F-box and WD repeat domain-containing protein 7 mRNA (FBXW7 mRNA)

F-box and WD repeat domain-containing protein 7 (FBXW7) mRNA encodes a critical tumor suppressor that serves as the substrate recognition component of the SCF (Skp1-Cullin-F-box) E3 ubiquitin ligase complex (Source 2, 7). The FBXW7 protein is responsible for the proteasomal degradation of several potent oncoproteins, including c-Myc, Cyclin E, Notch1, MCL-1, and mTOR, thereby maintaining cellular homeostasis by regulating cell cycle progression and apoptosis (Source 4, 17). In many human malignancies, FBXW7 function is lost through genetic mutations or, more frequently, through the downregulation of its mRNA by oncogenic microRNAs such as miR-223, miR-155, and miR-25 (Source 1, 8, 14). This loss leads to the stabilization and accumulation of its oncogenic substrates, driving tumor growth, metastasis, and resistance to various chemotherapeutic and targeted agents (Source 6, 9). Therapeutic strategies currently under investigation focus on restoring FBXW7 mRNA levels using miRNA inhibitors or mRNA replacement technologies, as well as targeting the downstream pathways that become hyperactivated in its absence (Source 6, 13). FBXW7 mRNA expression serves as a significant prognostic biomarker, with low levels often correlating with advanced disease stages and poor patient survival across multiple cancer types (Source 3, 7).

Other names

CDC4FBW7AGOSEL10hCdc4hSel-10F-box and WD-40 domain protein 7

Restoration of FBXW7 mRNA expression or stability to promote the ubiquitin-mediated degradation of oncoproteins (c-Myc, Cyclin E, Notch1, MCL-1) or pharmacological inhibition of the downstream effectors that accumulate upon FBXW7 loss (Source 6, 9, 13).