Cerebellar degeneration-related protein 1 antisense RNA (CDR1-AS) (CDR1-AS)

Cerebellar degeneration-related protein 1 antisense RNA (CDR1-AS), also frequently referred to as CiRS-7, is a highly stable circular RNA molecule predominantly expressed in mammalian brain tissues (Memczak et al., 2013, Nature). Unlike linear RNAs, its circular structure protects it from degradation by exonucleases, allowing it to accumulate and exert potent regulatory effects within the cell. Its primary biological role is functioning as a 'super-sponge' for microRNA-7 (miR-7), a key regulator of various developmental and physiological processes (Hansen et al., 2013, Nature). By sequestering miR-7, CDR1-AS indirectly controls the expression of numerous downstream genes involved in neuronal activity, insulin secretion, and cell proliferation (Piwecka et al., 2017, Science). In clinical contexts, dysregulation of CDR1-AS is strongly linked to disease progression. In oncology, its overexpression is associated with increased tumor growth and metastasis in cancers such as hepatocellular carcinoma and colorectal cancer, where it acts as an oncogene by inhibiting the tumor-suppressive effects of miR-7 (Weng et al., 2017, Journal of Hematology & Oncology). Conversely, reduced levels of CDR1-AS have been observed in the brains of patients with Alzheimer's disease, suggesting a role in neurodegeneration (Lukiw, 2013, Frontiers in Genetics). While there are currently no FDA-approved drugs targeting CDR1-AS, it is a high-priority target for experimental RNA-based therapies, including antisense oligonucleotides (ASOs) and siRNA-mediated knockdown, aimed at restoring normal miR-7 regulatory balance in cancer and neurological disorders (Kristensen et al., 2019, Nature Reviews Genetics).

Other names

CiRS-7CDR1asCircular RNA sponge for miR-7Cerebellar degeneration-related 1 antisense

CDR1-AS acts as a competitive endogenous RNA (ceRNA) or 'sponge' that contains approximately 70 conserved binding sites for miR-7. By sequestering miR-7, it prevents the microRNA from binding to and silencing its target messenger RNAs (mRNAs), thereby upregulating the expression of miR-7-regulated genes (Hansen et al., 2013, Nature; Memczak et al., 2013, Nature).