RNA-seq analysis of doxycycline-inducible BORIS/CTCFL expression in the metastatic melanoma cell line MM057

Brother of Regulator of Imprinted Sites (BORIS) is a DNA binding protein with high similarity to CCCTC binding factor (CTCF), a multifunctional transcription factor that plays an important role in genome organization. Like CTCF, BORIS plays a role in transcriptional regulation. BORIS becomes aberrantly expressed in melanoma with a higher frequency in metastatic tumors compared to primary tumors, which indicates a role for BORIS in melanoma progression. Currently, little is known about the role of BORIS in melanoma. To gain insight into the functional role of BORIS in melanoma we established doxycycline-inducible BORIS expression in the MM057 melanoma cell line that harbors a proliferation-associated transcriptome. Next, we used RNA-seq to investigate BORIS-mediated transcriptional changes. We show that differentially expressed genes are enriched among invasion-related processes and gene signatures, indicating that BORIS expression contributes to an EMT-like switch from a proliferation to invasion-associated transcriptome. In agreement with these findings, we demonstrate that BORIS overexpression leads to reduced proliferation and increased migration and invasion. Taken together, these data indicate that expression of BORIS promotes a switch from a proliferative to invasive state at both the transcriptional and phenotypic level in melanoma cell lines. Overall design: MM057 cells were stably infected with the lentiviral doxycycline-inducible vector pI20 (empty vector; EV) or with the same vector carrying full length human BORIS (BOR). Cell lines were grown for 5 days either with (EVpos and BORpos) or without (EVneg and BORneg) 50ng/ml doxycycline to induce expression and RNA was extracted for RNA-seq (3 biological replicates).