BackgroundBreast cancer is one of the most common cancers worldwide. Long non-coding RNAs and microRNAs act as important regulators in human cancers. This study aims to explore the molecular mechanism among H19, miR-491-5p and zinc finger 703 (ZNF703) in breast cancer.Materials and MethodsQuantitative real-time polymerase chain reaction (qRT-PCR) was conducted to detect the expression of H19, miR-491-5p and ZNF703. Cell Counting Kit 8 (CCK-8) assay was performed to evaluate cell proliferation. Cell apoptosis was assessed by flow cytometry assay. The number of migrated and invaded cells was counted by transwell assay. Dual luciferase reporter assay was carried out to test luciferase activity. Protein level of ZNF703 was measured by Western blot assay.ResultsH19 was highly expressed in breast tissues and cells. H19 knockdown inhibited proliferation, induced apoptosis and blocked migration and invasion. Moreover, H19 bound to miR-491-5p and negatively regulated miR-491-5p expression. MiR-491-5p inhibition abrogated the activities of proliferation, apoptosis, migration and invasion affected by H19 knockdown. Furthermore, miR-491-5p directly targeted ZNF703 and inversely modulated ZNF703 expression. ZNF703 up-regulation rescued the effects of miR-491-5p overexpression on proliferation, apoptosis, migration and invasion. In addition, H19 knockdown reduced ZNF703 expression by targeting miR-491-5p/ZNF703 axis.ConclusionH19 promoted proliferation, migration and invasion and retarded apoptosis of breast cancer cells via sponging miR-491-5p to down-regulate ZNF703 expression.