A microRNA suppressor will stop metastases
How to "turn off" cancer metastases?Elena Novoselova, STRF
Recently, there is more and more information about the role of miRNAs in the spread of metastases in the body.
Despite its potential as targets for combating metastatic processes, so far it has been possible to "silence" only microRNAs in normal, non-carcinogenic rodent and primate cells in tissue culture.
Scientists from the Massachusetts Institute of Technology (Massachusetts Institute of Technology, USA) have demonstrated the possibility of breast tumor therapy using a specific MIR-10b microRNA suppressor that suppresses the spread of metastases.
microRNAs are non–coding RNAs of 20-22 nucleotides in size. Their function is to regulate gene expression and, as a consequence, many protein synthesis processes. The targets of microRNAs are an impressive number of genes – at least a third of the entire genome. microRNA "turns off" protein synthesis by binding to the gene's matrix RNA, thereby triggering a cascade of processes that eventually lead to mRNA degradation.
Recently, there has been evidence that miR-10b microRNA is actively expressed in dividing metastasis cells under the influence of the Twist transcription factor, which regulates epithelial-mesenchymal transitions in carcinoma cells.
As a suppressor of miR-10b, experts from the Massachusetts Institute of Technology proposed using antagomers – chemically modified antisense oligonucleotides to the corresponding micro-RNAs. In this work, both in vitro and in vivo experiments, the use of miR-10b antagomir significantly reduced the microRNA concentration and increased the level of Hoxd10 protein contained in the cell, the matrix RNA of which is the "target" for miR-10b.
Proteins encoded by genes of the Hox family regulate the processes of embryonic development of organisms. But some of them are also involved in the processes of carcinogenesis. Hoxd10 can block the expression of the RHOC gene, which is necessary for tumor cells to move and embed into other tissues, thereby preventing the process of metastasis. And the higher the concentration of Hoxd10, the more effectively the growth of metastases is restrained.
Antagomirs were administered intravenously to model mice, but this compound does not overcome the blood-brain barrier, which makes its use safer. The inhibitory effect against miR-10b was observed for three weeks after a single injection. Regulation of miR-10b levels using antagomers in model animals with significantly spread metastases did not reduce the size of the primary tumor, but inhibited further metastasis and penetration of the tumor into the lungs, which usually accompanies breast cancer.
Ninety percent of cancer deaths are caused by the spread of primary tumor metastases. Surgical intervention, radiation therapy and chemotherapy are able to effectively control the growth of the primary tumor, but the possibilities of modern medicine for inhibiting metastasis processes are limited. In this regard, the selectivity of the action of antagomers against a certain microRNA and the prolongation of the therapeutic effect makes it possible to designate this class of compounds as potential therapeutic agents for the treatment of oncological diseases. The further work of specialists from the Massachusetts Institute of Technology is aimed at creating preventive means against metastasis, which can be combined with surgical methods to prevent the recurrence of the tumor and its spread throughout the body.
The results of the work are published in the journal Nature Biotechnology (Li Ma et al., Therapeutic silencing of miR-10b inhibits metastasis in a mouse mammary tumor model).
Portal "Eternal youth" http://vechnayamolodost.ru30.03.2010