Introduction: Recently, the significant regulatory effects of lncRNAs on the oncogenesis and growth of tumor have been demonstrated by an increasing number of research projects. A previous study showed that LL22NC03-N64E9.1  could promote the development of colorectal cancer, especially via enhanced cell proliferation. Similarly, this lncRNA should have comparable functions in breast cancer (BC), which requires in-depth investigation. Therefore, this study was designed to explore the correlation of LL22NC03-N64E9.1  with BC.
Methods: qRT-PCR was used to assess the relative expression of LL22NC03-N64E9.1  in BC tissues. Cell viability examination and colony formation experiments were performed to investigate the role of LL22NC03-N64E9.1  in BC cell’s proliferation. Transwell assays were used to explore the effects of LL22NC03-N64E9.1  on BC cell’s migration. RNA immunoprecipitation, chromosome immunoprecipitation assay and rescue experiments were performed to analyze the association of LL22NC03-N64E9.1  with target proteins and genes in BC cells.
Results: We identified that LL22NC03-N64E9.1  is an oncogene, upregulated in BC, which was verified in a cohort of 48 pairs of BC tissues. Based on the loss-of-function experiments, silencing LL22NC03-N64E9.1  expression significantly inhibited malignancy progression. In terms of the mechanism, LL22NC03-N64E9.1  acted on the enhancer of zeste homolog 2  (EZH2 ) by direct binding, which promoted BC cell growth. Furthermore, in the promoters of KLF2 , the trimethylation of H3K27  could be regulated by LL22NC03-N64E9.1  as the mediator.
Conclusion: Relying on the LL22NC03-N64E9.1 /EZH2 /KLF2  pathway, the lncRNA LL22NC03-N64E9.1  was significantly associated with BC development and could, therefore, be a potential therapeutic target to block BC growth.
Keywords: breast cancer, lncRNA, LL22NC03-N64E9.1 , H3K27me3 , KLF2