Cofactor of BRCA1 promotes epithelial-mesenchymal transition and cell proliferation in intermediate stage hepatocellular carcinoma cell line

Hepatocellular carcinoma ranks as one of the most lethal types of cancer worldwide and in Egypt. Being complex and heterogenous clinically and molecularly, HCC has a very poor prognosis, and it lacks adequate diagnostic and prognostic molecular markers. Cofactor of BRCA1 (COBRA1); also known as NELF-B, is one of the NELF complex components that stalls RNA polymerase II during transcription elongation and regulates several processes in the cell. Previous studies have shown the upregulation of COBRA1 in Hepatocellular carcinoma (HCC) compared to healthy liver tissue. It was also shown to support cell proliferation and migration in early stages of HCC. In our study, we investigated the role of COBRA1 in the epithelial-mesenchymal transition (EMT)- a critical process in cancer metastasis, and progression of HCC. Functional analysis was done by silencing the expression of COBRA1 in an intermediate stage HCC cell line SNU449, followed by examining the effect of the knockdown on some cancer hallmarks. COBRA1 knockdown cells showed decreased cell proliferation, induction of apoptosis, accompanied by a downregulation of Ki67, Survivin that mark for proliferation and anti-apoptosis respectively. Moreover, COBRA1 Knockdown cells showed a decrease in cell migration and invasion, accompanied by decreased expression of TWIST1- one of the key transcription factors that mediate EMT. Our results demonstrated that COBRA1 supports cell proliferation, migration and invasion, and inhibits apoptosis, which implicates it has a critical role in the progression of HCC