Abstract
BackgroundRadiotherapy (RT) is considered an important therapeutic strategy in the fight against colorectal cancer (CRC). However, the existence of some radioresistance factors becomes the main challenge for the RT. Recently, non-coding RNAs (ncRNAs) have shown an important role in modulating cancer cell responses to ionizing radiation (IR). It is therefore of great significance to elucidate the exact mechanisms of ncRNAs in IR-mediated responses to CRC.MethodsMicroarrays were used to identify specific miRNAs that may be altered in response to IR. Bioinformatics, luciferase reporter analyses were used to explore the targets of miR-6778-5p. CircRNA CBL.11 was identified to bind with miR-6778-5p by bioinformatic analysis, AGO2 immunoprecipitation and biotinylated RNA pull-down assay. Functional experiments, including CCK-8 assay, cell colony formation assay and EdU incorporation were conducted to investigate the biological roles of miR-6778-5p and circular RNA CBL.11.ResultsMiR-6778-5p was suppressed in CRC cells after irradiation. Results of functional experiments indicated that miR-6778-5p promoted the proliferation of CRC cells. Luciferase reporter analyses showed that YWHAE was a target of miR-6778-5p, which mediated the function of miR-6778-5p in the proliferation of CRC cells via the p53 pathway. Furthermore, we have noticed that after carbon ion irradiation, circRNA CBL.11 was increased in CRC cells and could function as a competing endogenous RNA (ceRNA) to regulate YWHAE expression by sponging miR-6778-5p, resulting in regulation the proliferation of CRC cells.ConclusionCircRNA CBL.11 may play an important role in improving the efficacy of carbon ion RT against CRC.
Highlights
Radiotherapy (RT) is considered an important therapeutic strategy in the fight against colorectal cancer (CRC)
MiR-6778-5p decreased after carbon ion irradiation To identify specific miRNAs that may be altered after carbon ion irradiation, we examined the miRNA expression profiles of HCT116 cells before/after different doses of carbon ion irradiation (Additional file 5 and Additional file 6)
Because miR-6778-5p was down-regulated after different doses of radiation treatment, we further validated the data in three different colon cancer cell lines (HCT116, HT29 and SW620)
Summary
Radiotherapy (RT) is considered an important therapeutic strategy in the fight against colorectal cancer (CRC). Non-coding RNAs (ncRNAs) have shown an important role in modulating cancer cell responses to ionizing radiation (IR). As mentioned in the literatures, Li et al BMC Cancer (2019) 19:826 their biogenesis processes and potential mechanisms for regulating tumor progression in RT, especially using high-LET radiation, remain largely unknown. Several miRNAs have shown a role in directly regulating the expression of genes associated with radiosensitivity [10]. Some miRNAs whose expression profiles could be altered upon irradiation are involved in the mechanism of ionizing radiation (IR) response [13]. It is clear that the causal effects of miRNAs on tumor radiosensitivity and their action mechanisms in ncRNA regulatory networks are still in their infancy
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