Iranian scientists from the Royan Institute, in collaboration with researchers from the University of Duisburg-Essen in Germany, have created the namiRa database, which translates from Persian as 'immortal.' This specialized and comprehensive database represents a valuable scientific infrastructure that aids in identifying new cancer biomarkers, accelerating the search for therapeutic targets, and supporting future research in oncology.
NamiRa was compiled by systematically selecting and integrating data from nearly 10,000 scientific publications. By consolidating experimentally validated information on microRNAs associated with cancer, it has become one of the most complete global resources for studying the functions of microRNAs in human cancer and, according to Royan.org, is expected to accelerate research in this field, as well as the discovery of biomarkers and the development of innovative diagnostic and therapeutic strategies.
According to the press service of the Royan Institute, microRNAs are small non-coding regulatory RNA molecules that regulate gene expression and play a key role in numerous biological processes, including cell proliferation, differentiation, migration, survival, and apoptosis. Dysfunctional and altered microRNA expression is linked to the initiation and development of many human malignant neoplasms, making these molecules a central focus of modern research in oncology and precision medicine.
As part of this joint project, Dr. Sharif Moradi and his colleagues from the Royan Institute, along with scientists from the University of Duisburg-Essen, developed namiRa. This manually curated database provides researchers with integrated, structured, and experimentally verified information on microRNA expression profiles, their functional roles, detection methods, confirmed target genes, and regulatory networks across a wide spectrum of human cancer types.
To create the database, the team conducted a systematic literature review, followed by meticulous manual curation of 9,983 relevant scientific publications. This allowed them to extract, classify, and consolidate experimentally validated data describing the link between 1,095 human microRNAs and 33 different types of human cancer. As a result, namiRa has become one of the most comprehensive specialized resources currently available for studying microRNA-cancer relationships.
Unlike many existing databases that only provide basic expression profiles or information on microRNA-target associations, namiRa integrates multiple levels of experimentally validated evidence. This evidence includes microRNA expression patterns, detection methods, functional characterization obtained from both in vitro and in vivo studies, confirmed target genes, and interactive visualization of microRNA regulatory networks. This comprehensive structure gives researchers a deep understanding of the role of microRNAs in cancer initiation, progression, and metastasis, while also facilitating comparative analysis between different tumor types.
By transforming disparate experimental results into a single high-quality reference resource, the database promotes the advancement of data-driven biomedical research and advances the application of new computational technologies in precision medicine. The study describing namiRa was published in the international peer-reviewed journal Computers in Biology and Medicine (Elsevier), a leading publication in the fields of computational medicine and biomedical informatics.
Researchers have created an innovative strategy to combat cancer by employing an enzyme from the CRISPR system. This enzyme has the ability to destroy the DNA of tumor cells and force them to self-destruct.
The methodology, detailed in two articles published in the journal Nature, utilizes an enzyme that can be programmed to recognize a specific messenger RNA, such as one generated by a malignant cell. Upon locating this RNA, the enzyme fragments the entire cell genome. Scientists point out that this technique could constitute a new pathway to eradicate cells producing mutant proteins classified as unreachable by conventional drugs.
Yang Liu, a molecular biologist from the University of Utah School of Medicine in Salt Lake City (USA) and author of one of the studies, described the process as a 'molecular death switch that recognizes a specific RNA,' characterizing it as 'programmable chemotherapy.' The technology has already been applied in the development of an experimental treatment against head and neck cancers linked to human papillomavirus (HPV). This project is being led by Akribion Therapeutics, a biotechnology company based in Zwingenberg (Germany).
Paul Scholz, co-founder and R&D director at Akribion, predicts that the first results from clinical trials may be achieved by 2030. CRISPR systems are naturally found in bacteria and other microorganisms, functioning as an immune defense mechanism. They use RNA molecules to guide enzymes called Cas to the DNA of invaders, allowing for the cutting and destruction of this genetic material. Over ten years ago, scientists adapted this mechanism for gene editing, creating guide RNAs to direct Cas enzymes to specific locations in the genome.
About a decade ago, Ryan Jackson, a biochemist at Utah State University in Logan (USA), began studying the Cas12a2 protein. Initially, researchers expected it to behave like other gene-editing enzymes, but the results did not match predictions. Jackson reported accusing his students of contamination. Subsequently, his team and another group discovered that Cas12a2 exhibited distinct behavior: after recognizing an RNA sequence corresponding to its guide RNA, the enzyme began indiscriminately destroying the cell's DNA, halting its growth. In nature, this mechanism helps prevent the spread of infections between bacteria.
The two teams involved in the studies adapted this mechanism to attack tumors caused by difficult-to-treat genetic mutations. One group programmed Cas12a2 to identify RNA produced by cells with mutations in the TP53 gene, which is affected in almost half of all cancer cases. The other directed the enzyme against RNA derived from a mutated version of the KRAS gene, whose altered proteins promote uncontrolled cell growth in some of the most aggressive cancers. In both studies, Cas12a2 showed high precision in eliminating only the cells carrying the mutations, even when the difference from normal RNA was only a single letter. Tests were conducted in human cells cultured in the laboratory and in mice, where the technique reduced tumors related to mutated TP53 and also those caused by HPV.
Baojun Wang, a synthetic biologist from Zhejiang University in Hangzhou (China), emphasizes that there is still a long way between current experiments and a therapy available for humans, although he considers the work a 'remarkable' proof of concept for a promising technology. According to Yang Liu, the potential of Cas12a2 extends beyond tumors, potentially being applied in autoimmune and neurological diseases in the future, provided they are linked to the production of a specific RNA. Jingkun Zeng, a cancer biologist at the Gladstone Institutes in San Francisco, California (USA), and co-author of the TP53 study, believes that the technology will offer a great advantage over traditional chemotherapies because Cas12a2 acts only on cells with the target RNA, unlike many current treatments that attack rapidly dividing cells indiscriminately.
Despite the advances, researchers identify crucial obstacles for clinical application. One challenge is getting Cas12a2 inside the cells, as it is a relatively large protein. It is also necessary to confirm that it does not harm healthy cells. Although the experiments show high specificity, eliminating only cells with mutant RNA, Rene Bernards, a cancer geneticist at the Netherlands Cancer Institute in Amsterdam (Netherlands), considered the result 'somewhat disappointing' because it did not eliminate all cancer cells, not even in lab culture. However, he assesses that a Cas12a2-based therapy could be used in combination with other oncological treatments to increase efficacy and reduce the risk of tumor resistance, concluding that the technology still holds great potential and requires refinement.
