Modulation Of Non-Coding RNA On The Sensitivity Of Colon Cancer Cells To Heavy Ion Radiation

Radiotherapy(RT)is a kind of cancer therapy using ionizing radiation,generally as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator.Currently,approximately 50%-70% of cancer patients require RT during their treatment.As one of the three major treatments for cancer treatment(surgery,radiotherapy,chemotherapy),because of the wide range of RT,the treatment process is relatively simple,and its curative effect is reliable,and the method is reliable.It can be used alone or in combination with surgery and chemotherapy.Therefore,the role and status of RT in cancer treatment has become increasingly prominent.Colorectal cancer(CRC)is one of the most common digestive system tumors in the world,with high malignancy and poor prognosis.According to the 2018 National Cancer Report,colorectal cancer ranks third(female)and fourth(male)in the incidence of malignant tumors in China;the fourth(female)and fifth(male)mortality rates.As an important means of clinical treatment of colorectal cancer,RT has obvious advantages in controlling tumor growth and reducing tumor volume.Similar to the RT process of most tumors,the RT of colorectal cancer also faces problems such as radiation damage to normal tissues and radiation resistance of tumor cells during RT.The high LET(Linear Eenergy Transfer)heavy ion beam has its unique Bragg Peak dose distribution compared to conventional RT rays.This physical property and high relative biological effects(RBE)make heavy ions a distinct advantage in tumor RT.Of course,there are many factors affecting radiotherapy.In addition to the types of radiation,it depends on the radiosensitivity of tumor cells.The intrinsic or acquired radiation resistance of some tumor cells greatly reduces the killing effect of radiation on them,thus limiting the application of RT.The radiosensitivity of tumor cells is affected by many factors,such as the pathological grade of the tumor,the cell cycle in which the tumor cells are located,and the oxygen content of the tumor cells.Therefore,it is important to study the response mechanism of tumor cells to radiation and the molecular mechanism of radiation resistance to improve the efficacy of radiotherapy.Recently,non-coding RNAs(ncRNAs)have shown an important role in modulating cancer cell responses to ionizing radiation(IR).However,the mechanisms of ncRNAs in IR-mediated responses for CRC remain to be investigated.In the present study,we investigated microRNA(miRNA)expression profiles in human CRC cell line HCT116 using microarrays and found that miR-6778-5p was down-regulated in response to carbon ion irradiation.Results of functional experiments,including colony formation assay,CCK-8 assay and EdU incorporation assay,demonstrated that miR-6778-5p promoted the proliferation of CRC cells.Luciferase reporter analyses showed that YWHAE was the direct target of miR-6778-5p and mediated the function of miR-6778-5p in proliferation regulation through the p53 pathway.Furthermore,we found that circRNA CBL.11 was up-regulated in CRC cells after carbon ion irradiation.Via AGO2 immunoprecipitation and RNA pull-down assay,circRNA CBL.11 was observed to directly bind to miR-6778-5p.Silencing circRNA CBL.11 in HCT116 cells could down-regulate YWHAE,resulting in promotion of cell proliferation.In addition,miR-6778-5p inhibitor could reverse the proliferation regulation of circRNA CBL.11 silencing.In conclusions,the current study demonstrated that,IR-induced increase of circRNA CBL.11 suppresses the proliferation of CRC cells via the miR-6778-5p/YWHAE axis,which might be a potential target for improving the efficacy of carbon ion RT against CRC.