Editorial

Di Leva, Gianpiero; Croce, Carlo Maria

Abstract

After their discovery in mammalians, more than 20,000 publications about microRNAs have been recorded in Pubmed over the last 11 years. Although some aspects of their biology are still unknown and need some clarifications, it is now clear that microRNAs, by regulating almost all molecular signaling that control cell proliferation, apoptosis, stress response, migration and differentiation, exert a fundamental role in all aspects of human diseases, including cancer. MicroRNAs are small non-coding RNAs of 18–25 nucleotides in length that post-transcriptionally suppress gene expression by translational inhibition or mRNA degradation [1]. Large bioinformatic screening demonstrated that 3% of the human genome codes for microRNAs and over 30% of the transcriptome is under their post-translational control. The initial indication that miRNAs play important roles in human disease came from the pivotal studies on let-7 and lin-4 in Caenorhabditis elegans [2]. Loss of these two miRNAs evokes characteristics of human malignant cells, such as continuous proliferation in adult tissues, loss of differentiation and reduced cell death. Today, we can state with confidence, based on hundreds of expression profiling studies, that tumors ubiquitously exhibit dysregulated microRNA expression relative to the corresponding normal tissues [3]. MicroRNA expression signatures allow different types of cancer to be discriminated with high accuracy [4], [5] and the tissue of origin of poorly differentiated tumors to be identified. The potential value of miRNAs as prognostic and predictive biomarkers in cancer is elegantly highlighted by the recent work of Volinia and Croce where miRNA expression patterns of invasive ductal carcinoma are identified in a test cohort of 466 patients and then validated in eight other different breast cancer cohorts comprising a total of 2399 patients [6]. Thirty mRNAs and seven microRNAs, including miR-103, -484, and -874 were associated with the overall survival across the different clinical and molecular subclasses of breast cancer. This global signature showed a better risk stratification compared to other predictors including the already used Mammaprint or Oncotype DX. Although this study and others highlight the potential of miRNA profiling for defining prognosis, stratifying risk, and identifying low- and high-risk populations of patients with cancer, the biggest challenge ahead is to assess real clinical utility of microRNas by planning appropriately designed and powered prospective blinded and randomized clinical trials, and subsequently validated in follow-up trials.

Citation

Di Leva, G., & Croce, C. M. (2013). Editorial. Clinical Biochemistry, 46(10-11), 840-841. https://doi.org/10.1016/j.clinbiochem.2013.05.060

• Journal Article Type: Article
• Acceptance Date: May 3, 2013
• Online Publication Date: May 31, 2013
• Publication Date: 2013-07
• Deposit Date: Jun 12, 2023
• Journal: Clinical Biochemistry
• Print ISSN: 0009-9120
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 46
• Issue: 10-11
• Pages: 840-841
• DOI: https://doi.org/10.1016/j.clinbiochem.2013.05.060
• Keywords: Clinical Biochemistry; General Medicine