The HOTTIP (HOXA transcript at the distal tip) lncRNA: Review of oncogenic roles in human.

HOXA transcript at the distal tip (HOTTIP) is a 3764 nucleotide long non-coding RNA (lncRNA) encoded from a genomic region in the 5' tip of the HOXA locus. This lncRNA has a role in transmission of signals from higher order chromosomal configuration into chromatin codes. HOTTIP directly binds with the WDR5 protein and recruits the WDR5/MLL complexes across the HOXA locus which leads to H3K4 methylation and activation of the transcription of HOXA genes. This lncRNA has a prominent role in the pathogenesis of almost all kinds of cancers. Apart from a single study in glioma cells, all in vitro studies have emphasized on oncogenic roles of HOTTIP in different malignancies. In vivo studies also showed the effect of HOTTIP silencing in reduction of tumorigenicity in all cancer types except from glioma. Results of clinical studies mostly demonstrated up-regulation of this lncRNA in cancer samples compared with non-malignant tissues of the same origin and correlation between its expression levels and patients' outcome. Taken together, HOTTIP is regarded as an oncogenic lncRNA in almost all kinds of cancers and a putative biomarker and therapeutic target in human malignancies.