Large intervening non-coding RNA HOTAIR is an indicator of poor prognosis and a therapeutic target in human cancers

Abstract

In the human genome, the fraction of protein-coding genes that are stably transcribed is only up to 2%, with the remaining numerous RNAs having no protein-coding function. These non-coding RNAs (ncRNAs) have received considerable attention in cancer research in recent years. Breakthroughs have been made in understanding microRNAs and small interfering RNAs, but larger RNAs such as long ncRNAs (lncRNAs) remain an enigma. One lncRNA, HOX antisense intergenic RNA (HOTAIR), has been shown to be dysregulated in many types of cancer, including breast cancer, colorectal cancer, and hepatoma. HOTAIR functions as a regulatory molecule in a wide variety of biological processes. However, its mechanism of action has not been clearly elucidated. It is widely believed that HOTAIR mediates chromosomal remodeling and coordinates with polycomb repressive complex 2 (PRC2) to regulate gene expression. Further study of HOTAIR-related pathways and the role of HOTAIR in tumorigenesis and tumor progression may identify new treatment targets. In this review, we will focus on the characteristics of HOTAIR, as well as data pertaining to its mechanism and its association with cancers.

Figure 1

Possible origins of lncRNA. (A) acquire frame disruptions and transform into a functional noncoding RNA; (B) two untranscribed and previously well-separated sequence regions are juxtaposed through chromosome rearrangement; (C) generates either a functional noncoding retrogene or a nonfunctional noncoding retropseudo-gene, resulting from duplication of a noncoding gene by retrotransposition; (D) to occur neighboring repeats; (E) by inserting a transposable element.

Figure 2

Possible mechanisms of lncRNA function. lncRNAs can (1) interfere with downstream gene transcription by inhibiting RNA polymerase II recruitment or (2) promote downstream gene expression by inducing chromatin remodeling and histone modifications; (3) An antisense lncRNA can modulate alternative splicing patterns by hybridizing to the complementary transcript; (4) Hybridization of lncRNA and mRNA allows Dicer to generate endogenous siRNAs; lncRNAs can bind to protein partners to (5) modulate protein activity; (6) serve as structural components; or (7) alter protein localization; (8) lncRNAs can generate small RNA precursors through certain processes.