Screening Biomarker MicroRNAs For Predicting The Response Of Rectal Cancer To Chemoradiotherapy Based On Regulatory Network

Objective: Radiotherapy or chemoradiotherapy has become a basic procedure for treatment of patients with rectal cancer(RC).However,patients' responses to treatment are different and personalized.MicroRNAs(miRNAs)play important roles in the radiosensitivity of RC and thus become promising biomarkers for predicting the radiosensitivity of RC.This study aimed to identify the biomarker miRNAs associated with the chemoradiotherapy efficacy of RC and promote the fundamental study of RC in terms of chemoradiotherapy.Methods: MiRNAs associated with RC radiosensitivity were mined and collected via PubMed.Differentially expressed miRNAs were retrieved from the miRNA expression dataset.Predictive miRNAs were identified after the filtration of the bioinformatics model.Systematic and integrative bioinformatics analysis were performed to confirm the predicted biomarker miRNAs associated with the chemoradiotherapy of RC.Results: A total of 30 publicly reported miRNAs associated with radiosensitivity of RC were collected.Forty-six miRNAs were found to be differentially expressed between samples of responders and non-responders to radiotherapy from the selected datasets(Student's t test,p-value < 0.05 and |fold-change| > 2).Using the bioinformatics model,miR-198,miR-765,miR-671-5p,miR-630,miR-371-5p,miR-575,miR-202,miR-483-5p and miR-513a-5p were identified as potential biomarkers for the radiosensitivity of RC.Literature validation and functional enrichment analysis were performed for confirming the reliability of the predicted biomarkers.Seven of the candidates were then experimentally verified by Q-PCR in the radiosensitive and insensitive colorectal cancer cell lines.Western blot analyses revealed that upon transfection of the miRNA mimics in the radiosensitive cell line,the unique target genes of miR-198 and miR-765 were altered significantly.Conclusions: miR-198,miR-765,miR-630,miR-371-5p,miR-575,miR-202 and miR-513a-5p could be used to predict the chemoradiotherapy response of RC.