Project description:Exposure to high-dose radiation causes life-threatening serious intestinal damage. Histological analysis is the most accurate method for judging the extent of intestinal damage after death. However, it is difficult to predict the extent of intestinal damage to body samples. Here we focused on extracellular microRNAs (miRNAs) released from cells and investigated miRNA species that increased or decreased in serum and feces using a radiation-induced intestinal injury mouse model. A peak of small RNA of 25–200 nucleotides was detected in mouse serum and feces 72 h after radiation exposure, and miRNA presence in serum and feces was inferred. MiRNAs expressed in the small intestine and were increased by more than 2.0-fold in serum or feces following a 10 Gy radiation exposure were detected by microarray analysis and were 4 in serum and 19 in feces. In this study, miR-375-3p, detected in serum and feces, was identified as the strongest candidate for a high-dose radiation biomarker in serum and/or feces using a radiation-induced intestinal injury model.
Project description:Previously, we used mouse and non-human primate models to show that serum miRNAs may predict the biological impact of lethal and sublethal radiation doses. We hypothesized that these results can be replicated in humans treated with total body irradiation (TBI), and that miRNAs may be used as clinically feasible biodosimeters. To test this hypothesis, serial serum samples were obtained from 25 patients who underwent allogeneic stem-cell transplantation and profiled for miRNA expression using next-generation sequencing. Differential expression results were largely consistent with previous studies and allowed us to select miRNAs, including miR-150-5p, miR-126-5p, miR-375, miR-215-5p, miR-144-5p, miR-122-5p, miR-320d and miR-10b-5p to build classifiers using qPCR-based quantification. We therefore conclude that serum miRNAs reflect radiation exposure and dose for humans undergoing TBI and may be used as functional biodosimeters for precise identification of people exposed to clinically significant radiation doses.
Project description:Biomarkers of tumour response to radiotherapy could help in optimising cancer treatment. In this study, we focus on identifying changes in extracellular miRNA as a biomarker of radiation-induced damage to human colorectal cancer cells. HCT116 cells were exposed to increasing doses of X-rays, and extracellular miRNAs were analysed by microarray. The results were correlated with frequencies of micronuclei. Fifty-nine miRNAs with positive correlation and four with negative correlation between dose (up to 6 Gy) and expression of extracellular miRNA were verified. In addition, for samples between 0 and 10 Gy, 12 miRNAs into those 59 miRNAs with positive correlation were verified. Of these, these miRNAs showed significantly positive correlation up to 10 Gy between micronucleus frequency and expression of extracellular miRNA. These results suggest that specific miRNAs could be cell damage markers and could serve as secreted radiotherapy response biomarkers for colorectal cancer; however, the results must be validated in serum samples collected from patients undergoing radiotherapy.
Project description:Exposure to high-doses of ionizing radiation (IR) leads to development of a strong acute radiation syndrome (ARS) in mammals. ARS manifests after a latency period and it is important to develop fast prognostic biomarkers for its early detection and assessment. Analysis of chromosomal aberrations in peripheral blood lymphocytes is the gold standard of biological dosimetry, but it fails after high doses of IR. Therefore, it is important to establish novel biomarkers of exposure that are fast and reliable also in the high dose range. Here, we investigated the applicability of miRNA levels in mouse serum.
Project description:Exposure to high-dose radiation causes life-threatening intestinal damage. Histopathology is the most accurate method of judging the extent of intestinal damage following death. However, it is difficult to predict the extent of intestinal damage. The present study investigated extracellular microRNAs (miRNAs or miRs) in serum and feces using a radiation-induced intestinal injury mouse model. A peak of 25-200 nucleotide small RNAs was detected in mouse serum and feces by bioanalyzer, indicating the presence of miRNAs. Microarray analysis detected four miRNAs expressed in the small intestine and increased by >2-fold in serum and 19 in feces following 10 Gy radiation exposure. Increased miR-375-3p in both serum and feces suggests leakage due to radiation-induced intestinal injury and may be a candidate for high-dose radiation biomarkers.
Project description:Osteoblast is one of the bone marrow cells and not only play a central role in bone turnover, but also play a role as supporting cell for hematopoietic stem/progenitor cells. In the field of radiotherapy, internal radiotherapy using radioactive isotopes that emit alpha particles is performed, and antitumor effect is expected by radioisotopes (such as 223-Ra) when the primary cancer cells metastasize to bone marrow. In general, higher dose rates of ionising radiation can induce cell death through DNA damage. However, the extent of DNA damage and repair (radiosensitivity) varies between tissue cell types. In the bone marrow environment, there are many unknowns regarding the radiosensitivity and the its related gene expression in osteoblast, especially the expression status of micro RNAs (miRNAs). The purpose of this study is to reveal the expression pattern of miRNAs in osteoblasts exposed to alpha particle radiation and to identify miRNAs associated with radiosensitivity. Osteoblastic cell line, MC3T3-E1 cell was exposed to 0.223 Gy/min alpha particles (total dose: 0.5 Gy and 1 Gy) and extracted total RNAs after the incubation of 24 h. A significantly up- or down-regulated 21 miRNAs were observed in comparison to non-irradiated control. Using omicsnet data analysis system, we focused on 5 miRNAs (miR-467f, miR-362-3p, miR-5119, miR-292a-5p, miR-466h-3p) and validated them using RT-qPCR. As a result, A higher expression of miR-362-3p after exposure of alpha particle irradiation was reproducibly observed. These results suggested that osteoblastic cell irradiated to alpha particle radiation has a unique miRNA expression pattern.
Project description:The effects of different diets on bovine serum extracellular vesicle (EV)-miRNAs are explored by small RNA Solexa sequencing. We partly replaced alfalfa hay with whole cotton seed and soybean hull in the feed formula of treat cows. Small RNAs are enriched in bovine serum EVs, including miRNAs, snRNAs, tiRNAs, Cis-regulatory elements, piRNAs, etc. Totally 359 bos taurus miRNAs are identified by sequencing. There are 15 immune-related miRNAs in the top 20 serum EV-miRNAs, accounting for about 80% of the total. Seven differently expressed known miRNAs were detected in responding to different diets. KEGG analysis showed differently expressed miRNAs are related to hormone signal pathways and protein metabolism.