Scientists Identify Role Of microRNA In Cancer Suppression

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Research suggest the potential for a specific, single microRNA (miR-34a) to be used as a drug candidate in cancer therapy to increase programmed cell-death (apoptosis) in the context of the potent tumor suppressor p53.

p53 has been widely accepted as a powerful tumor inhibitor that can prevent or slow the spread of cancer cells by facilitating apoptosis. In this study, activation of p53 in-vivo in mice as well as in cultured human cells induced the expression of a specific microRNA (miR-34a). Based on the likelihood that miR-34a could itself play a role in cellular apoptosis, researchers introduced miR-34a directly into human cancer cell lines to determine its impact on tumor cell behavior. The results clearly demonstrated that overexpression of miR-34a led to increased cancer cell death as well as promoted other important anti-proliferative activities. The ability of miR-34a to promote apoptosis of cancer cells makes it an attractive candidate tumor suppressor. The data presented in Molecular Cell is also supported by recent studies (Gaur et at., 2007, Welch et al. 2007) showing that miR-34a is under-expressed in central nervous system tumors.

"This is a groundbreaking study shedding light on the critical role microRNAs play in fighting cancer and highlights their potential to act as novel drug targets", noted Dr. Dalia Cohen, Global Head of Research and Development at Rosetta Genomics. "By introducing increased amounts of miR-34a into the cell-lines, Rosetta Genomics researchers and the world class team at Weizmann Institute have been able to show that the overexpression of this specific microRNA is directly linked to tumor suppression. Moreover, the results suggest the potential that a synthetic miR-34a-like agent could be used as a cancer therapy. We strongly believe this research continues to validate the opportunities for microRNA-based therapeutics."

"Demonstrating how p53 utilizes microRNAs to stop the growth of tumor cells through facilitating apoptosis, sheds much light on this critical cancer fighting pathway," said Prof. Moshe Oren of the Weizmann Institute, Principal Investigator of this study. "MicroRNAs have been shown to be involved in the most important cellular processes including apoptosis, and this study helps us better understand their important role in the tumor suppression mechanism."

The p53 protein, also known as tumor protein 53 (TP53), is a transcription factor that functions as a major tumor suppressor in mammals. p53 has been described as "the guardian of the genome" referring to its role in maintaining stability by preventing genome mutation. p53 is activated in response to a variety of stress signals, dictating a variety of biochemical and biological outcomes, ranging from effective repair of minor damage to arresting cell cycle progression and induction of apoptotic cell death. Inactivation of the tumor suppressing function of p53 is one of the most frequent genetic alterations in human cancer, and close to half of all human tumors carry p53 gene mutations within their cells. As a transcription factor, p53 can increase or repress the transcription of many hundreds of protein-encoding genes, and this ability is believed to underlie in great part its tumor suppressor functions.

MicroRNAs are a recently discovered, naturally occurring form of RNAi. These small RNAs act as protein regulators and have the potential to form the basis for a new class of diagnostics and therapeutics. Since many diseases are caused by the abnormal activity of proteins, the ability to selectively regulate protein activity through microRNAs could provide the means to treat a wide range of human diseases. In addition, microRNA expression levels have been shown to be correlated with various disease states and to hold great potential as diagnostics and prognostic markers

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Rosetta Genomics is a leader in the development of microRNA-based diagnostics and therapeutics. Founded in 2000, the company's integrative research platform combining bioinformatics and state-of-the-art laboratory processes has led to the discovery of hundreds of biologically validated novel human microRNAs. Building on its strong IP position and strategic alliances with leading biotechnology companies, Rosetta Genomics is working to develop a full range of diagnostic and therapeutic products based on microRNAs. The company's primary focus is in the development of microRNA-based products to diagnose and treResearch suggest the potential for a specific, single microRNA (miR-34a) to be used as a drug candidate in cancer therapy to increase programmed cell-death (apoptosis) in the context of the potent tumor suppressor p53.

p53 has been widely accepted as a powerful tumor inhibitor that can prevent or slow the spread of cancer cells by facilitating apoptosis. In this study, activation of p53 in-vivo in mice as well as in cultured human cells induced the expression of a specific microRNA (miR-34a). Based on the likelihood that miR-34a could itself play a role in cellular apoptosis, researchers introduced miR-34a directly into human cancer cell lines to determine its impact on tumor cell behavior. The results clearly demonstrated that overexpression of miR-34a led to increased cancer cell death as well as promoted other important anti-proliferative activities. The ability of miR-34a to promote apoptosis of cancer cells makes it an attractive candidate tumor suppressor. The data presented in Molecular Cell is also supported by recent studies (Gaur et at., 2007, Welch et al. 2007) showing that miR-34a is under-expressed in central nervous system tumors.

"This is a groundbreaking study shedding light on the critical role microRNAs play in fighting cancer and highlights their potential to act as novel drug targets", noted Dr. Dalia Cohen, Global Head of Research and Development at Rosetta Genomics. "By introducing increased amounts of miR-34a into the cell-lines, Rosetta Genomics researchers and the world class team at Weizmann Institute have been able to show that the overexpression of this specific microRNA is directly linked to tumor suppression. Moreover, the results suggest the potential that a synthetic miR-34a-like agent could be used as a cancer therapy. We strongly believe this research continues to validate the opportunities for microRNA-based therapeutics."

"Demonstrating how p53 utilizes microRNAs to stop the growth of tumor cells through facilitating apoptosis, sheds much light on this critical cancer fighting pathway," said Prof. Moshe Oren of the Weizmann Institute, Principal Investigator of this study. "MicroRNAs have been shown to be involved in the most important cellular processes including apoptosis, and this study helps us better understand their important role in the tumor suppression mechanism."

The p53 protein, also known as tumor protein 53 (TP53), is a transcription factor that functions as a major tumor suppressor in mammals. p53 has been described as "the guardian of the genome" referring to its role in maintaining stability by preventing genome mutation. p53 is activated in response to a variety of stress signals, dictating a variety of biochemical and biological outcomes, ranging from effective repair of minor damage to arresting cell cycle progression and induction of apoptotic cell death. Inactivation of the tumor suppressing function of p53 is one of the most frequent genetic alterations in human cancer, and close to half of all human tumors carry p53 gene mutations within their cells. As a transcription factor, p53 can increase or repress the transcription of many hundreds of protein-encoding genes, and this ability is believed to underlie in great part its tumor suppressor functions.

MicroRNAs are a recently discovered, naturally occurring form of RNAi. These small RNAs act as protein regulators and have the potential to form the basis for a new class of diagnostics and therapeutics. Since many diseases are caused by the abnormal activity of proteins, the ability to selectively regulate protein activity through microRNAs could provide the means to treat a wide range of human diseases. In addition, microRNA expression levels have been shown to be correlated with various disease states and to hold great potential as diagnostics and prognostic markers

Rosetta Genomics is a leader in the development of microRNA-based diagnostics and therapeutics. Founded in 2000, the company's integrative research platform combining bioinformatics and state-of-the-art laboratory processes has led to the discovery of hundreds of biologically validated novel human microRNAs. Building on its strong IP position and strategic alliances with leading biotechnology companies, Rosetta Genomics is working to develop a full range of diagnostic and therapeutic products based on microRNAs. The company's primary focus is in the development of microRNA-based products to diagnose and treat different forms of cancer and infectious diseases.at different forms of cancer and infectious diseases.

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