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

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 pathwa