Radioresistance poses a major challenge in the treatment of advanced rectal cancer. Therefore, understanding the detailed mechanisms of radioresistance may improve patient response to irradiation and the survival rate. To identify the novel targets that modulate the radiosensitivity of rectal cancer, we performed small RNA sequencing with human rectal cancer cell lines. Through bioinformatics analysis, we selected microRNA-310a (miR-130a) as a promising candidate to elucidate radioresistance. miR-130a was dramatically upregulated in radiosensitive rectal cancer cells and overexpression of miR-130a promotes rectal cancer cell radiosensitivity. Mechanically, miR-130a reversed the epithelial-mesenchymal transition phenotype of rectal cancer cells following inhibition of cell invasion upon irradiation. Moreover, miR-130a also inhibited the repair of irradiation-induced DNA damage followed by cell death. We identified that SOX4 was a direct target of miR-130a. Overexpression of SOX4 reversed the promotion activity of miR-130a on radiosensitivity. Together, our findings suggest that miR-130a functions as a radiosensitizer in rectal cancer and reveals a potential therapeutic target and preoperative prognostic marker for radiotherapy.

放射抗性对晚期直肠癌的治疗提出了重大挑战。因此，了解放射抗性的详细机制可以改善患者对放射的反应和存活率。为了确定调节直肠癌放射敏感性的新靶标，我们对人直肠癌细胞系进行了小分子RNA测序。通过生物信息学分析，我们选择了microRNA-310a（miR-130a）作为阐明抗辐射性的有前途的候选人。miR-130a在放射敏感性直肠癌细胞中显着上调，miR-130a的过表达促进直肠癌细胞放射敏感性。在机械上，miR-130a在抑制放射线对细胞侵袭后，逆转了直肠癌细胞的上皮-间质转化表型。而且，miR-130a还抑制了辐射诱导的DNA损伤随后细胞死亡的修复。我们确定SOX4是miR-130a的直接靶标。SOX4的过表达逆转了miR-130a对放射敏感性的促进活性。在一起，我们的发现表明，miR-130a在直肠癌中起放射增敏剂的作用，并揭示了放射治疗的潜在治疗靶点和术前预后标志物。