The previously unchartered gene expression territory governed by circular RNAs is becoming clearer with the onset of deeper sequencing technologies. The translation of circular RNAs remained a controversial theory until earlier this year, when two studies [1, 2] showed endogenous circular RNA translation in vitro and in vivo, and have further provided mechanistical evidence. In this edition of Oncogene, Zhang et al., provide evidence for the first circular RNA translated with relevance to cancer; a novel tumour suppressor protein, SHPRH-146aa, produced by circ-SHPRH driven by IRES elements. The novel tumour suppressor protein produced by the circular RNA was found to work in synergy with the full-length protein, behaving as a protective decoy molecule to decrease degradation, and thus increasing the tumour suppressive functionality of the gene. An extended patient survival time was seen in glioblastoma patients with elevated levels of SHPRH-146aa. This study also marks the discovery of the first circular RNA with an overlapping initiation and termination codon, resulting in the translation of the full circRNA, exploring a mechanism not previously found or seen.

Functional changes in the heart in patients with cancer can be a result of both the disease itself and various cancer therapies, and limiting cardiac damage has become an increasingly important issue as survival rates in patients with cancer have improved. Processes involved in cancer-induced cardiac atrophy may include cardiomyocyte atrophy and apoptosis, decreased protein synthesis, increased autophagy and proteolysis via the ubiquitin-proteosome system. Further to direct effects of malignancy on the heart, several chemotherapeutic agents are known to affect the myocardium, in particular the anthracyclines. The aim of this report is to review the effects of cancer and cancer treatment on the heart and what is known about the underlying mechanisms. Furthermore, clinical strategies to limit and treat cancer-associated cardiac atrophy are discussed, emphasising the benefit of a multidisciplinary approach by cardiologists and oncologists to optimise models of care to improve outcomes for patients with cancer.

et al. (2020) SCIRT lncRNA restrains tumorigenesis by opposing transcriptional programs of tumor-initiating cells. Cancer Research.

In human, mutations of the protocadherins FAT4 and DCHS1 result in Van Maldergem syndrome, which is characterised, in part, by craniofacial abnormalities. Here, we analyse the role of Dchs1-Fat4 signalling during osteoblast differentiation in mouse. We show that Fat4 and Dchs1 mutants mimic the craniofacial phenotype of the human syndrome and that Dchs1-Fat4 signalling is essential for osteoblast differentiation. In Dchs1/Fat4 mutants, proliferation of osteoprogenitors is increased and osteoblast differentiation is delayed. We show that loss of Dchs1-Fat4 signalling is linked to increased Yap-Tead activity and that Yap is expressed and required for proliferation in osteoprogenitors. In contrast, Taz is expressed in more-committed Runx2-expressing osteoblasts, Taz does not regulate osteoblast proliferation and Taz-Tead activity is unaffected in Dchs1/Fat4 mutants. Finally, we show that Yap and Taz differentially regulate the transcriptional activity of Runx2, and that the activity of Yap-Runx2 and Taz-Runx2 complexes is altered in Dchs1/Fat4 mutant osteoblasts. In conclusion, these data identify Dchs1-Fat4 as a signalling pathway in osteoblast differentiation, reveal its crucial role within the early Runx2 progenitors, and identify distinct requirements for Yap and Taz during osteoblast differentiation.