Applications of microRNAs in radiotherapy for head and neck cancer I

Radiotherapy is the major treatment modality for approximately 50% cancer patients including head and neck cancer patients, but in some case, the radioresistant causes tumor recurrence. The studies have reported the genomic instability, several signaling pathways and radiation-induced bystander effects (RIBE) are associated with the mechanism of radiosensitivity. However, our knowledge of radioresistance or radiosensitivity at molecular levels is still limited. MicroRNAs (miRNAs) profiles are more effective in cancer classification than mRNA profiles, indicating miRNAs would be better and novel biomarkers than canonical mRNAs in body fluid. Moreover, miRNAs act as oncomirs or as tumor suppressors applied in therapeutic targets. We have reported that two miRNA classifiers to predict the prognosis of radiotherapy from plasma (Li et al., 2018). Although 11 candidate miRNAs are associated with radiation responses or prognosis, how these candidate miRNAs are involved in the microenvironment or RIBEs, of which is a largely unknown area. We studied the radiation effects of miR-148a-3p, one of the candidate miRNAs, first and demonstrated that miR-148a-3p expression can increase radiosensitivity in irradiated and non-irradiated bystander cancer cells to reduce survival, migration and genomic stability. In this project, we will focus on not only dissecting how candidate miRNAs regulate the radiation responses signaling pathway network, but also investigating how their functions involve in RIBEs. In addition, we will verify the prognosis radiation biomarker by larger size of patient samples to predict the efficiency of radiotherapy. The ultimate goal of this proposal is to decipher the molecular network of candidate miRNAs in radiation responses; and hopefully, the knowledge we gain from this study can potentially be extended in the discovery of new prognosis or therapy targets for head and neck cancer to improve their survival.