LncRNA HOTAIR: A Potential Prognostic Factor and Therapeutic Target in Human Cancers

Abstract

Long non-coding RNAs (lncRNAs) are emerging as crucial regulators of gene expression and physiological processes. LncRNAs are a class of ncRNAs of 200 nucleotides in length. HOX transcript antisense RNA (HOTAIR), a trans-acting lncRNA with regulatory function on transcription, can repress gene expression by recruiting chromatin modifiers. HOTAIR is an oncogenic lncRNA, and numerous studies have determined that HOTAIR is highly upregulated in a wide variety of human cancers. In this review, we briefly summarize the impact of lncRNA HOTAIR expression and functions on different human solid tumors, and emphasize the potential of HOTAIR on tumor prognosis and therapy. Here, we review the recent studies that highlight the prognostic potential of HOTAIR in drug resistance and survival, and the progress of therapies developed to target HOTAIR to date. Furthermore, targeting HOTAIR results in the suppression of HOTAIR expression or function. Thus, HOTAIR knockdown exhibits great therapeutic potential in various cancers, indicating that targeting lncRNA HOTAIR may serve as a promising strategy for cancer therapy. We also propose that preclinical studies involving HOTAIR are required to provide a better understanding of the exact molecular mechanisms underlying the dysregulation of its expression and function in different human cancers and to explore effective methods of targeting HOTAIR and engineering efficient and targeted drug delivery methods in vivo.

Keywords: HOTAIR; cancer; drug resistance; knockdown; potential; prognosis; survival; therapy.

Figure 1

Schematic location of lncRNA HOTAIR. The HOTAIR gene is located in the center of the HOXC gene cluster on chromosome 12, specifically between HOXC11 and HOXC12, on the antisense strand. It consists of six exons, and exon 6 contains two domains.

Figure 2

Functions and molecular mechanisms of HOTAIR. The interactions between HOTAIR and its several important partners are summarized. (1) The 5′-end of HOTAIR binds to the PRC2 complex. The 3′-end of HOTAIR binds to the LSD1 complex. H3K27 tri-methylation and H3K4me3 demethylation result from PRC2 complex and LSD1 complex activity, respectively, and cause gene silencing. (2) HOTAIR interacts with E3 ubiquitin ligases, Dzip3 and Mex3b, and facilitates the ubiquitination of Ataxin-1 and Snurportin-1, thereby contributing to their degradation. (3) HOTAIR interacts with miRNAs as a competitive endogenous RNA to promote the expression of miRNA-targeted genes.

Figure 3

The expression of HOTAIR in human cancers. Shown are examples of the organ-specific expression of HOTAIR. The up red arrow indicates an increase in expression.