| dc.description.abstract | Radiotherapy is a common type of cancer treatment used for treating head and neck cancer (HNSCC), and rectal cancer (RC). Unfortunately, the local recurrence or metastasis leads to treatment failure. Today, there are no effective methods for evaluating the risk of cancer recurrence. MicroRNAs (miRNA) are involved in post-transcriptional gene regulation. In addition, miRNAs are packed into extracellular vesicles and released into the body fluids that have played a role in cell communication. Hence, the miRNA expression in the body fluids is considered a potential target of liquid biopsy. To date, no research has suggested that the miRNA expression in the blood could regulate cancer radiosensitivity or play the role of message transport. Therefore, we have discovered miRNA as a blood biomarker by investigating the miRNA expression level in the plasma samples. Also, the candidate miRNA expression in plasma could be considered an important indicator for promoting radioresistant.
In this research, the high-throughput method was used to select the 22 miRNAs as the candidates for radiation response. Nine miRNAs’ expressions showed a significant change after radiotherapy. Furthermore, the expression level of three miRNAs and the four miRNA ratios significantly changes in the poor responsive group. The public data also showed the expression of miR-519d-3p in the tissue of HNSCC is associated with a 5-year survival period. Finally, two prediction models were established for predicting the response of radiotherapy after six months of treatment by multiple logistic regression.
DNA breaks are the majorly caused by radiotherapy. This occurrence induces cell apoptosis and cell-cycle arrest by the DNA damage response. In chapter three, the activities of three miRNAs, including miR-342-5p, miR-148a-3p, and miR-323a-3p, involved in the radioresistance or regulation of the genes by DNA damage response remain unclear. We delved into the radiation effect of miR-148a-3p in HNSCC. The result showed that the expression level of miR-148a-3p was significantly decreased by radiation in the HNSCC cell line. Moreover, overexpression of the miR-148a-3p increased the radiation effect by the tests of cell viability, migration, and colony formation ability. Furthermore, immunofluorescence staining showed that miR-148a-3p also increased the DNA damage level further causing genome instability. MiR-148a-3p may regulate integrin alpha 5 (ITGA5), Rho-associated, coiled-coil-containing protein kinase 1 (ROCK1), 14-3-3, and increase the effect of radiation. Interestingly, miR-148a-3p are released into the conditioned media (CM). Radiation suppresses the release of miR-148a-3p in CM and further induces the cell viability and migration ability of non-radiated bystander cells. Moreover, a high expression level of miR-148a-3p in CM inhibits these effects.
Taken together, the in vivo study shows that miR-148a-3p may not only play an important role in the radiation effect but may change the signaling of miR-148a-3p in tumor microenvironments. | en_US |