New therapies based on microRNAs could be key in more aggressive thyroid cancer

Researchers belonging to the CIBER Cancer Tumor Progression Program (CIBERONC), from the Pilar Santisteban group at the CSIC, have identified that the biogenesis of microRNAs plays a key role in the development of more aggressive thyroid cancer. In this way, the new advances in the field of thyroid cancer research show that this finding may be relevant for new therapeutic applications.

More specifically, the researchers of CIBERONC have shown that the levels of DICER, a fundamental protein for the biogenesis of microRNAs, are very low in thyroid cancer, which contributes to a greater aggressiveness, confirming that in this type of tumor it acts as a tumor suppressor. . In addition, this work describes new therapeutic applications based on the inhibition of an oncogenic microRNA and the restoration of the machinery of biogenesis that could serve as a treatment in this type of cancer.

Thus, in the words of the researcher of the CSIC Pilar Santisteban, "our results highlight a potential application of therapies based on microRNAs that include inhibitors of oncogenic microRNAs and drugs that allow the restoration of the machinery of biogenesis of microRNAs, for the treatment of thyroid cancer and other cancers. "

Implications

This work published in the Oncogene magazine , establishes that the DICER1 gene is target of the oncogenic microRNA miR-146b, which is the most over-expressed in thyroid cancer. Different functional assays have shown that this microRNA is responsible, at least in part, for the decrease of DICER1 in thyroid tumor cells, which promotes proliferation, migration, invasion and epithelial-mesenchymal transition, key characteristics for tumor transformation and aggressiveness.

The clinical application of this finding was demonstrated in two related preclinical studies. In the first, it was demonstrated that the systemic injection of an inhibitor of miR-146b in mice with orthotopic thyroid tumors significantly reduces tumor growth and increases DICER1 levels. Secondly, the administration of Enoxacin, a molecule that promotes the activity of DICER1, reduced the size of the thyroid tumor and its aggressiveness.

It should be remembered that thyroid cancer is the most frequent endocrine neoplasm and its incidence has increased the most in recent years. In general terms, it has a good prognosis given its response to treatment with radioactive iodine. However, there are a number of patients who do not respond to this treatment, so the search for new mechanisms that explain the formation and maintenance of this type of cancer is essential to obtain new molecular targets and new treatments.

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