Abstract
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.
Highlights
The complexity of an eukaryotic organism, which can be measured by the number of different cell types, cannot be directly correlated with the structure of its genome [1,2]
The level of Homeobox Transcript Antisense RNA (HOTAIR) expression was not associated with clinical characteristics of breast cancer in a multivariate analysis, but an association between enhanced HOTAIR expression and lower disease relapse and mortality was found in a univariate analysis. These results suggest that HOTAIR may not be an independent breast cancer marker and requires further research
HOTAIR plays an important role in epigenetic regulation of gene expression through the modification of chromatin structure leading to gene silencing
Summary
The complexity of an eukaryotic organism, which can be measured by the number of different cell types, cannot be directly correlated with the structure of its genome [1,2]. HOTAIRchienmteicraalctmwoditihficLatSioDn1s (olyf shinisetosnpeectaifiilsc dleeamd ettohyclharsoem1aAtin), acohmipstleoxninegdeamndetshilyenlacsineg, wohf icthheis a part of largertrapnrsocrteipitniocnoomf tparlgeext gaennde(sd).emethylases H3 histone at lysine 4 (H3K4demet) These chemical modifications of histone tails lead to chromatin complexing and silencing of the transcription of target gene(s). HOTAIR was suppressed by a direct cleavage by Argonaute 2, RISC (RNA interference silencing complex) catalytic component 2 (AGO2), in the presence of miR-141 [53] This effect is important for the role of HOTAIR in cancer transformation, as miR-141 in contrast to HOTAIR, is considered as a tumor suppressor, so its interaction with HOTAIR can significantly influence the process of malignant transformation, including breast carcinogenesis [54,55,56,57,58,59,60,61,62,63]. HOTAIR was reported to overexpress in glioma cells, and its knockdown resulted in miR-326-mediated suppression of oncogenic effects [66]
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