Non-coding RNA activated by DNA damage (NORAD)

Non-coding RNA activated by DNA damage (NORAD, also known as LINC00657) is a highly conserved and abundantly expressed long non-coding RNA that is rapidly induced by DNA damage[1][3][5]. Its primary function is to preserve genome stability by sequestering PUMILIO RNA binding family proteins and interacting with other factors such as the RNA binding motif protein RBMX[1][5]. Loss of NORAD results in chromosomal instability, aneuploidy, and defects in cell cycle progression[1][3][5]. NORAD plays a pivotal role in numerous cancer types, where it can act as a regulator of cell proliferation, apoptosis, migration, invasion, and chemoresistance, mostly through its activity as a molecular "sponge" for tumor-suppressive microRNAs and its influence on major signaling pathways like TGF-β and PI3K/Akt[1][2][3][6]. NORAD is considered a promising diagnostic, prognostic, and possibly therapeutic target in oncology, but is not a receptor, enzyme, or transporter in the classical sense—rather, it is a regulatory non-protein-coding RNA. No approved drugs directly target NORAD, but its expression modulates cancer cell response to common chemotherapeutic agents such as doxorubicin and cisplatin[1].

Other names

LINC00657Long intergenic non-protein coding RNA 657Long non-coding RNA 657Non-coding RNA activated by DNA damage

Competing endogenous RNA (ceRNA) mechanism: sequestration ("sponging") of tumor suppressor microRNAs (e.g., miR-199a-3p, miR-608, miR-155-5p, miR-590-3p, miR-144-3p, miR-202-5p, miR-190a-3p)[1][2][6]; Indirect modulation of oncogenic signaling pathways: STAT, TGF-β, PI3K/Akt/mTOR[1]; Regulation of genome stability via interaction with PUMILIO proteins and RBMX, affecting mitosis, chromosome segregation, DNA repair[1][3][5]