The BMAL1 Knockout Ca Ski Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population engineered to disrupt the BMAL1 gene in the Ca Ski human cervical carcinoma cell line. This polyclonal knockout model serves as a loss-of-function tool for investigating the circadian transcription factor BMAL1 in an epithelial cancer background.
The parental Ca Ski cell line is an adherent epithelial line derived from a human cervical carcinoma and is stably positive for human papillomavirus type 16 (HPV-16). Ca Ski cells are widely used in cancer research to study HPV-mediated oncogenesis, tumor cell biology, and therapeutic responses.
BMAL1 (also known as ARNTL) is a core component of the circadian clock, functioning as a basic helix-loop-helix PAS transcription factor. It heterodimerizes with CLOCK to bind E-box elements, driving rhythmic expression of clock-controlled genes, including downstream targets such as PER1, PER2, CRY1, CRY2, and the metabolic regulators DBP and REV-ERB??. Transcriptional feedback loops involving PER and CRY proteins repress the BMAL1:CLOCK complex, generating endogenous circadian oscillations. BMAL1 activity is modulated by upstream regulators including ROR??/??, REV-ERB??/??, CK1??/??, SIRT1, and CLOCK, and it interacts with cofactors such as NPAS2 and CBP/p300 to coordinate transcriptional programs.
Disruption of BMAL1 in the Ca Ski cervical carcinoma background provides a physiologically relevant system to explore the intersection between circadian dysregulation and cancer. Aberrant BMAL1 expression has been implicated in tumorigenesis, metabolic syndrome, and sleep disorders. In the context of HPV-positive epithelial cells, BMAL1 knockout may influence pathways associated with proliferation, apoptosis, and viral oncogene expression, offering insights into the role of the circadian clock in HPV-related oncogenesis and potential chronotherapeutic vulnerabilities.
This polyclonal knockout cell population is suitable for a range of experimental applications, including dual-luciferase reporter assays to measure E-box transcriptional activity, RT-qPCR and western blotting for expression analysis of BMAL1 and downstream targets, chromatin immunoprecipitation (ChIP-qPCR) to assess BMAL1 binding to E-box elements, and functional assays such as cell proliferation, apoptosis, and cell cycle profiling by flow cytometry. Researchers can employ these cells to dissect circadian gene regulation, evaluate chronotherapeutic drug responses, and model circadian disruption in cancer. For further details or to discuss custom modifications, please contact Ascent Research.
