MicroRNA-298 determines the radio-resistance of colorectal cancer cells by directly targeting human dual-specificity tyrosine(Y)-regulated kinase 1A

BACKGROUND Radiotherapy stands as a promising therapeutic modality for colorectal cancer(CRC);yet,the formidable challenge posed by radio-resistance significantly undermines its efficacy in achieving CRC remission.AIM To elucidate the role played by microRNA-298(miR-298)in CRC radio-resistance.METHODS To establish a radio-resistant CRC cell line,HT-29 cells underwent exposure to 5 gray ionizing radiation that was followed by a 7-d recovery period.The quantification of miR-298 levels within CRC cells was conducted through quantitative RT-PCR,and protein expression determination was realized through Western blotting.Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and proliferation by clonogenic assay.Radio-induced apoptosis was discerned through flow cytometry analysis.RESULTS We observed a marked upregulation of miR-298 in radio-resistant CRC cells.MiR-298 emerged as a key determinant of cell survival following radiation exposure,as its overexpression led to a notable reduction in radiation-induced apoptosis.Intriguingly,miR-298 expression exhibited a strong correlation with CRC cell viability.Further investigation unveiled human dual-specificity tyrosine(Y)-regulated kinase 1A(DYRK1A)as miR-298’s direct target.CONCLUSION Taken together,our findings underline the role played by miR-298 in bolstering radio-resistance in CRC cells by means of DYRK1A downregulation,thereby positioning miR-298 as a promising candidate for mitigating radioresistance in CRC.

Bimetallic nanoparticles as cascade sensitizing amplifiers for low-dose and robust cancer radio-immunotherapy

Radiotherapy(RT)is one of the most feasible and routinely used therapeutic modalities for treating malignant tumors.In particular,immune responses triggered by RT,known as radio-immunotherapy,can partially inhibit the growth of distantly spreading tumors and recurrent tumors.How-ever,the safety and efficacy of radio-immunotherapy is impeded by the radio-resistance and poor immu-nogenicity of tumor.Herein,we report oxaliplatin(IV)-iron bimetallic nanoparticles(OXA/Fe NPs)as cascade sensitizing amplifiers for low-dose and robust radio-immunotherapy.The OXA/Fe NPs exhibit tumor-specific accumulation and activation of OXA(I)and Fe^(2+)in response to the reductive and acidic microenvironment within tumor cells.The cascade reactions of the released metallic drugs can sensitize RT by inducing DNA damage,increasing ROS and O_(2) levels,and amplifying the immunogenic cell death(ICD)effect after RT to facilitate potent immune activation.As a result,OXA/Fe NPs-based low-dose RT triggered a robust immune response and inhibited the distant and metastatic tumors effectively by a strong abscopal effect.Moreover,a long-term immunological memory effect to protect mice from tumor rechal-lenging is observed.Overall,the bimetallic NPs-based cascade sensitizing amplifier system offers an effi-cient radio-immunotherapy regimen that addresses the key challenges.

Expression profiles of radio-resistant genes in colorectal cancer cells

Objective:To develop new biomarkers for radio-resistance in colorectal cancer(CRC)to improve radiotherapy efficacy at lower position and late phase of CRC patients.Methods:The human CRC cell lines were irradiated by a total dose of 40 Gy.RAN-seq screened differentially expressed genes(DEGs)related to radio-resistance.We orientated the genes which play a vital role in radioresistance by bio-informatics analysis.Ultimately,the genetic expressions were verified by qPCR.Results:3,823radio-resistance genes were found in RKO cells and 4,057 DEGs were in HCT116 cells,compared with the same type cells without radiation treatment.Data of enrichment analysis showed that DEGs obtained from two cell lines were mainly involved in cell cycle,cell division,cell skeleton,cell adhesion,DNA replication,DNA damage and DNA repair,and enrichment of glycometabolism,p53 and HIF-1 signaling pathways.The 10 candidate biomarkers were predicted according to the interaction with each other,and 5 genes(CD44,CXCL-8,ITGA5,ITGB8 and STAT1)were confirmed markedly up-regulated in two cell lines.Conclusion:Radio-resistance of CRC cells induced by X-irradiation changed the variety of genes expression,and those nodes among these genes network interaction may play core regulatory roles,which will provide new therapeutic strategies for clinical radiotherapy。