Elucidating regulatory mechanisms downstream
DNA damage repair includes base excision repair, single-strand break repair and double-strand break repair [ 17–18 ].Tumor cells utilize two major pathways to repair double-strand breaks (DSBs), including the non-homologous end-joining (NHEJ) repair pathway, a fast but error-prone process in the G phase [ 19–21 ].Notably, one mi RNA can regulate the expression of many genes, and one gene can also be regulated by multiple mi RNAs.
Mi RNA binds to the 3′-untranslated regions (3′-UTR) of target genes in a complete or in an incomplete complementary manner through its ‘seed sequence’ in the 5′-region and controls expression of target genes at the post-transcriptional level.
In this review, we primarily illustrate the detailed regulatory mechanisms of mi RNA in tumor radiosensitivity from diverse aspects, including the modulation of DNA damage repair, cell cycle checkpoint, apoptosis, radio-related signal transduction pathways and TME.
We also highlight the clinical perspectives of mi RNA in the future diagnosis and treatment of tumors and further present the significance of exploring new mechanisms and discovering novel targets to improve the therapeutic effects of radiotherapy.
It interferes with four radio-related pathways in ionizing radiation, including the PI3-K/Akt, NF-κB, MAPK and TGFβ signaling pathways.
Moreover, the regulatory effect of mi RNA in radiosensitivity can be enhanced when interacting with various key molecules, including H2AX, BRCA1, ATM, DNA-PK, RAD51, Chk1, Cdc25A, p53, PLK1, HIF-1 and VEGF, which are involved in these processes.