Discovery and characterization of miRNAs in mouse thymus responses to ionizing radiation by deep sequencing

Abstract

To investigate the potential regulatory roles of microRNA (miRNA) in mouse response to ionizing radiation (IR)-induced thymus injury, miRNA expression profiles of mouse thymus with or without IR were analyzed using deep sequencing technology. Potential target candidates of the identified miRNA were predicted using RNAhybrid and miRanda. Differently expressed miRNA targets functional annotation and pathways were noted using Swiss-Prot, Gene Ontology (GO), Clusters of Orthologous Groups (COG), Kyoto Encyclopedia of Genes and Genomes (KEGG) and non-redundant (NR) databases. In this study, there were 112 differently expressed miRNAs identified, including 45 known mature and 67 novel miRNAs, which meanwhile contained 77 up-regulated and 35 down-regulated miRNAs. The results of quantitative RT-polymerase chain reaction (qRT-PCR) verification were in agreement with the sequencing analysis. And the target genes of miRNA were annotated. These results revealed the differences of miRNA expression, further extended the biological knowledge and greatly facilitated future studies on the function of miRNA in IR-induced thymus injury.

A new and important relationship between miRNA‐147a and PDPK1 in radiotherapy

“…In the radiation injury model, the expression of miR‐147 and PI3K/AKT was the opposite. MiR‐147 significantly increased after radiation, but the PI3K/AKT signaling pathway was inhibited. MiR‐147 inhibits the PI3K/AKT/mTOR signaling pathway to prevented proliferation and migration of breast cancer cells, but its direct target was not elucidated .…”

“…In PDPK1 gene knockout cells or mice, AKT kinases were inactivated, indicating that PDPK1 was an important upstream kinase of AKT, and the loss of AKT activity was related to restriction of phosphorylation of itself . MiR‐147 significantly increased after radiation, but the PI3K/AKT signaling pathway was inhibited . MiR‐147 inhibits the PI3K/AKT/mTOR signaling pathway to prevented proliferation and migration of breast cancer cells, but its direct target was not elucidated …”

Activation of long-non-coding RNA NEAT1 sponging microRNA-147 inhibits radiation damage by targeting PDPK1 in troxerutin radioprotection

“…miR-147 was upregulated in the mouse thymus in response to ionizing radiation by deep sequencing analysis. 15 It was also found that up-regulation of miR-147 inhibited the expression of pro-inflammatory cytokines (such as TNF-α and IL-6), indicating that miR-147 exhibited potent anti-inflammatory properties and functions as a negative regulator of TLR/NF-κB-mediated pro-inflammatory cytokines. 32 In the radiation damage model, miR-147 and PI3K/PDPK1/AKT expression trends are exactly the opposite.…”

“… 32 In the radiation damage model, miR-147 and PI3K/PDPK1/AKT expression trends are exactly the opposite. It was observed that the level of miR-147 was significantly upregulated, 15 whereas activation of the PI3K/AKT signaling pathway was inhibited. 33 , 34 No study has analyzed miR-147 expression in response to radiation exposure.…”

“… 13 , 14 miR-147 was also upregulated in mouse thymus responses to ionizing radiation by deep sequencing analysis. 15 …”