Breast cancer is one of the most common cancers among women. Long non-coding RNAs (lncRNAs) are involved in the initiation and development of breast cancer and lncRNA H19 is a potential oncogenic factor; however, the underlying mechanisms remain unknown. In the present study, the regulatory functions of H19 in breast cancer were investigated. We found that H19 was upregulated in breast cancer tissues and cells and associated with poor prognosis. MiR-138 was downregulated in breast cancer tissues and negatively correlated with the expression of H19 and SOX4. Furthermore, SOX4 was upregulated in breast cancer tissues and positively correlated with H19. Downregulated H19 suppressed the proliferation, invasion and migration of breast cancer cells, but promoted cell cycle arrest and apoptosis. Additionally, miR-138 was identified as a direct target of H19 and SOX4; overexpression of miR-138 inhibited the proliferation, invasion and migration of MDA-MB-231 and MCF-7 cells, but promoted apoptosis, which were abrogated by SOX4 overexpression. Downregulated miR-138 induced cell proliferation, invasion and migration, but inhibited apoptosis of MDA-MB-231 and MCF-7 cells, which were promoted by SOX4 overexpression. In addition, miR-138 overexpression reversed the effects of H19 in breast cancer cells; silencing of H19 inhibited tumor growth and downregulate EMT markers in vivo. In summary, H19 was upregulated in breast cancer and associated with poor prognosis. Silencing of H19 inhibited cell proliferation, invasion and migration, but induced cell cycle arrest and apoptosis by regulating miR-138 and SOX4 in breast cancer.
Keywords: Breast cancer; SOX4; apoptosis; cell cycle; invasion; long non-coding RNA H19; microRNA-181; migration; proliferation.