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Stopping Cancer Cells Before They Start? Inhibitor Of Gene Regulator Discovered

Date:
September 25, 2008
Source:
North Carolina State University
Summary:
A chemist has discovered a molecule that can potentially stop the production of cancer cells at the very beginning of the process by switching off the gene regulators responsible for turning healthy cells into cancer cells. The discovery could lead to the development of drugs that can treat some of the deadliest forms of cancer, including brain cancer.

North Carolina State University chemist has discovered a molecule that can potentially stop the production of cancer cells at the very beginning of the process by switching off the gene regulators responsible for turning healthy cells into cancer cells. The discovery could lead to the development of drugs that can treat some of the deadliest forms of cancer, including brain cancer.

Dr. Alex Deiters, assistant professor of chemistry at NC State, and colleagues at the Wistar Institute of Philadelphia believed that genetic regulators known as microRNAs would be an excellent target for cancer therapies, based on their importance in the process of "programming" a gene, also known as gene regulation.

Thus, miRNAs represent a largely unexplored class of targets for the development of therapeutics and diagnostics, says Huang, an assistant professor in Wistar's Molecular and Cellular Oncogenesis Program.

"This is a totally novel target," he says. "It's very understudied, and still in its infancy, but its potential is tremendous. Because miRNAs have the ability to shut down genes and prevent their expression, they may ultimately provide a target for therapies that are more selective than conventional chemotherapy drugs and have fewer side effects."

MicroRNAs, or miRNAs, are small, single-stranded molecules of about 20 nucleotides – like miniature strands of DNA – that reside in every cell in the human body. These molecules are involved in more than 30 percent of all gene regulatory processes, and direct the translation of genes. When miRNAs are misregulated – either overrepresented or underrepresented – particular genes can be over or under expressed, and cancer can be the result.

The researchers targeted a particular microRNA, called miRNA-21, linked to cancers such as glioblastoma, an aggressive, hard-to-treat form of cancer which is responsible for 52 percent of all brain tumors. MiRNA-21 is responsible for the cancer cells' rapid growth, because it prevents the cancer cells from undergoing apoptosis, or cell death. By stopping the production of miRNA-21, the researchers hoped, they would induce cell death in the glioblastoma cells.

Deiters and colleagues tested more than 1,200 separate compounds before finally coming up with a molecule that decreased miRNA-21 levels by 80 percent. Not only did the compound work to decrease the level of miRNA-21, it presumably worked by inhibiting the transcription of the miRNA itself, without affecting any other miRNAs. While the compound doesn't destroy glioblastoma cells outright, decreasing the level of miRNA-21 removes the cells' anti-apoptotic factor, potentially making them more susceptible to traditional cancer therapy.

"Essentially we have discovered the first small molecule that inhibits miRNA function. Moreover, our inhibitor of miRNA-21 is specific to that particular miRNA and disrupts the transcription of that specific miRNA" Deiters says. "The work represents a real paradigm change in the way we approach cancer drug discovery."


Story Source:

The above story is based on materials provided by North Carolina State University. Note: Materials may be edited for content and length.


Journal Reference:

  1. Dr. Alexander Deiters, Dr. Qihong Huang. Small-Molecule Inhibitors of MicroRNA miR-21 Function. Angewandte Chemie, (in press)

Cite This Page:

North Carolina State University. "Stopping Cancer Cells Before They Start? Inhibitor Of Gene Regulator Discovered." ScienceDaily. ScienceDaily, 25 September 2008. <www.sciencedaily.com/releases/2008/09/080924184657.htm>.
North Carolina State University. (2008, September 25). Stopping Cancer Cells Before They Start? Inhibitor Of Gene Regulator Discovered. ScienceDaily. Retrieved April 24, 2014 from www.sciencedaily.com/releases/2008/09/080924184657.htm
North Carolina State University. "Stopping Cancer Cells Before They Start? Inhibitor Of Gene Regulator Discovered." ScienceDaily. www.sciencedaily.com/releases/2008/09/080924184657.htm (accessed April 24, 2014).

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