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.
Highlights
The ENCODE project revealed that the majority of the human genome is actively transcribed, but only a small minority of the genome encode proteins [1]
We describe 14 widely reported human solid tumors associated with HOX transcript antisense RNA (HOTAIR) dysregulation, and we briefly review the recent data focusing on breast, lung, liver, gastric, and pancreatic cancer and renal cell carcinoma
HOTAIR is significantly overexpressed in Renal cell carcinoma (RCC) cell lines and clinical tissues compared with normal cell lines and tissues, and HOTAIR has been associated with tumor progression and clinicopathological characteristics of patients [65]
Summary
The ENCODE project revealed that the majority of the human genome is actively transcribed, but only a small minority of the genome encode proteins [1]. Most lncRNAs can regulate gene expression regardless of the subtype of lncRNAs. Accumulating evidence has shown that lncRNAs play a critical role both in physiological processes and in human disease development including cancer. PRC2 is a protein complex, which can mark a gene for transcriptional repression through tri-methylation of histone H3 Lys 27 (H3K27me3) [19, 20]. The LSD1 complex consists of LSD1, CoREST, and REST, and it can lead to repression of gene expression by reducing the tri-methylation of histone H3 Lys 4(H3K4me). HOTAIR provides a molecular scaffold for the assembly of a gene repressor complex consisting of PRC2 and LSD1, thereby silencing its target gene via H3K27 tri-methylation (PRC2 activity) and H3K4 demethylation (LSD1 activity) [17, 29, 31]. HOTAIR acts as a competitive endogenous RNA sponge for a wide variety of miRNAs (Figure 2) and thereby increases the expression of miRNA-targeted genes [34]
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