Tumour-regulatory role of long non-coding RNA HOXA-AS3

Abstract

Dysregulation of long non-coding RNA (lncRNA) HOXA-AS3 has been shown to contribute to the development of multiple cancer types. Several studies have presented the tumour-modulatory role or prognostic significance of this lncRNA in various kinds of cancer. Overall, HOXA-AS3 can act as a competing endogenous RNA (ceRNA) that inhibits the activity of seven microRNAs (miRNAs), including miR-29a-3p, miR-29 b-3p, miR-29c, miR-218-5p, miR-455-5p, miR-1286, and miR-4319. This relieves the downstream messenger RNA (mRNA) targets of these miRNAs from miRNA-mediated translational repression, allowing them to exert their effect in regulating cellular activities. Examples of the pathways regulated by lncRNA HOXA-AS3 and its associated downstream targets include the WNT/β-catenin and epithelial-to-mesenchymal transition (EMT) activities. Besides, HOXA-AS3 can interact with other cellular proteins like homeobox HOXA3 and HOXA6, influencing the oncogenic signaling pathways associated with these proteins. Generally, HOXA-AS3 is overexpressed in most of the discussed human cancers, making this lncRNA a potential candidate to diagnose cancer or predict the clinical outcomes of cancer patients. Hence, targeting HOXA-AS3 could be a new therapeutic approach to slowing cancer progression or as a potential biomarker and therapeutic target. A drawback of using lncRNA HOXA-AS3 as a biomarker or therapeutic target is that most of the studies that have reported the tumour-regulatory roles of lncRNA HOXA-AS3 are single observational, in vitro, or in vivo studies. More in-depth mechanistic and large-scale clinical trials must be conducted to confirm the tumour-modulatory roles of lncRNA HOXA-AS3 further. Besides, no lncRNA HOXA-AS3 inhibitor has been tested preclinically and clinically, and designing such an inhibitor is crucial as it may potentially slow cancer progression.

Keywords: Biomarker; HOXA-AS3; Therapeutic target; Tumour; ceRNA; lncRNA.