Research Paper Volume 12, Issue 4 pp 3594—3616
LncRNA FAM83H-AS1 promotes triple-negative breast cancer progression by regulating the miR-136-5p/metadherin axis
- 1 Department of Breast Reconstruction, The Sino-Russian Joint Research Center for Oncoplastic Breast Surgery, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Treatment of Tianjin, Tianjin Clinical Research Center for Cancer, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin 300060, China
- 2 Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Treatment of Tianjin, Tianjin Clinical Research Center for Cancer, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin 300060, China
- 3 Department of Cell Biology, Basic Medical College, Tianjin Medical University, Tianjin 300070, China
- 4 Department of Respiratory, Tianjin Fifth Central Hospital, Tianjin 300457, China
received: December 6, 2019 ; accepted: January 27, 2020 ; published: February 17, 2020 ;https://doi.org/10.18632/aging.102832
How to Cite
Copyright © 2020 Han et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
In this study, we evaluated the function and regulation of the long non-coding RNA (lncRNA) FAM83H-AS1 in triple-negative breast cancer (TNBC). Our data show that the FAM83H-AS1 levels are increased in human TNBC cells and tissues. Proliferation, migration, and invasion of TNBC cells are decreased by FAM83H-AS1 suppression, but increased by FAM83H-AS1 overexpression. Bioinformatics analysis revealed that miR-136-5p is a potential target of FAM83H-AS1. MiR-136-5p expression is decreased in TNBC tissues, and its overexpression suppresses TNBC cell proliferation, migration, and invasion. MiR-136-5p suppression reverses the FAM83H-AS1 silencing-mediated inhibition of TNBC cell proliferation, migration, and invasion, suggesting that FAM83H-AS1 exerts its oncogenic effect by inhibiting miR-136-5p. Our data identify metadherin (MTDH) as the target gene of miR-136-5p, and demonstrate that the MTDH expression is increased in human TNBC tissues, which induces proliferation, migration, and invasion of TNBC cells. Importantly, our in vivo data show that FAM83H-AS1 also promotes tumor growth in TNBC mouse xenografts. Together, our results demonstrate that FAM83H-AS1 functions as an oncogenic lncRNA that regulates miR-136-5p and MTDH expression during TNBC progression, and suggest that targeting the FAM83H-AS1/miR-136-5p/MTDH axis may serve as a novel therapeutic target in TNBC.
TNBC: triple-negative breast cancer; lncRNAs: long noncoding RNAs; miR: microRNA; FAM83H-AS1: FAM83H antisense RNA 1; MTDH: Metadherin; qRT-PCR: quantitative real-time PCR; Wt: wild-type; Mut: mutant binding sites; CCK8: Cell Counting Kit-8; GEPIA2: Gene Expression Profiling Interactive Analysis 2; siRNA: small interfering RNA.