ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 6 antisense RNA 1 (ST8SIA6-AS1)

ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 6 antisense RNA 1 (ST8SIA6-AS1), also known as APAL or Aurora A/PLK1-associated lncRNA, is a long noncoding RNA transcribed antisense to the ST8SIA6 gene on chromosome 10p12.33. It is overexpressed in various cancers (breast, lung, liver, pancreatic, pituitary adenoma, cholangiocarcinoma, and colorectal) and correlates with poor prognosis. Mechanistically, ST8SIA6-AS1 acts as a molecular scaffold, binding both polo-like kinase 1 (PLK1) and its kinase Aurora A, facilitating Aurora A-mediated phosphorylation of PLK1 and thus promoting cell cycle progression and resistance to apoptosis in cancer cells. Silencing ST8SIA6-AS1 induces mitotic catastrophe and apoptosis in cancer, and locked nucleic acid-based knockdown can inhibit tumor growth in vivo. Additionally, ST8SIA6-AS1 acts as a ceRNA for multiple miRNAs, affecting gene expression networks relevant to tumorigenesis. No currently approved drugs directly target ST8SIA6-AS1, but experimental approaches suggest potential for oligonucleotide therapeutics. Safety concerns include the need for tumor specificity to minimize off-target effects, and uncertainty regarding inhibition effects in normal proliferating tissues. ST8SIA6-AS1’s expression may serve as a biomarker for aggressive cancers and a target for future RNA-based therapies.

Other names

APALAurora A/Polo-like kinase 1-associated lncRNAST8SIA6 antisense RNA 1

Experimental therapies, such as Locked Nucleic Acids (LNAs), aim to knock down ST8SIA6-AS1 expression. This action is designed to inhibit its scaffold function (disrupting PLK1 and Aurora A interaction/phosphorylation) and its ceRNA activity, thereby suppressing cancer cell proliferation and inducing apoptosis.