Importance of fundamental science as the cornerstone for translational research
Research headlines that attract the most publicity are those that show success in benefitting patients, whether it is through new targeted drugs or new immunotherapies. Many funding bodies and charities have also changed their policy toward funding more translational research that has clear economic, clinical and patient benefit. We must remember, however, that the innovations for these transformative publications and translational research projects are imbedded in our fundamental understanding of the molecular and cellular biology of disease investigated at the basic science level. These investigations are the cornerstone of translational research.
The BJUI has continued its tradition of publishing fundamental research with translational insight, and this is exemplified in this month’s article by Liu et al. [1], which undertakes to explain the mechanistic and functional role of EZH2 in RCC. In this study the authors manipulate the expression of EZH2 by silencing it using short-hairpin EZH2, which targets the RNA. They also use a small molecule inhibitor of methyltransferase which has been shown to deplete the expression of EZH2. Both these approaches inhibit EZH2 expression, which was associated with reduced migration and invasion of the cancer cells, as assessed in in vitro models, as well as with slowing tumour growth and prolonging survival in an in vivo nude mouse model. These changes were mechanistically explained by a change in the mesenchymal epithelial transition phenotype of the tumour cells. The authors then went on to show that EZH2 is associated with E-cadherin suppression and poor survival in patients with RCC, demonstrating the translational importance of these findings.
This impo rtant fundamental and translational paper adds to the growing body of evidence that EZH2, which is a histone methyltransferase and regulator of gene expression, plays a key role in the development of a range of cancers including prostate, breast, lymphoma and colon [2].
The Translational Science section of the BJUI is looking for relevant and citable articles similar to the paper by Liu et al., which are imbedded in fundamental science and bring the concept into clinical investigation, either through its validation in clinical material or manipulation in clinically relevant in vivo model systems, and represent a clear translational step.
To facilitate our readers’ understanding and to familiarize them with often complicated and complex fundamental scientific concepts, in 2013 the BJUI introduced the ‘Science Made Simple’ review-type article section, in which various scientific concepts are explained so as to assist interactions between scientists and clinicians as they translate their ideas and findings into clinical utility.
References
1 Liu L, Xu Z, Zhong L et al. Enhancer of zeste homolog 2 (EZH2) promotes tumour cell migration and invasion via epigenetic repression of E-cadherin in renal cell carcinoma. BJU Int 2016; 117: 351–62
2 Simon JA, Lange CA. Roles of the EZH2 histone methyltransferase in cancer epigenetics. Mutat Res 2008; 647: 21–9
, BJUI Consulting Editor, Translational Science
UCD School of Medicine and Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland
