The JUN Knockout 786-O Polyclonal Cells constitute a CRISPR/Cas9-edited polyclonal knockout population designed to ablate JUN gene function in the human 786-O renal cell adenocarcinoma line. This heterogeneous pool of gene-disrupted cells provides a loss-of-function model that bypasses clonal selection, enabling robust analysis of JUN-dependent biology with population-level diversity. The product is formatted as a pool of edited cells, suitable for researchers seeking to study JUN contributions in a genomically varied context.
The 786-O cell line is a classic model of clear cell renal cell carcinoma (ccRCC), harboring a mutant VHL tumor suppressor gene that drives constitutive HIF stabilization and oncogenic programs. With adherent epithelial morphology, 786-O cells are used to investigate ccRCC tumor biology, VHL-dependent signaling, and therapeutic responses, offering a relevant background for JUN knockout studies.
JUN encodes c-Jun, a core AP-1 transcription factor subunit that heterodimerizes with c-Fos (FOS), FOSL1, FOSL2, or ATF proteins. Upstream kinases JNK1/2 (MAPK8/9) and ERK1/2 (MAPK3/1) phosphorylate c-Jun upon stimulation by TNF-alpha, IL-1, or growth factors, leading to regulation of downstream targets including CCND1, TP53, BCL2, MMP1, MMP9, VEGFA, and FOS. c-Jun also interacts with CBP/p300 and integrates signaling from MKK4/MAP2K4 and MKK7/MAP2K7, cross-talking with Wnt, TGF-beta, and PI3K-AKT pathways to control proliferation, apoptosis, and stress responses.
In VHL-mutant 786-O cells, JUN disruption impairs AP-1 transcriptional activity, potentially uncoupling MAPK-driven oncogenic signals from HIF-mediated pathways. This knockout model allows dissection of c-Jun-specific contributions to ccRCC phenotypes such as proliferation, survival, and invasion, without confounding from VHL loss. It provides a platform to study how stress-responsive kinases converge on AP-1 to modulate renal cancer progression.
Researchers can apply these polyclonal cells in Western blot, RT-qPCR, and luciferase reporter assays to validate JUN loss and AP-1 activity. Functional assays including proliferation, apoptosis, migration, invasion, and colony formation, along with RNA-seq and ChIP-seq, enable comprehensive analysis of JUN-dependent transcriptomic and cistromic changes. This model facilitates drug target validation, resistance mechanism studies, and stress pathway investigation in renal carcinoma. For additional information, contact Ascent Research.
