Overexpression of let-7e enhances the radiosensitivity of colorectal cancer cells by directly targeting IGF-1R

Introduction & Aim: Abnormal expression of various microRNAs (miRNAs) has a strong association with cancer resistance to radiotherapy. The let-7 family of miRNAs as tumor suppressors, have shown to be down-regulated in different types of human malignancies including colorectal cancer (CRC). However, the biological function of let-7 members in the processes of resistance to radiation in CRC have not yet been completely elucidated. So, it seems as an attractive target for anticancer therapy. The aim of this study is to investigate the role of let-7e-5p in radiosensitivity of CRC through targeting IGF-1R as a candidate of radiation resistance. Methods: In this study, by using bioinformatics analysis it has been revealed that IGF-1R is a direct target of let-7e member. Based on this, after transfecting HCT-116 cells with let-7e-5p mimic, gene and protein expression IGF-1R was evaluated by RT-qPCR and western blot. Furthermore, in order to elucidate the effect of miRNA transfection on response to radiation, colony forming assay was followed. Finally, percentage of the sub-G1 fraction was obtained from flow cytometry to determine apoptosis. Results: Our findings showed that overexpressed let-7e by reducing the IGF-1R expression, suppressed growth and proliferation of CRC cells through induction of apoptosis, which relatively decreased survival of transfected cells from radiation (more radiosensitive) than the primary cells. Conclusion: Our data indicate that let-7e directly regulates multiple signaling pathways involve in resistance to radiation and directly represses mechanisms underlying this process which may provide a potential target for the future of cancer therapy resistance.

کلیدواژه ها:

Radioresistance ، let-7 ، IGF-1R ، Colorectal neoplasms