Yang Xiao-Dong, Xu Xiao-Hui, Zhang Shu-Yu, Wu Yong, Xing Chun-Gen, Ru Gan, Xu Hong-Tao, Cao Jian-Ping
Department of General Surgery, The Second Affiliated Hospital of Soochow University No. 1055, Suzhou 215004, China.
Department of General Surgery, The First People's Hospital of Taicang City, Taicang Affiliated Hospital of Soochow University No. 58, Taicang, Suzhou 215400, China.
Am J Cancer Res. 2015 Jan 15;5(2):545-59. eCollection 2015.
The prognosis of radioresistant colorectal cancer (CRC) is generally poor. Abnormal expression of microRNAs (miRNAs) is involved in the radiosensitivity of various tumor cells as these RNAs regulate biological signaling pathways. However, radioresistance-associated miRNAs in CRC have not yet been identified. In this study, we filtered out HCT116 and CCL-244 from seven CRC cell lines that showed the highest difference in radiosensitivity in a clonogenic assay. MiRNA sequencing identified 33 differentially expressed miRNAs (13 up-regulated and 20 down-regulated) in CCL-244 and 37 in HCT116 (20 up-regulated and 17 down-regulated) cells. MiR-100 was significantly down-regulated in CCL-244 cells after X-ray irradiation but not in HCT116 cells. Quantitative real-time PCR showed that the expression of miR-100 in CRC tissues was significantly lower than that in normal tissues. Thus, miR-100 seems to be involved in the radioresistance of CCL-244 cells. MiR-100 up-regulation sensitized CCL-244 cells to X-ray irradiation, which probably led to apoptosis and DNA double-strand breaks in these. In conclusion, to our knowledge, this is the first study to show that miR-100 may play an important role in regulating the radiosensitivity of CRC, and it may act as a new clinical target for CRC radiotherapy.
放射抗拒性结直肠癌(CRC)的预后通常较差。微小RNA(miRNA)的异常表达参与了各种肿瘤细胞的放射敏感性,因为这些RNA调节生物信号通路。然而,CRC中与放射抗拒相关的miRNA尚未被鉴定出来。在本研究中,我们在克隆形成试验中从七种CRC细胞系中筛选出了放射敏感性差异最大的HCT116和CCL-244。miRNA测序鉴定出CCL-244细胞中有33个差异表达的miRNA(13个上调和20个下调),HCT116细胞中有37个(20个上调和17个下调)。X射线照射后,miR-100在CCL-244细胞中显著下调,但在HCT116细胞中未下调。定量实时PCR显示,CRC组织中miR-100的表达明显低于正常组织。因此,miR-100似乎参与了CCL-244细胞的放射抗拒。miR-100上调使CCL-244细胞对X射线照射敏感,这可能导致这些细胞凋亡和DNA双链断裂。总之,据我们所知,这是第一项表明miR-100可能在调节CRC放射敏感性中起重要作用的研究,它可能作为CRC放疗的一个新的临床靶点。