LncRNA FAM83H-AS1 promotes triple-negative breast cancer progression by regulating the miR-136-5p/metadherin axis.

Abstract

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.

• Authors: Chunyong Han, Yiwei Fu, Ni Zeng, Jian Yin, Qian Li
• Journal: Aging (Aging (Albany NY)) Vol. 12 Issue 4 Pg. 3594-3616 (02 17 2020) ISSN: 1945-4589 [Electronic] United States
• PMID: 32074085 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• FAM83h protein, mouse
• MIRN136 microRNA, human
• MTDH protein, human
• Membrane Proteins
• MicroRNAs
• Proteins
• RNA, Long Noncoding
• RNA-Binding Proteins

Topics

• Animals
• Cell Line, Tumor
• Cell Movement (genetics)
• Cell Proliferation (genetics)
• Databases, Genetic
• Disease Progression
• Female
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Humans
• Membrane Proteins (genetics)
• Mice
• MicroRNAs (genetics)
• Neoplasm Invasiveness (genetics, pathology)
• Proteins (genetics)
• RNA, Long Noncoding (genetics)
• RNA-Binding Proteins (genetics)
• Triple Negative Breast Neoplasms (genetics, pathology)