A molecule with potential to fight the Ovary cancer and block the tumor cell metastasis process has been described by researchers from Brazil and the United States in the journal Cancer Research.
Known as miR-450a, the small RNA molecule is often poorly expressed in tumors.
However, in vitro and mouse tests have shown that when overexpressed, it can have positive effects on treating the disease by silencing the expression of genes involved in cell migration and tumor energy metabolism.
The study was conducted at the Cell Therapy Center (CTC), a Fapesp-funded Research, Innovation and Dissemination Center at the University of São Paulo (USP) in Ribeirão Preto.
It was collaborated by Markus Hafner, professor at the National Institute of Health (NIH) Laboratory of Muscle Stem Cells and Gene Regulation.
“It's a promising molecule. We can develop, in the future, using nanotechnology, therapeutic strategies against ovarian cancer, ”said Wilson Araújo da Silva Junior, CTC researcher and study coordinator.
Because it is initially asymptomatic, ovarian cancer tends to be detected at an advanced stage. Currently, the main weapon in treatment is surgery.
“MiR-450a, whether or not associated with chemotherapy, may contribute as neoadjuvant therapy (preoperative treatment), increasing preoperative response rates. In more advanced cases, the risk of disease progression or death may be reduced, with side effects possibly less than those of chemotherapy. Another interesting point of the molecule is the ability to block the metastasis process, ”said Silva Junior.
So-called microRNAs, such as miR450a, are small RNA molecules that do not encode protein but perform regulatory function in the genome and, as a result, in various intracellular processes.
The strategy of action of these molecules is to bind to messenger RNA expressed by a gene, preventing their translation into protein.
In vitro and in vivo tests performed at the Cell Therapy Center, part of Fapesp's fellow doctoral student Bruna Muys, showed that when overexpressed, miR-450a not only reduced the tumor but also blocked the metastasis process. However, it was still necessary to identify which genes were inhibited by the molecule.
“After the characterization phase, we needed to find out which cell migration and invasion genes miR-450a was regulating. With the technology that the NIH lab has in place to search for non-coding RNA targets, we found that this microRNA acts to reduce cell energy, causing it to die, ”said Silva Junior.
The discovery of the molecule and its mechanism came about as a result of Muys's master's project. The study, published in Plos One magazine in 2016, showed that high miR-450a expression occurs in the placenta and low tumor expression. The conclusion was that in the placenta the molecules would regulate mechanisms analogous to those of tumor development.
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