Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH PUBLISHING LLC
GLOBETECH PUBLISHING LLC
PZ HTL SA

Growth and Spread of Ovarian Cancer Mediated by a Specific MicroRNA

By BiotechDaily International staff writers
Posted on 22 Jan 2014
Cancer researchers have linked the gene silencing activity of a specific microRNA (miRNA) to TGF-beta (transforming growth factor beta)-mediated molecular pathways that support the growth and spread of ovarian cancer.

MicroRNAs (miRNAs) are a small noncoding family of 19- to 25-nucleotide RNAs that regulate gene expression by targeting mRNAs in a sequence specific manner, inducing translational repression or mRNA degradation, depending on the degree of complementarity between miRNAs and their targets. Many miRNAs are conserved in sequence between distantly related organisms, suggesting that these molecules participate in essential processes. In fact, miRNAs have been shown to be involved in the regulation of gene expression during development, cell proliferation, apoptosis, glucose metabolism, stress resistance, and cancer.

Investigators at Case Western Reserve University (Cleveland, OH, USA) reported in a study published in the January 7, 2014, online edition of the journal Nature Communications that the microRNA miR-181a promoted TGF-beta-mediated epithelial-to-mesenchymal transition (a step critical to cancer spread) via repression of its functional target, the gene SMAD7.

TGF-beta acts as an antiproliferative factor in normal epithelial cells and at early stages of cancer development. When a cell is transformed into a cancer cell, parts of the TGF-beta signaling pathway are mutated, and TGF-beta no longer controls the cell. These cancer cells and surrounding stromal cells begin to proliferate. Both types of cell increase their production of TGF-beta. This TGF-beta acts on the surrounding stromal cells, immune cells, endothelial and smooth muscle cells. It causes immunosuppression and angiogenesis, which makes the cancer more invasive.

The SMAD7 gene product generally shuts down the TGF-beta signaling pathway. However, when miR-181a silences the expression of SMAD7, TGF-beta is not suppressed and metastasis is promoted.

"We found that this (miR-181a) was one of the top expressing microRNAs in tumors from patients who recurred within the first six months after treatment," said senior author Dr. Analisa DiFeo, assistant professor of general medical science-oncology at Case Western Reserve University. "We also found higher levels in recurrent tumors compared to primary tumors in the women we tested. By looking at the expression of this microRNA in tumor samples, we get an idea of which women may respond to standard chemotherapy and which are at a high risk for recurrence. This helps guide treatment decisions and improve survival rates."

"We are now looking for small molecules that can block the interaction between miR-181a and SMAD 7, stop TGF-beta activation and prevent this micro-RNA from spreading and disseminating ovarian cancer," said Dr. DiFeo.

Related Links:

Case Western Reserve University



comments powered by Disqus

Channels

Drug Discovery

view channel
Image: Disruption and removal of malaria parasites by the experimental drug (+)-SJ733 (Photo courtesy of the University of California, San Francisco).

Experimental Antimalaria Drug Induces the Immune System to Destroy Infected Red Blood Cells

An experimental drug for the treatment of malaria was found to induce morphological changes in infected erythrocytes that enabled the immune system to recognize and eliminate them. Investigators at... Read more

Biochemistry

view channel

Blocking Enzyme Switch Turns Off Tumor Growth in T-Cell Acute Lymphoblastic Leukemia

Researchers recently reported that blocking the action of an enzyme “switch” needed to activate tumor growth is emerging as a practical strategy for treating T-cell acute lymphoblastic leukemia. An estimated 25% of the 500 US adolescents and young adults diagnosed yearly with this aggressive disease fail to respond to... Read more

Business

view channel

R&D Partnership Initiated to Reduce Development Time for New Drugs

nanoPET Pharma, GmbH (Berlin, Germany) signed an open-ended framework contract with the international pharmaceutical company Boehringer Ingelheim (Ridgefield, CT, USA). By developing customized contrast agents for research in both basic and preclinical studies, nanoPET Pharma will contribute to the enhancement of Boehringer... Read more
 
Copyright © 2000-2014 Globetech Media. All rights reserved.