The Long Noncoding RNA HOTAIR in Breast Cancer: Does Autophagy Play a Role?

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.