Functions of lncRNA HOTAIR in lung cancer

Abstract

Long non-coding RNAs (lncRNAs) govern fundamental biochemical and cellular processes. lncRNA HOX transcript antisense RNA (HOTAIR) represses gene expression through recruitment of chromatin modifiers. The expression of HOTAIR is elevated in lung cancer and correlates with metastasis and poor prognosis. Moreover, HOTAIR promotes proliferation, survival, invasion, metastasis, and drug resistance in lung cancer cells. Here we review the molecular mechanisms underlying HOTAIR-mediated aggressive phenotypes of lung cancer. We also discuss HOTAIR's potential in diagnosis and treatment of lung cancer, as well as the challenges of exploiting HOTAIR for intervention of lung cancer.

Figure 1

Isoforms of human HOTAIR transcripts. The USCS Genome Browser track of the human HOTAIR gene is used to illustrate isoforms of the human HOTAIR transcript [47]. The principal transcript RefSeq NR_003716 and two multi-exon HOTAIR variants in the GENCODE catalogue that lack the PRC2-interacting domain and the LSD1-interacting domain are marked by red open rectangles. See text for details.

Figure 2

Molecular mechanisms of the tumor-promoting actions of HOTAIR. The interactions between HOTAIR and its partners are summarized. The length of each exon and positions of the interacting region for each partner are proportional to their length and positions in the principal transcript RefSeq NR_003716 of the human HOTAIR gene. The introns are not drawn proportionally to their length. A green arrow indicates positive regulation of the processes or substrates targeted by the arrow. A red arrow indicates negative regulation of the targeted processes or substrates by the arrow. A red bi-directional arrow is used to illustrate the reciprocal negative regulation between HOTAIR and miR-130a. HOTAIR’s interaction with E3 ubiquitin ligase Mex3b and its substrate Snurportin-1 is not included in the figure because the interaction is mediated through the region that overlaps with the Dzip3-Ataxin-1 interacting domain in HOTAIR. See text for details. PRC2: Polycomb Repressive Complex 2; EZH2: enhancer of zeste homolog 2; HuR: Human antigen R; LSD1: Lysine-Specific Demethylase 1.