Foxm1b siRNA to Inhibit Tumor Cell Proliferation
Hepatocellular Carcinoma (HCC), also known as primary liver cancer or hepatoma, is a cancer that arises from the liver and accounts for 80% to 90% of all liver cancers. Occurring more often in men than women, HCC is mainly prevalent in people 50 to 60 years of age. Contributing factors to the disease include chronic liver disease, viral hepatitis (especially hepatitis B and C), alcohol consumption, fatty liver disease, hemochromatosis, hepatic carcinogens, and toxins. FoxM1B, also known as Forkhead Box (Fox) M1B, is a member of the family of Fox genes, found in all animals ranging from insects to mammals. FoxM1 transcription factor regulates expression of genes involved in controlling cell division. FoxM1B is required for both DNA replication and mitosis. In previous laboratory experiments, deletion of the FoxM1b gene was shown to prevent development of mouse liver cancer in response to chemical carcinogens. This led the researchers to believe that FoxM1B gene plays a role in promoting the growth of tumors in liver cancer as well as other types of cancer.
Description/Details
UIC researchers have discovered a method that inhibits tumor cell proliferation by FoxM1B siRNA in order to diminish the expression of the FoxM1B transcription factor. Research studies demonstrated that the FoxM1B transcription factor is required for proliferated expansion during tumor progression and constitutes a potential new target for therapy of human HCC tumors. The researchers utilize customized siRNA that targets FoxM1B mRNA for degradation, thereby diminishing its expression and leading to reduced FoxM1B protein levels and function. Transfection of cancer cell lines with FoxM1b siRNA resulted in diminished DNA replication and a complete block in progression into mitosis. The authors found that FoxM1b regulates the transcription of the mitotic regulators survivin, aurora B kinase and polo-like kinase, which are all overexpressed in cancer cells and function to prevent tumor cell apoptosis. Inhibitors of polo-like kinase 1 and aurora B kinase are currently in clinical trials to stimulate apoptosis of cancer cells and FoxM1 regulates transcription of both these mitotic regulators. The invention also relates to developing RNA derivatives to create more stable FoxM1B siRNA for use in vivo.
Applications
·Cancer Therapy ·Cancer prevention ·Drug discovery ·Research: Applicable for pharmaceutical companies or academia interested in RNA interference research
Benefits
·Limits the growth of the liver tumors ·Potentially prevents metastases ·Reduces tumor proliferation ·Diminishes the expression of FoxM1B in tumor cells ·Serves as a potential therapy for hepatitis B and C viral infections of the liver