Original ArticleThe long non-coding RNA 91H increases aggressive phenotype of breast cancer cells and up-regulates H19/IGF2 expression through epigenetic modifications

•91H RNA have an oncogenic role in breast cancer.•91H RNA regulates both H19 and IGF2 expression.•91H RNA prevents epigenetic modifications on maternal allele.•91H RNA allows the maintenance of genomic imprinting.

Numerous genomic imprinting loci are regulated by long non-coding RNA (lncRNA). We have previously identified a new lncRNA at the H19/IGF2 locus transcribed in H19 antisense orientation and named 91H. This RNA is conserved among mammals. In mice, 91H regulates positively IGF2 expression from a novel promoter. However, in human the function of 91H at the H19/IGF2 locus remains largely undeciphered.Here, we observed that 91H, H19 and IGF2 are overexpressed in breast tumors. By using 91H-knockdown breast cancer cells, we demonstrated that 91H exerts oncogenic properties by promoting cell growth, migration and invasion as well as tumor growth in xenografted immunodeficient mouse model. Moreover, 91H-knockdown reduces the expression of H19 and IGF2 in breast cancer cells. By chromatin-immunoprecipitation and methylation studies, we found that 91H expression prevents histone and DNA methylation on the maternal allele at the H19/IGF2 locus. These results indicate that 91H, through epigenetic modifications, is responsible of the maintenance of H19/IGF2 genomic imprinting allowing the allele-specific expression of H19 and IGF2. Taken together, overexpression of 91H in breast cancer and 91H-induced epigenetic modifications on H19/IGF2 locus suggest that 91H may play essential role in breast cancer development. Further studies are needed to investigate their role in terms of diagnosis and therapeutic.