Ribonucleoside-diphosphate reductase large subunit (RRM1) mRNA (RRM1 mRNA)

Ribonucleoside-diphosphate reductase large subunit (RRM1) mRNA is the transcript encoding the regulatory and catalytic subunit of the ribonucleotide reductase (RR) enzyme complex. RR is the rate-limiting enzyme responsible for converting ribonucleoside diphosphates into deoxyribonucleoside diphosphates, which are essential precursors for DNA synthesis and repair (UniProt P23921; PubMed: 15150570). High levels of RRM1 mRNA and its corresponding protein are frequently associated with poor prognosis and resistance to nucleoside analog chemotherapies, such as gemcitabine, in various cancers including non-small cell lung cancer and pancreatic cancer (PubMed: 17332331). Consequently, RRM1 mRNA has been identified as a therapeutic target for antisense oligonucleotides like GTI-2040 (LOR-2040), which aim to reduce RRM1 protein levels to inhibit tumor growth and overcome drug resistance (PubMed: 16432181). By depleting the pool of available dNTPs, targeting RRM1 mRNA disrupts the cell cycle and enhances the efficacy of DNA-damaging agents (PubMed: 12124337). This approach provides a method to specifically modulate the expression of a key metabolic enzyme that is otherwise difficult to target with small molecules. Clinical studies have explored the use of RRM1 mRNA-targeting agents in combination with standard chemotherapy to improve patient outcomes in refractory solid tumors. Monitoring RRM1 mRNA levels serves as a potential biomarker for predicting response to gemcitabine-based regimens.

Other names

Ribonucleotide reductase M1 mRNAR1 mRNARRM1 transcriptRibonucleotide reductase catalytic subunit mRNA

Antisense oligonucleotide-mediated mRNA degradation via RNase H activation, resulting in the downregulation of RRM1 protein expression and subsequent inhibition of DNA synthesis and repair (PubMed: 16432181).