The IGF2BP3 Knockout NCI-H1703 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population targeting the IGF2BP3 gene in the NCI-H1703 human lung squamous cell carcinoma line. Generated by CRISPR/Cas9-mediated gene disruption, this heterogeneous pool avoids clonal selection artifacts, providing a population-level loss-of-function model for studying IGF2BP3-dependent biology.
NCI-H1703 is a malignant epithelial cell line derived from a patient with lung squamous cell carcinoma, widely used to study squamous lung cancer biology, drug response, and metastasis. The polyclonal knockout preserves the parental line’s intrinsic heterogeneity, offering a physiologically relevant context for functional genomics.
IGF2BP3 (IMP3) is an oncofetal RNA-binding protein that recognizes N6-methyladenosine (m6A) modifications and binds the 3′ UTR of target mRNAs to enhance their stability and translation. It acts downstream of c-MYC and MAPK/ERK signaling, and is negatively regulated by let-7 microRNAs. IGF2BP3 interacts with paralogs IMP1 and IMP2, translation initiation factor eIF4E, and HNRNP family members to form ribonucleoprotein complexes that protect oncogenic transcripts such as CD44, MYC, PROM1, and IGF1R from degradation. This protein also modulates mTORC1 activity and reinforces WNT/??-catenin signaling by stabilizing ??-catenin and promoting LEF1/TCF-dependent transcription. Through these multivalent interactions, IGF2BP3 coordinates growth signals with mRNA metabolism to sustain malignant phenotypes.
In the NCI-H1703 squamous cell carcinoma context, loss of IGF2BP3 destabilizes target mRNAs, decreasing the expression of CD44, MYC, and IGF1R proteins, which are critical for tumor cell proliferation, survival, and motility. Consequently, this polyclonal knockout population displays impaired colony formation, migration, and invasion capabilities. The model faithfully recapitulates post-transcriptional dysregulation observed in lung cancer and serves as a robust platform for mechanistic dissection and therapeutic target assessment.
Applications include RNA immunoprecipitation (RIP) to profile binding partners, RT-qPCR and western blotting to measure target changes, cell-based assays for migration/invasion and colony formation, and RNA stability analyses. The polyclonal format supports high-throughput screens for synthetic lethal interactions or chemosensitizers. For additional details, contact Ascent Research.
