KDM4A antisense RNA 1 (KDM4A-AS1)

KDM4A antisense RNA 1 (KDM4A-AS1) is a long non-coding RNA transcribed antisense to the KDM4A locus, located near the 3’ UTR of KDM4A. KDM4A-AS1 is aberrantly overexpressed in multiple cancers, including castration-resistant prostate cancer and hepatocellular carcinoma, where it acts as a tumor promoter associated with poor clinical outcomes[2][3]. Mechanistically, KDM4A-AS1 regulates cancer cell proliferation, migration, and invasion, at least in part by stabilizing key oncogenic proteins such as androgen receptor splice variants in prostate cancer, or enhancing KPNA2/AKT signaling in liver cancer. It is hypoxia-inducible and can function as a competing endogenous RNA to sequester specific microRNAs (notably miR-411-5p). Direct targeting of KDM4A-AS1 with antisense oligonucleotides is being investigated as a novel treatment strategy for drug-resistant cancers, restoring sensitivity to therapies such as enzalutamide in prostate cancer models while suppressing tumor growth and metastasis in preclinical hepatocellular carcinoma[2][3][6]. KDM4A-AS1 is considered a molecular biomarker of aggressive, therapy-resistant forms of cancer and represents a promising therapeutic target in oncology.

Other names

KDM4A-AS1KDM4A antisense RNA 1KDM4A-ASLong non-coding RNA KDM4A-AS1

Antisense oligonucleotides downregulate KDM4A-AS1, leading to decreased AR/AR-Vs protein stabilization and increased proteasomal degradation, which restores sensitivity to androgen deprivation therapy in prostate cancer. In HCC, inhibition of KDM4A-AS1 impairs the miR-411-5p/KPNA2/AKT pathway, suppressing proliferation and metastasis.