miR-34s增强结直肠癌细胞对放射敏感性的作用研究

目的:探讨miR-34s对结直肠癌细胞放射敏感性的影响以及在电离辐射致DNA损伤中的作用。方法:利用实时荧光定量PCR(real-time quantitative fluorescence PCR,qRT-PCR)检测miR-34a/b/c-5p在结直肠癌细胞中的表达水平,以及电离辐射后miR-34a/b/c-5p表达水平变化趋势。基于克隆形成法和单击多靶模型建立细胞存活曲线,分析miR-34a/b/c-5p对结直肠癌细胞放射敏感性的影响。过表达miR-34a/b/c-5p并进行照射,利用免疫荧光法检测照射后γH2AX焦点形成情况,进而分析miR-34a/b/c-5p对电离辐射致DNA损伤的作用。结果:miR-34a/b/c-5p在HCT116细胞中的表达水平明显高于HT29细胞(P<0.05)。HCT116细胞经4 Gy照射后24 h内,miR-34a/b/c-5p表达水平呈双峰变化趋势。与miR-NC组相比,过表达miR-34a/b/c-5p可显著增加结直肠癌细胞的放射敏感性,miR-34a/b/c-5p组细胞平均致死剂量(D_(0))和准阈值剂量(D_(q))均明显降低,且辐射增敏比(SER)明显增加。过表达miR-34a/b/c-5p可显著增加电离辐射诱导的DNA双链断裂(double strand breaks,DSBs)水平,照射后1 h和8 hγH2AX焦点数明显高于miR-NC组(P<0.05)。结论:miR-34s为放射响应miRNA分子,过表达miR-34s可增加电离辐射诱导的DNA损伤水平并增强结直肠癌细胞的放射敏感性。

Delaying Vascular Aging with Chinese Medicine:Implications from An Overview of the p53 and miR-34s Family

p53 is an important target for studying vascular aging.However,as people gradually learned more about the miR-34s and the relationship between miR-34s and p53,new research idea emerged.This paper tries to elaborate the feature of p53,microRNA and miR-34s in-depth,analyze the regulatory action of miR-34s on p53,and offer some new prevention and treatment prospects about vascular aging in Chinese medicine.