The role of microRNAs in response to ionizing radiation in cancer cells

MicroRNAs (miRNA) are a class of conserved RNAs (with a length of ۱۹-۲۳ nucleotides) that are non-coding and act as post-transcriptional regulators of gene expression. miRNAs play an important role in the pathophysiology of diseases such as cancer by regulating cell proliferation, metabolism, cell cycle, metastasis, and DNA damage response (۱, ۲). Many studies have identified miRNA as a potential biomarker for diagnosis, prognosis, or therapeutic tool for cancer.Ionizing radiation (IR) is one of the methods of cancer treatment using ionizing radiation, which is used in the treatment of more than ۵۰% of cancers. Cellular response to IR damages activates many signalling pathways (such as PI۳K/AKT and MAPK) mediating reacting to the damage and activating DNA damage responses (DDR) by activity homologous recombination (HR) and non-homologous end-joining (NHEJ) to restore the double-strand breaks (DSBs).Recent studies have shown that miRNAs play a role in the signalling pathway related to radiation response and may lead to apoptosis, autophagy, DNA damage response, repair, etc (۳). There is increasing interest for researchers to investigate the correlation between changes in some miRNA profiles and IR exposure. In this presentation, we will briefly overview the examples of different microRNAs and their role in response to radiation in some cancers.The PI۳K/Akt pathway is activated in response to IR exposure and causes radioresistance. miRNA-۲۱ caused radioresistance by reducing the activity of PTEN (tumour suppressor), thus increasing AKT activation (۴). Also, miRNA-۲۰۵ was shown to regulate radiosensitivity by modulation of PTEN in gastric cancer. We also highlighted that some miRNAs can impact DNA damage repair and radioresistance of cancer cells. Many studies investigated the roles of miRNAs in two main mechanisms for DSB lesions for IR which include HR and NHEJ pathways. For example, miR-۸۷۵ can induce radiosensitivity by regulating checkpoint kinase ۱ (CHK۱) expression directly to inhibit the HR pathway in prostate cancer cells (۵). However, overexpression of miR-۱۸۲ enhances radiosensitivity by inhibiting HR through reducing BRCA۱ expression (۶). Upregulation of miR-۲۰۵ in PC-۳ cell lines reduced the NHEJ pathway efficiency and caused radiosensitivity by targeting DNA-PKC(۷).In summary, we highlighted the role of miRNAs in the radioresistance of cancers and discussed their effects on the main signalling pathways in response to ionizing radiation exposure.

کلیدواژه ها:

Micro RNA ، radiation resistance ، biomarkers ، Radiotherapy ، Signalling pathway