adjacent normal tissues. Moreover, knockdown/overexpression of MNX1-AS1 inhibits/promotes proliferation, migration and invasion of breast cancer cells. MNX1-AS1 and its natural sense transcript MNX1 are expressed synergistically in breast tumor tissues. Our results suggest that MNX1-AS1 is a functional oncogene that induces epithelial–mesenchymal transition, in addition to activating AKT/mTOR pathway and its natural sense transcript MNX1 in breast cancer cells.
Conclusion: Our data indicate that MNX1-AS1 can serve as a novel therapeutic target in breast cancer.

Keywords: MNX1-AS1, breast cancer, oncogene, MNX1, EMT, AKT/mTOR signaling pathway



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