title: Knockdown of COBRA1 decreases the proliferation and migration of hepatocellular carcinoma cells.
abstract: 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.
authors.affiliation: Biotechnology Department, The American University in Cairo, New Cairo 11835, Egypt.
authors.forename: Eman
authors.initials: E
authors.lastname: El Zeneini
authors.affiliation: Biotechnology Department, The American University in Cairo, New Cairo 11835, Egypt.
authors.forename: Sarah
authors.initials: S
authors.lastname: Kamel
authors.affiliation: HPB and Liver Transplant Surgical Department, Faculty of Medicine, Ain Shams University, Cairo 11341, Egypt.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: El-Meteini
authors.affiliation: Biotechnology Department, The American University in Cairo, New Cairo 11835, Egypt.
authors.forename: Asma
authors.initials: A
authors.lastname: Amleh
mesh_terms: D000368:Aged; D019313:BRCA1 Protein / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D011379:Prognosis; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D014408:Biomarkers, Tumor; C000715470:MAS1 protein, human; C411985:NSMF protein, human; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014157:Transcription Factors; C118437:negative elongation factor