Cyclin E1 messenger RNA (CCNE1 mRNA) (CCNE1 mRNA)

Cyclin E1 messenger RNA (CCNE1 mRNA) is the transcript encoding the Cyclin E1 protein, a pivotal regulator of the G1 to S phase transition in the eukaryotic cell cycle (UniProt, 2024). In normal physiology, CCNE1 mRNA levels fluctuate periodically, peaking at the G1/S boundary to activate Cyclin-Dependent Kinase 2 (CDK2), which phosphorylates the retinoblastoma (Rb) protein to initiate DNA synthesis (NIH, 2023). In various malignancies, particularly high-grade serous ovarian cancer (HGSOC) and triple-negative breast cancer (TNBC), CCNE1 is frequently overexpressed or amplified, leading to constitutive CDK2 activation, genomic instability, and resistance to standard-of-care treatments like platinum-based chemotherapy and CDK4/6 inhibitors (PubMed, 2023). While the Cyclin E1 protein itself lacks enzymatic activity and is difficult to target with small molecules, its mRNA represents a direct target for therapeutic intervention via antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) currently in preclinical development (Frontiers in Oncology, 2024). Furthermore, CCNE1 mRNA expression levels serve as a primary predictive biomarker for selecting patients in clinical trials for next-generation selective CDK2 inhibitors (e.g., PF-07104091, BLU-222) and other synthetic lethality-based agents targeting replication stress, such as WEE1 and PKMYT1 inhibitors (ASCO, 2024).

Other names

G1/S-specific cyclin-E1 mRNACCNE mRNACyclin E1 transcriptCCNE1 transcript

CDK2 inhibition, WEE1 inhibition, PKMYT1 inhibition, RNA interference, Antisense-mediated degradation