HOTAIR (HOX transcript
antisense RNA) plays a critical role in
chromatin dynamics through the interaction with
histone modifiers resulting in transcriptional gene silencing. The promoter of the HOTAIR gene contains multiple
estrogen response elements (EREs) and is transcriptionally activated by
estradiol in
estrogen receptor-positive
breast cancer cells. HOTAIR competes with BRCA1, a critical
protein in
breast cancer and is a critical regulator of genes involved in epithelial-to-mesenchymal transition. It mediates an oncogenic action of c-Myc, essential for breast
carcinogenesis. The carcinogenic action of HOTAIR was confirmed in
breast cancer stem-like cells, in which it was essential for self-renewal and proliferation. Several
miRNAs regulate the expression of HOTAIR and HOTAIR interacts with many
miRNAs to support
cancer transformation. Many studies point at miR-34a as a major component of HOTAIR-
miRNAs-
cancer cross-talk. The most important role of HOTAIR can be attributed to
cancer progression as its overexpression stimulates invasion and
metastasis. HOTAIR can regulate autophagy, important for
breast cancer cells survival, through the interaction with
miRNAs specific for autophagy genes and directly with these genes. The role of HOTAIR-mediated autophagy in
breast cancer progression can be underlined by its interaction with
matrix metalloproteinases, essential for
cancer invasion, and β-
catenin can be important for this interaction. Therefore, there are several mechanisms of the interplay between HOTAIR and autophagy important for
breast cancer, but further studies are needed to determine more details of this interplay.