The IGF2BP3 Knockout HAP1 Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout cell population generated from the human chronic myeloid leukemia-derived near-haploid HAP1 cell line. This product disrupts the gene encoding insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), an oncofetal RNA-binding protein that post-transcriptionally regulates a network of cancer-associated transcripts. The polyclonal format provides a heterogeneous loss-of-function pool, enabling robust population-level phenotypic and molecular analyses without isolating individual clones. This model is designed for researchers studying post-transcriptional gene regulation, mRNA stability, and oncogenic signaling pathways in a hematologic malignancy context.
The HAP1 host cell line is a KBM-7 derivative originating from a patient with chronic myeloid leukemia, characterized by a near-haploid karyotype that simplifies genetic manipulation and interpretation of knockout phenotypes. Its hematopoietic cancer origin makes it particularly relevant for investigating leukemic cell biology, yet the cell line has been widely adopted as a versatile platform for functional genomics across diverse cancer types. The loss of IGF2BP3 in this genetic background offers a physiologically relevant system to study how RNA-binding protein-dependent control of gene expression contributes to malignant transformation and tumor maintenance.
IGF2BP3 functions by binding to the 3?? untranslated regions of target mRNAs such as MYC, CD44, and IGF2, stabilizing these transcripts and enhancing their translation through interactions with eIF4E and ribosomal subunits. Its activity is modulated by upstream signals: WNT3A and ??-catenin promote its transcription via TCF4, while STAT3, NOTCH1, and HIF1?? also contribute to its regulation. IGF2BP3 in turn promotes expression of MYC, CD44, MMP9, and BCL2, integrating mitogenic, anti-apoptotic, and migratory programs. Additionally, IGF2BP3 interacts with RNA-binding proteins like ELAVL1 and HNRNPA2B1, influencing mRNA fate. Consequently, IGF2BP3 acts as a hub in Wnt/??-catenin, PI3K/AKT/mTOR, and MYC transcriptional networks, coupling extracellular signals to post-transcriptional oncogene control.
Ablation of IGF2BP3 in HAP1 cells eliminates stabilization and enhanced translation of its mRNA targets, creating a clean loss-of-function system to study RNA-dependent cancer mechanisms. The near-haploid nature simplifies genetic analysis because a single CRISPR-induced mutation suffices for functional knockout, reducing redundancy and clarifying genotype-phenotype links. This model enables precise dissection of how IGF2BP3 loss alters the transcriptome and proteome without the complexity of aneuploidy or multiple alleles. It is particularly suited for hematopoietic malignancy research and broader RNA-binding protein biology in human cancer.
Researchers can employ this knockout model in diverse applications: RNA immunoprecipitation (RIP) to validate direct mRNA targets, actinomycin D chase to measure mRNA stability, and RNA sequencing to assess transcriptome-wide changes. Functional assays include proliferation (MTT/XTT), Boyden chamber migration/invasion, colony formation, and flow cytometry for cell cycle and apoptosis (Annexin V). These tools facilitate studies on drug resistance, metastatic mechanisms, and RNA-binding protein-driven oncogenic signaling. For further information or to request a quote, contact Ascent Research.
