Colorectal cancer (CRC) is one of the most common cancer types, ranking third after lung and breast cancers. As such, it demands special attention for better characterization, which may eventually result in the development of early detection strategies and preventive measures. Currently, components of bodily fluids, which may reflect various disease states, are being increasingly researched for their biomarker potential. One of these components is the circulating extracellular vesicles, namely, exosomes, which are demonstrated to carry various cargo. Of importance, the non-coding RNA cargo of circulating exosomes, especially long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and micro RNAs (miRNAs), may potentially serve as significant diagnostic and prognostic/predictive biomarkers. In this review, we present existing evidence on the diagnostic and prognostic/predictive biomarker value of exosomal non-coding RNAs in CRC. In addition, taking advantage of the miRNA sponging functionality of lncRNAs and circRNAs, we demonstrate an experimentally validated CRC exosomal non-coding RNA-regulated target gene axis benefiting from published miRNA sponging studies in CRC. Hence, we present a set of target genes and pathways downstream of the lncRNA/circRNA–miRNA–target axis along with associated significant Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, which may collectively serve to better characterize CRC and shed light on the significance of exosomal non-coding RNAs in CRC diagnosis and prognosis/prediction.
Breast cancer (BC) has recently become the most common cancer type worldwide, with metastatic disease being the main reason for disease mortality. This has brought about strategies for early detection, especially the utilization of minimally invasive biomarkers found in various bodily fluids. Exosomes have been proposed as novel extracellular vesicles, readily detectable in bodily fluids, secreted from BC-cells or BC-tumor microenvironment cells, and capable of conferring cellular signals over long distances via various cargo molecules. This cargo is composed of different biomolecules, among which are the novel non-coding genome products, such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and the recently discovered circular RNA (circRNA), all of which were found to be implicated in BC pathology. In this review, the diverse roles of the ncRNA cargo of BC-derived exosomes will be discussed, shedding light on their primarily oncogenic and additionally tumor suppressor roles at different levels of BC tumor progression, and drug sensitivity/resistance, along with presenting their diagnostic, prognostic, and predictive biomarker potential. Finally, benefiting from the miRNA sponging mechanism of action of lncRNAs and circRNAs, we established an experimentally validated breast cancer exosomal non-coding RNAs-regulated target gene axis from already published exosomal ncRNAs in BC. The resulting genes, pathways, gene ontology (GO) terms, and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis could be a starting point to better understand BC and may pave the way for the development of novel diagnostic and prognostic biomarkers and therapeutics.
Dr Hocking raises a number of important issues in commenting on our paper about mortality in the cohort of current and former employees of the Australian Nuclear Science and Technology Organisation (ANSTO) (Aust N Z J Public Health 2005;29(3): 229-37).Our paper was not intended to demonstrate or disprove the carcinogenicity of ionising radiation per se, but to compare the mortality of the ANSTO worker cohort with that of the New South Wales population. We agree that our study shares characteristics in common with many retrospective occupational cohort studies, including the absence of comprehensive information on a range of potentially important exposure variables and incomplete follow-up of some cohort members. We doubt that major methodological improvements could have been made to the study, given the small size of the cohort, the limited availability of exposure data for several potential carcinogens, both occupational and non-occupational, and the chronological period covered by computerised mortality registers.
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