Presenting Author

Mudassier Ahmad

Presentation Type

Poster

Discipline Track

Translational Science

Abstract Type

Research/Clinical

Abstract

Pancreatic cancer (PanCa) is the third leading cause of cancer-related deaths in the United States. It shows only a marginal survival benefits of 6 months with the available therapeutics. Thus, to understand the biology of PanCa and discovery of new molecular targets will help in designing the new therapeutic strategies for the management of advanced PanCa. Aberrant ribosome biogenesis is the hallmark of many cancers and has been associated with poor prognosis. Cancer cells show significantly high demand of protein synthesis and to meet this demand modify ribosomal machinery at genetic and epigenetic level. The UBTF (upstream binding transcription factor, RNA polymerase I) gene encodes a member of the HMG-box DNA-binding protein family, which plays a critical role in ribosomal RNA (rRNA) transcription. Recent studies provide strong clues of UBTF involvement in cancer cells survival and chemoresistance. However, no study defines its role in pancreatic cancer. Our results demonstrated that UBTF expression was significantly higher in pancreatic tumors than normal pancreatic tissues as analyzed in tissue microarray. We also observed differential overexpression of total and phospho-UBTF in various human PanCa cells compared to normal pancreatic ductal epithelial cells. Next, we generated UBTF knockdown clones of HPAF-II and MiaPaCa-2 cells and characterized by analyzing UBTF and pre-rRNA expression. We observed 80% inhibition of UBTF and pre-rRNA complex expression which indicates the role of UBTF in functioning of RNA Polymerase I (RNA Pol I). kinase array results showed a significant (P

Academic/Professional Position

Fellow

Mentor/PI Department

Immunology and Microbiology

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Translational impact of UBTF in developing new therapeutic strategy for pancreatic cancer treatment

Pancreatic cancer (PanCa) is the third leading cause of cancer-related deaths in the United States. It shows only a marginal survival benefits of 6 months with the available therapeutics. Thus, to understand the biology of PanCa and discovery of new molecular targets will help in designing the new therapeutic strategies for the management of advanced PanCa. Aberrant ribosome biogenesis is the hallmark of many cancers and has been associated with poor prognosis. Cancer cells show significantly high demand of protein synthesis and to meet this demand modify ribosomal machinery at genetic and epigenetic level. The UBTF (upstream binding transcription factor, RNA polymerase I) gene encodes a member of the HMG-box DNA-binding protein family, which plays a critical role in ribosomal RNA (rRNA) transcription. Recent studies provide strong clues of UBTF involvement in cancer cells survival and chemoresistance. However, no study defines its role in pancreatic cancer. Our results demonstrated that UBTF expression was significantly higher in pancreatic tumors than normal pancreatic tissues as analyzed in tissue microarray. We also observed differential overexpression of total and phospho-UBTF in various human PanCa cells compared to normal pancreatic ductal epithelial cells. Next, we generated UBTF knockdown clones of HPAF-II and MiaPaCa-2 cells and characterized by analyzing UBTF and pre-rRNA expression. We observed 80% inhibition of UBTF and pre-rRNA complex expression which indicates the role of UBTF in functioning of RNA Polymerase I (RNA Pol I). kinase array results showed a significant (P

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