Peer Review #2 of "Identification of exosomal miRNAs associated with the anthracycline-induced liver injury in postoperative breast cancer patients by small RNA sequencing (v0.1)" [peer_review]

2020 unpublished
. Anthracycline-induced liver injury (AILI) is one of the serious complications of anthracycline-based adjuvant chemotherapy for postoperative breast cancer patients . Exosomal miRNAs, as signaling molecules in intercellular communication, play the essential roles in drug-induced liver injury (DILI). However, the expression profiles of them in patients with AILI remains unknown. Methods . Seven post-chemotherapy patients were recruited in this study. After isolated plasma-derived exosomes,
more » ... ived exosomes, small RNA sequencing revealed exosomal miRNA profiles and differentially expressed miRNAs (DE-miRNAs) were identified between the liver injury group and non-liver injury group. miRTarBase and miRDB were used to predict the potential target genes of DE-miRNAs. DILI-related genes were downloaded from the CTD Database. The intersection of predicted genes and DILI-related genes were identified as the AILI-related target genes of the DE-miRNAs. GO annotation and KEGG pathway enrichment analysis were performed by the DAVID database. Furthermore, the protein-protein interaction (PPI) network was established by STRING database and essential exosomal miRNAs were identified via Cytoscape software. Results. A total of 30 DE-miRNAs and 79 AILI-related target genes were identified. AILI-related target genes of the DE-miRNAs are significantly enriched in NOD-like receptor signaling pathway, HIF-1 signaling pathway and FoxO signaling pathway. Then, the hub genes were screened and we discovered that IL-6 and SOD2 are the most critical genes that may be involved in the development of AILI through the activation of immune response and the occurrence of oxidative stress, respectively. In addition, we found that miR-1-3p could potentially regulate most of the hub genes in the miRNA-hub gene network. Conclusion. We explored the potential functions of DE-miRNAs and suggested exosomal miR-1-3p might be the essential exosomal miRNA in the pathogenesis of AILI. Moreover, our study provided an experimental basis for experimental verification to reveal the actual function and mechanism of miRNAs in AILI. PeerJ reviewing PDF | Abstract 35 Background. Anthracycline-induced liver injury (AILI) is one of the serious complications of 36 anthracycline-based adjuvant chemotherapy for postoperative breast cancer patients. Exosomal 37 miRNAs, as signaling molecules in intercellular communication, play the essential roles in drug-38 induced liver injury (DILI). However, the expression profiles of them in patients with AILI 39 remains unknown. 40 Methods. Seven post-chemotherapy patients were recruited in this study. After isolated plasma-41 derived exosomes, small RNA sequencing revealed exosomal miRNA profiles and differentially 42 expressed miRNAs (DE-miRNAs) were identified between the liver injury group and non-liver 43 injury group. miRTarBase and miRDB were used to predict the potential target genes of DE-44 miRNAs. DILI-related genes were downloaded from the CTD Database. The intersection of 45 predicted genes and DILI-related genes were identified as the AILI-related target genes of the 46 DE-miRNAs. GO annotation and KEGG pathway enrichment analysis were performed by the 47 DAVID database. Furthermore, the protein-protein interaction (PPI) network was established by 48 STRING database and essential exosomal miRNAs were identified via Cytoscape software. 49 Results. A total of 30 DE-miRNAs and 79 AILI-related target genes were identified. AILI-50 related target genes of the DE-miRNAs are significantly enriched in NOD-like receptor signaling 51 pathway, HIF-1 signaling pathway and FoxO signaling pathway. Then, the hub genes were 52 screened and we discovered that IL-6 and SOD2 are the most critical genes that may be involved 53 in the development of AILI through the activation of immune response and the occurrence of 54 oxidative stress, respectively. In addition, we found that miR-1-3p could potentially regulate 55 most of the hub genes in the miRNA-hub gene network. 56 Conclusion. We explored the potential functions of DE-miRNAs and suggested exosomal miR-57 1-3p might be the essential exosomal miRNA in the pathogenesis of AILI. Moreover, our study 58 provided an experimental basis for experimental verification to reveal the actual function and 59 mechanism of miRNAs in AILI. 60
doi:10.7287/peerj.9021v0.1/reviews/2 fatcat:oybs2colbbfavnl2j5i7ondxsy