Cofactor of BRCA1 as a modulator of hepatocellular carcinoma growth and migration

Cofactor of BRCA1 (COBRA1) is one of the four subunits that make up the Negative Elongation Factor Complex (NELF) which is involved in the stalling of RNA polymerase II early during transcription elongation. As such, COBRA1 is able to regulate a substantial number of genes involved in a number of pathways, including cell cycle control, metabolism, cell proliferation and DNA repair. In the field of cancer, the role of COBRA1 is not yet fully understood. The aim of our study was to investigate the functional role of COBRA1 in the tumorigenesis of hepatocellular carcinoma (HCC). We investigated the gene expression pattern of COBRA1 in HCC tumors using the publicly available Oncomine Cancer Microarray Database. Results from three different microarray datasets reveal the frequent overexpression of COBRA1 in HCC tumors versus their normal counterparts. To elucidate the biological significance for this overexpression in HCC, RNA interference was used to silence the expression of COBRA1 in the well differentiated HCC cell line, HepG2. The silencing efficiency was confirmed by both reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis. Interestingly, knockdown of COBRA1 resulted in a significant decrease in cell proliferation, accompanied by a concomitant decrease in the expression of the proliferation marker, Ki-67. A scratch wound healing assay revealed a significant decrease in the migratory potential of the HepG2 cell line in culture upon COBRA1 knockdown. In addition, silencing of COBRA1 was associated with a significant decrease in the expression of survivin, suggesting that survivin might be one of the mechanisms by which COBRA1 mediates its role in the tumorigenicity of HCC. Collectively, data findings presented here highlight an oncogenic role for COBRA1 in hepatocellular carcinoma. To the best of our knowledge, our study provides evidence for the first time to support a positive role for COBRA1 in the growth and migration of HCC

Knockdown of COBRA1 decreases the proliferation and migration of hepatocellular carcinoma cells

Cofactor of BRCA1 (COBRA1) is one of the four subunits that make up the negative elongation factor (NELF) complex that is involved in the stalling of RNA polymerase II early during transcription elongation. As such, it regulates the expression of a substantial number of genes involved in cell cycle control, cellular metabolism and DNA repair. With no DNA binding domain, its capacity to modulate gene expression occurs via its ability to interact with different transcription factors. In the field of cancer, its role is not yet fully understood. In this study, we demonstrate the frequent overexpression of COBRA1 along with the remaining NELF subunits in hepatocellular carcinoma (HCC) tissues relative to non-cancerous liver tissues. To elucidate its biological significance in HCC, RNA interference was utilized to silence COBRA1 expression in the HCC cell line, HepG2. Interestingly, COBRA1 knockdown resulted in a significant decrease in cell proliferation and migration, accompanied by a concomitant reduction in the expression of the proliferation marker, Ki-67. Survivin, a proto-oncogene that is commonly upregulated in almost all human malignancies including HCC, was also significantly downregulated following COBRA1 silencing. This suggests that it might be one of the mechanisms by which COBRA1 mediates its role in HCC. Taken together, our data findings collectively highlight an important role for COBRA1 in supporting HCC proliferation and migration