Deciphering RNA’s “second code”: a thesis from Cima University of Navarra studies new approaches to treating multiple myeloma

Despite advances in patients’ quality of life, multiple myeloma remains a hematologic disease for which new therapeutic strategies are still being researched due to frequent relapses. One of the main challenges in combating this hematologic disease is the wide variability among patients, as the information contained in their RNA molecules is so diverse that it is very difficult to predict how each person will respond to treatment.

Estíbaliz Urizar Compains (Pamplona, age 27) holds a bachelor’s degree in Biochemistry (2021) and a master’s degree in Master's Degree in research Biomédica (2022) from the School of Science University of Navarra. Under the supervision of Drs. Xabier Agirre Ena and Edurne San José Enériz, her master’s thesis in “ research ” focused on studying how a molecular “second code”—epitranscriptomics—regulates RNA.

RNA acts as a messenger that translates the instructions contained in DNA so that cells can function. “If we imagine RNA as a written text, epitranscriptomics would be the spelling: the accents and score that completely change the meaning of a sentence,” explains Urizar. However, while in healthy cells these modifications help them respond to the environment,“in cancer, the ‘spelling’ gets out of control and financial aid the tumor to grow,”he adds.

One of the main findings of the thesis is the demonstration that epitranscriptomics is hyperactive in multiple myeloma and that its excess reduces survival. Furthermore, the study identifies a gene— core topic, or VIRMA—as an essential driver of malignant cells: it provides them with energy, accelerates their division, and prevents them from dying. Based on this finding, the researcher has developed a therapeutic strategy targeting this gene, which has been shown to significantly reduce tumor growth in both in vitro and in vivo models.

research has also found evidence that epitranscriptomic alterations may appear in the early, benign stages of the disease. “Detecting these changes early would allow for intervention before the cancer fully develops, dramatically increasing the response to treatment and the likelihood of a cure,” says Urizar.

The next step will be to refine the delivery system for the treatment so that it targets only cancer cells while sparing healthy ones. To achieve this, it will be necessary to “minimize toxicity and optimize the dose so that this finding can make the leap from the laboratory to clinical trials with patients,” he concludes.
 

Bibliographical references

· Rafae A, van Rhee F, Al Hadidi S. Perspectives on the Treatment of Multiple Myeloma. Blood Cancer Discov. 2024;29(3):200–12. doi:10.1093/oncolo/oyad306.

· Heider M, Nickel K, Högner M, Bassermann F. Multiple Myeloma: Molecular Pathogenesis and Disease Evolution. Oncol Res Treat. 2021;44(12):672–81. doi:10.1159/000520312.

· Murakami S, Jaffrey SR. Hidden codes in mRNA: Control of gene expression by m6A. Mol Cell. June 16, 2022;82(12):2236–51. doi:10.1016/j.molcel.2022.05.029.

· Wang J, Zuo Y, Lv C, Zhou M, Wan Y. N6-methyladenosine regulators are potential prognostic biomarkers for multiple myeloma. IUBMB Life. 2023;75(2):137–48. doi:10.1002/iub.2678.