Abstract
MiRNAs as tumor suppressor have been identified in variety of cancer, but the role of miRNAs involve in ARS (acute radiation syndrome) in Tibet minipig are poorly understood. Here, in order to study the relationship between miRNAs pattern and ARS, microarray chip technology was used for screening of ARS related miRNAs in Tibet minipig small intestine.Not castrated male Tibetan minipig were chose as animal model (n = 54), and exposed to the total body X-ray radiation at 0, 2, 5, 8, 11, 14 Gy (n= 9/ group), The total miRNA was extracted and hybridized to microarray chip. The HIC cell proliferation was evaluated by CCK8 assay, and the apoptosis was evaluated by flow-cytometric after X-ray irradiation. The athymic mice subcutaneous injection was used to research tumor formation. The bioinformatics tools and luciferase assay was applied to detect the relationship between miR-338-3p and its target. In total, 63 specific miRNAs were differentially regulated in the exposed small intestin tissues with 3, 24, 29, 25, and 32 miRNAs identified per dose-level (2, 5, 8, 11, and 14 Gy, respectively). MiR-338-3p was commonly regulated at 5, 8, 11, and 14 Gy dose levels and was used for cell assay. MiR-338-3p can regulates. HIC cell proliferation and apoptosis after X-ray irradiation administration. DYRK2 is one of target of miR-338-3p and suppressed by X-ray irradiation administration. Our study first revealed the ARS associated miRNA signatures were generally dose-specific, and miR-338-3p involve in response to ARS by targeting DYRK2 and may be used as early immunological response biomarker for ARS research.
Summary statement In summary, our studies show that the miRNA signatures were in general X-ray irradiation dose-specific, and miR-338-3p can suppress HIC cell proliferation and induce HIC cell apoptosis by regulating the expression level of DYRK2 partially, which may be used as early immunological response biomarker for ARS in clinical research. However, more research is needed to evaluate the role of these and other miRNAs in small intestin in response to radiation administration.