Serum miR-375-3p increase in mice exposed to a high dose of ionizing radiation

Abstract

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. We found significantly increased levels of miR-375-3p following whole body exposure to 7 Gy of X-rays. In addition, we analyzed their levels in various organs of control mice and found them to be especially abundant in the pancreas and the intestine. Following a dose of 7 Gy, extensive cell death occurred in these tissues and this correlated negatively with the levels of miR-375-3p in the organs. We conclude that high expressing tissues of miR-375-3p may secrete this miRNA in serum following exposure to 7 Gy. Therefore, elevated miR-375-3p in serum may be a predictor of tissue damage induced by exposure to a high radiation dose.

HER2‑positive breast cancer that resists therapeutic drugs and ionizing radiation releases sphingomyelin‑based molecules to circulating blood serum

“…Thus, their expression relates to cancer tissue growth or distant metastasis. We have previously reported that during the active release of EVs to blood flow after exposure to higher dose of ionizing radiation, the lower accumulation of EV components in their original tissue cells was observed in comparison to the other tissues with non-active release of EVs (27,28). Our case data showed that the concentration of nSMase co-expressed with HER2 in 1st recurrent cancer tissue, where the levels of both are lower than in primary cancer tissue (Fig.…”

“…These responses suggested that recurrent cancer tissues more easily release EVs to peripheral blood serum and promote cancer progression and expansion. Thus, one reported mechanism is the transfer of miRNAs via exosomes from cancer cells to microenvironmental cells, promoting angiogenesis (28,29).…”

Injured pancreatic β cells enhance the release of miR‑375‑3p into the extracellular space

“…We have previously shown that miR-375-3p increases in the serum of mice exposed to 7 Gy X-rays causing cytotoxicity in pancreatic β cells (2). However, the direct relationship between miR-375-3p level increases in the blood and the cytotoxicity caused by 7 Gy irradiation remained to be clarified.…”

“…MicroRNAs (miRNAs) are small (18-25 nucleotides) non-coding RNA harboring a post-transcriptional gene regulatory function (1). Currently, miRNAs have been detected in various body fluids, including serum (2), plasma (3), urine (4), cerebrospinal fluid (5), breast milk (6), saliva (7), bronchoalveolar lavage fluid (8), ascites (9), and pleural effusion (10). Noteworthy, miRNAs are stable under non-physiological conditions, whether in body fluids or culture media.…”

Exosome-packaged miR-1246 contributes to bystander DNA damage by targeting LIG4

“…Chiba et al indicated that miR-375-3p is significantly increased following exposure to 7 Gy of IR, and the authors suggested that this miRNA can serve as a predictor of DNA damage induced by IR. 30 Interestingly, following secretion from targeted cells, miRNAs packaged in exosomes can move to a remote distance to influence cell functions and modify the niche and host reaction in targeted or nontargeted cells, which leads to the bystander effect. Our previous study indicated that miR-7-5p packaged in exosomes from 2-Gy-irradiated human bronchial epithelial BEP2D cells induced bystander autophagy in nonirradiated BEP2D cells, and this autophagy was associated with the EGFR/Akt/mTOR signalling pathway.…”