The HEMGN Knockout NCI-H1975 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the NCI-H1975 human lung adenocarcinoma epithelial cell line. This product provides a heterogeneous pool of cells with targeted disruption of HEMGN, enabling loss-of-function studies without clonal selection. The polyclonal format maintains genetic diversity and is suited for functional genomics screening and comparative analyses.
NCI-H1975 is a widely used cell line from a 61-year-old female with non-small cell lung adenocarcinoma, harboring EGFR L858R/T790M and PIK3CA mutations. These oncogenic drivers activate MAPK/ERK and PI3K/AKT pathways, making the cells dependent on EGFR signaling. The line serves as a model for EGFR-mutant lung cancer and TKI resistance studies.
The HEMGN gene encodes a hematopoietic-specific transcription factor predominantly expressed in erythroid and myeloid progenitors, where it plays essential roles in erythropoiesis and myelopoiesis. HEMGN is activated by EPO, GM-CSF, and IL-3 through JAK2-mediated phosphorylation of STAT5, which directly induces HEMGN transcription. Once expressed, HEMGN forms co-regulatory complexes with GATA1, HDAC1, BRG1/SMARCA4, and p300/EP300 to regulate gene expression. Its downstream targets include the oncogenes c-MYC and CCND1 (cyclin D1) and the anti-apoptotic factor BCL2, while it represses the cell cycle inhibitor CDKN1A (p21). Through these mechanisms, HEMGN promotes cell cycle progression and inhibits apoptosis, integrating signals from JAK-STAT, MAPK/ERK, and NF-??B pathways.
Although HEMGN is primarily hematopoietic, its knockout in the NCI-H1975 background permits exploration of non-canonical roles in solid tumors. Given the cell line??s EGFR-driven signaling, HEMGN loss may reveal crosstalk affecting proliferation and survival, potentially implicating targets like c-MYC and BCL2 in lung cancer.
Applicable assays include RNA-seq for transcriptome profiling, RT-qPCR and western blot for target validation, ChIP-seq for genomic localization, and phenotypic assays: proliferation (MTT/BrdU), apoptosis (Annexin V), cell cycle flow cytometry, colony formation, and migration/invasion. These enable gene essentiality studies, drug target validation, and mechanistic investigation in lung adenocarcinoma. For ordering and support, contact Ascent Research.
