Lymphoid enhancer-binding factor 1 antisense RNA 1 (LEF1-AS1)

Lymphoid enhancer-binding factor 1 antisense RNA 1 (LEF1-AS1) is a conserved long non-coding RNA (lncRNA) located at chromosome 4q25, transcribed from the antisense strand of the LEF1 gene locus. It does not encode a protein; instead, it acts as a regulatory molecule influencing gene expression at both transcriptional and post-transcriptional levels. LEF1-AS1 acts as a natural antisense transcript (NAT) that can either promote or suppress tumorigenesis depending on context—though most evidence supports an oncogenic role in various tumors (e.g., glioblastoma, lung, colorectal, and liver cancers). Mechanisms include functioning as a competing endogenous RNA (sponging microRNAs), recruiting epigenetic modifiers (such as PRC2 to the LEF1 promoter, resulting in repressive H3K27me3 marks), and modulating major cancer signaling pathways like PI3K/AKT/mTOR and Wnt/β-catenin. Aberrant expression of LEF1-AS1 correlates with poor prognosis in several cancers, and its inhibition reduces proliferation and invasiveness while promoting apoptosis in cancer cell models, making it a potential diagnostic biomarker and a candidate therapeutic target. No approved drugs target LEF1-AS1 directly, but experimental gene silencing approaches are in preclinical development stages.

Other names

LEF1 antisense RNA 1LEF1NATLEF1 natural antisense transcriptLEF1-AS1 (non-protein coding)

As a therapeutic target, strategies might involve antisense oligonucleotides or RNA interference to knock down LEF1-AS1, thereby inhibiting tumor proliferation, inducing apoptosis, and reducing invasion. LEF1-AS1 modulates target genes and signaling pathways such as PI3K/AKT/mTOR, ERK/MAPK, Wnt/β-catenin, and Hippo pathways, primarily through acting as a ceRNA and via epigenetic mechanisms.