The potential involvement of the cofactor of BRCA1 in hepatocellular carcinoma pathogenesis

Youssef, Aya; Shawer, Heba; Afify, Alaa M; Amleh, Asma

doi:10.18282/amor.v2.i4.129

Cited by 3 publications

(6 citation statements)

References 37 publications

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“…Furthermore, among four different HCC cell lines ranging in grade and tumorigenicity examined recently by our group, the HepG2 cell line exhibited the highest COBRA1 expression at both the RNA and protein levels. It also demonstrated significantly higher COBRA1 expression relative to the normal hepatocyte cell line, mIHA (31). It was hence used here as our cell model.…”

Section: Silencing Of Cobra1 Does Not Affect the Steady-state Transcrmentioning

confidence: 99%

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

et al. 2017

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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.

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Section: Silencing Of Cobra1 Does Not Affect the Steady-state Transcrmentioning

confidence: 99%

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

et al. 2017

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“…various stages of liver cancer (48). The results have revealed that NELF-B expression is the highest in the early stages, and decreases gradually with the advance in stage of liver cancer, suggesting a possible involvement of NELF-B in the initiation of liver cancer rather than in its progression (48).…”

Section: Discussionmentioning

confidence: 93%

“…The potential role of NELF-B in the pathogenesis of liver cancer has been previously shown (25,48). NELF-B expression has been reported to be upregulated in HCC tissue samples compared with that in paired non-neoplastic tissues (25).…”

Section: Discussionmentioning

confidence: 96%

Role of NELF‑B in supporting epithelial‑mesenchymal transition and cell proliferation during hepatocellular carcinoma progression

et al. 2021

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Negative elongation factor-B (NELF-B), also known as cofactor of BRCA1 (COBRA1), is one of the four subunits of the NELF complex. It interacts with BRCA1, in addition to other transcription complexes in various tissues. The NELF complex represses the transcription of several genes by stalling RNA polymerase II during the early phase of transcription elongation. The role of NELF-B in liver cancer and hepatocellular carcinoma (HCC), the most prevalent type of liver cancer, remains to be elucidated. It has been previously demonstrated that silencing of NELF-B inhibits the proliferation and migration of HepG2 cells. The present study aimed to investigate the consequences of ectopic expression and silencing of NELF-B in liver cancer HepG2 and SNU449 cell lines. Functional assays were performed to examine the effects on gene and protein expression, viability, migration and invasion of cells. Overexpression of NELF-B did not alter the proliferation and migration of HepG2 cells, or the expression of tested genes, indicating that overexpression alone may not be sufficient for altering these features in HepG2 cells. By contrast, knockdown of NELF-B in SNU449 cells resulted in decreased cell proliferation, together with induction of apoptosis and decreased expression levels of Ki-67 and survivin, which are markers of proliferation and inhibition of apoptosis, respectively. Additionally, silencing of NELF-B resulted in a significant decrease in the hallmarks of epithelial-mesenchymal transition (EMT), including cell migration and invasion, and decreased the expression levels of EMT markers, such as N-cadherin, vimentin and β-catenin. Decreased expression levels of forkhead box F2 transcription factor and increased mRNA levels of trefoil factor 1, a putative tumor suppressor, were also detected following the silencing of NELF-B. The current results demonstrated that NELF-B enhanced the manifestation of most hallmarks of cancer, including cell proliferation, migration, invasion and inhibition of apoptosis, indicating its critical role in the progression of HCC.

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“…Despite the advances in clinical classifications of HCC according to patient-related and disease-related criteria (e.g., the Barcelona Clinic liver cancer system) [4] , exploring the biological diversity of HCC have lagged behind. The biological diversity of HCC is expected to come from a diverse set of etiological factors (Hepatitis-B virus, Hepatitis-C virus, non-alcoholic steatohepatitis, and aflatoxin, among other things), all of which are expected to drive the pathogenesis of HCC via various pathways.In the current issue of AMOR, Youssef and co-workers explored the potential involvement of the cofactor of BRCA1 (COBRA1) in HCC pathogenesis [5] . COBRA1 has been incriminated in the pathogenesis of a number of other solid tumors, notably breast cancer.…”

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confidence: 99%

“…In the current issue of AMOR, Youssef and co-workers explored the potential involvement of the cofactor of BRCA1 (COBRA1) in HCC pathogenesis [5] . COBRA1 has been incriminated in the pathogenesis of a number of other solid tumors, notably breast cancer.…”

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confidence: 99%

Dissecting the biological diversity of hepatocellular carcinoma: Opening Pandora's Box

Abdel‐Rahman

2016

Adv Mod Oncol Res

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rimary liver cancer is one of the most commonly occurring malignancies, albeit one with a deadly consequence as it ranks second in males and sixth in females as a cause of cancer-related death [1,2] . In this regard, hepatocellular carcinoma (HCC) constitutes almost 90% of confirmed primary liver cancer cases [3] . Despite the advances in clinical classifications of HCC according to patient-related and disease-related criteria (e.g., the Barcelona Clinic liver cancer system) [4] , exploring the biological diversity of HCC have lagged behind. The biological diversity of HCC is expected to come from a diverse set of etiological factors (Hepatitis-B virus, Hepatitis-C virus, non-alcoholic steatohepatitis, and aflatoxin, among other things), all of which are expected to drive the pathogenesis of HCC via various pathways.In the current issue of AMOR, Youssef and co-workers explored the potential involvement of the cofactor of BRCA1 (COBRA1) in HCC pathogenesis [5] . COBRA1 has been incriminated in the pathogenesis of a number of other solid tumors, notably breast cancer. In the current study, the authors investigated the expression of COBRA1 in several HCC cell lines, ranging from low-to high-grade HCC cell lines. Their results showed that the COBRA1 protein was highly expressed in the low-grade HCC cell line, while significantly down-regulated in high-grade HCC cell lines. This preliminary study indicates that COBRA1 may indeed play a role in HCC pathogenesis and progression, and should be further investigated moving forward. Conflict of interestThe author declares no potential conflict of interest with respect to the research, authorship, and/or publication of this article. References 1.Torre

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The potential involvement of the cofactor of BRCA1 in hepatocellular carcinoma pathogenesis

Cited by 3 publications

References 37 publications

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

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

Role of NELF‑B in supporting epithelial‑mesenchymal transition and cell proliferation during hepatocellular carcinoma progression

Dissecting the biological diversity of hepatocellular carcinoma: Opening Pandora's Box

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