Zhao Zhibin, Shen Xiaoxue, Zhang Dongli, Xiao Hongmei, Kong Hongfang, Yang Bin, Yang Li
Department of Gastroenterology, Taizhou People's Hospital, Taizhou, Jiangsu 225300, P.R. China.
Oncol Lett. 2021 Apr;21(4):300. doi: 10.3892/ol.2021.12561. Epub 2021 Feb 17.
Pancreatic cancer is one of the deadliest diseases, due to the lack of early symptoms and resistance to current therapies, including radiotherapy. However, the mechanisms of radioresistance in pancreatic cancer remain unknown. The present study explored the role of microRNA-153 (miR-153) in radioresistance of pancreatic cancer. It was observed that miR-153 was downregulated in pancreatic cancer and positively correlated with patient survival time. Using stably-infected pancreatic cancer cells that overexpressed miR-153 or miR-153 inhibitor, it was found that miR-153 overexpression sensitized pancreatic cancer cells to radiotherapy by inducing increased cell death and decreased colony formation, while cells transfected with the miR-153 inhibitor promoted radioresistance. Further investigation demonstrated that miR-153 promoted radiosensitivity by directly targeting jagged canonical Notch ligand 1 (JAG1). The addition of recombinant JAG1 protein in the cell cultures reversed the therapeutic effect of miR-153. The present study revealed a novel mechanism of radioresistance in pancreatic cancer and indicated that miR-153 may serve as a potential therapeutic target for radioresistance.
胰腺癌是最致命的疾病之一，原因在于缺乏早期症状以及对包括放疗在内的当前疗法具有抗性。然而，胰腺癌中放射抗性的机制仍不清楚。本研究探讨了微小RNA - 153（miR - 153）在胰腺癌放射抗性中的作用。据观察，miR - 153在胰腺癌中表达下调，且与患者生存时间呈正相关。使用稳定感染的过表达miR - 153或miR - 153抑制剂的胰腺癌细胞，发现miR - 153过表达通过诱导细胞死亡增加和集落形成减少使胰腺癌细胞对放疗敏感，而转染miR - 153抑制剂的细胞则促进放射抗性。进一步研究表明，miR - 153通过直接靶向锯齿状经典Notch配体1（JAG1）促进放射敏感性。在细胞培养物中添加重组JAG1蛋白可逆转miR - 153的治疗效果。本研究揭示了胰腺癌放射抗性的一种新机制，并表明miR - 153可能作为放射抗性的潜在治疗靶点。
