Clinical Impact and Regulation of the circCAMSAP1/ miR-328-5p/E2F1 Axis in Colorectal Cancer
Authors: Ion Cristóbal, Melani Luque, Marta Sanz-Alvarez, Federico Rojo, Jesús García-Foncillas
Journal: Molecular Therapy (2020)

The recent work by Zhou et al.1Zhou C. Liu H.S. Wang F.W. Hu T. Liang Z.X. Lan N. He X.W. Zheng X.B. Wu X.J. Xie D. et al.circCAMSAP1 Promotes Tumor Growth in Colorectal Cancer via the miR-328-5p/E2F1 Axis.Mol. Ther. 2020; 28: 914-928Abstract Full Text Full Text PDF PubMed Scopus (75) Google Scholar provides new findings about the functional and clinical impact of the circular RNA (circRNA) circCAMSAP1 in colorectal cancer (CRC). Of relevance, the level of expression of this circRNA showed diagnostic and prognostic value in CRC patients. The authors reported that circCAMSAP1 biogenesis was mediated by the splicing factor epithelial-splicing regulatory protein 1 (ESRP1). Mechanistically, circCAMSAP1 acted as a sponge for miR-328-5p, thereby inhibiting the miR-328-5p-induced suppression of the transcription factor E2F1. Finally, circCAMSAP1 knockdown reduced cell proliferation in vitro and tumor growth in vivo via E2F1 modulation. These interesting results highlight that the circCAMSAP1/miR-328-5p axis represents a potential target with promising clinical relevance in CRC. However, there are some additional considerations that should be taken into account. circCAMSAP1 was found to be overexpressed in CRC tissues, and its expression correlated with poor outcome. After performing a multivariate analysis, the authors suggested that circCAMSAP1 represents an independent prognostic factor. From our point of view, multivariate analyses must include all the significant variables obtained in univariate analyses. Thus, the authors should have included E2F1, since they showed that it strongly correlated with circCAMSAP1 expression and also predicted poor outcome in the same patient cohort with even more significance than circCAMSAP1. Therefore, it remains unclear whether circCAMSAP1 is truly an independent prognostic factor or whether its prognostic value is dependent upon E2F1 expression. In addition, circCAMSAP1 was proposed to represent a potential diagnostic marker since its expression was found to be greater in the serum of CRC patients prior to surgery than in patients after surgery or in normal controls. However, the low number of patients studied (n = 20) is a relevant limitation and these results have to be interpreted with caution before further validation in larger independent CRC patient cohorts. Another important issue in order to strengthen the clinical usefulness of circCAMSAP1 as a biomarker would be to determine whether serum levels of this circRNA could serve as a prognostic biomarker in liquid biopsies prior to surgery, as was observed by Zhou et al.1Zhou C. Liu H.S. Wang F.W. Hu T. Liang Z.X. Lan N. He X.W. Zheng X.B. Wu X.J. Xie D. et al.circCAMSAP1 Promotes Tumor Growth in Colorectal Cancer via the miR-328-5p/E2F1 Axis.Mol. Ther. 2020; 28: 914-928Abstract Full Text Full Text PDF PubMed Scopus (75) Google Scholar in CRC tissues. It would be also interesting to evaluate the expression of circCAMSAP1 after surgery to evaluate its potential predictive value in anticipating relapses. Furthermore, several lines of evidence highlight the potential of other circRNAs described by the authors to be deregulated in CRC. A recently published study has shown that circPVT1 sponges miR-205-5p,2Liu Y.P. Wan J. Long F. Tian J. Zhang C. circPVT1 Facilitates Invasion and Metastasis by Regulating miR-205-5p/c-FLIP Axis in Osteosarcoma.Cancer Manag. Res. 2020; 12: 1229-1240Crossref PubMed Scopus (26) Google Scholar which is known to target E2F1.3Noguchi S. Iwasaki J. Kumazaki M. Mori T. Maruo K. Sakai H. Yamada N. Shimada K. Naoe T. Kitade Y. Akao Y. Chemically modified synthetic microRNA-205 inhibits the growth of melanoma cells in vitro and in vivo.Mol. 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Commun. 2019; 512: 716-722Crossref PubMed Scopus (67) Google Scholar it would be very interesting to analyze the potential role of this circRNA in regulating ESRP1 expression and, indirectly, the circCAMSAP1/miR-328-5p/E2F1 axis in CRC. The authors have declared no conflicts of interest. This work was supported by PI18/00382 and PI16/01468 grants from "Instituto de Salud Carlos III FEDER."