| Summary: | Background: PolyADP ribosylation (PARylation) by PARP1 is a significant post-translational modification affecting protein function in various cancers. However, PARP1 mediated cellular processes in the context of breast cancer are not fully understood. Method: To identify potential targets of PARP1, we carried out whole transcriptome sequencing with shRNA mediated PARP1 knockdown in triple-negative breast cancer (TNBC) cell line and inhibited PARP1 with a known PARP1 inhibitor, PJ34. Results: Analysis of the transcriptomics data revealed that PARP1 is involved in regulating multiple chemokines under basal conditions, including the chemokine ligand 2 (<i>CCL2</i>). PARP1 knockdown and PJ34 mediated inhibition showed reduced <i>CCL2</i> transcript levels in breast cancer cells, corroborating the findings from the sequencing data. We further showed that PARP1 interacts with the NFκB P65 subunit to regulate transcription of <i>CCL2</i>. Using chromatin immunoprecipitation, we confirm that both PARP1 and P65 localize to the promoter of <i>CCL2</i>, suggesting direct regulation of <i>CCL2</i> promoter activity. CCL2, in turn, can positively affect the PARP1 pathway, as global PARylation levels increased upon CCL2 treatment. Conclusion: Our results indicate crosstalk between PARP1 and CCL2, which is critical for maintaining CCL2 levels in breast cancer cells and subsequently drives cellular invasiveness.
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