Su Huafang, Jin Xiance, Zhang Xuebang, Xue Shengliu, Deng Xia, Shen Lanxiao, Fang Ya, Xie Congying
Department of Medicine & Radiation Oncology, The First Affiliated Hospital of Wenzhou Medical University, No. 2 Fuxue Lane, Wenzhou, 325000, China.
Cell Biol Int. 2014 Mar;38(3):318-25. doi: 10.1002/cbin.10202. Epub 2013 Nov 18.
Radioresistance is considered as the most important reason for local tumour recurrence. This study investigates the role of miRNAs in radioresistant human esophageal cancer cells. Human miRNA microarray has been used to detect the differential expressed microRNAs between radioresistant esophageal cell line KYSE-150R and the parental cell line KYSE-150. The relative expression of some candidate miRNAs was measured by quantitative real-time PCR (qRT-PCR). Potential mRNA targets were analysed bioinformatically. Significant upregulation of 10 microRNAs and downregulation of 25 microRNAs were detected. The statistical significance of downregulation in hsa-miR-301a, hsa-miR-141 and hsa-miR-18b expression (P < 0.05) were confirmed by qRT-PCR. The correlation of the predicted microRNA target genes to apoptosis (63 genes), cell cycle (67 genes), DNA damage and repair (18 genes) were confirmed by functional annotation. The downregulation of hsa-miR-301a promoted radioresistance in KYSE-150R through the upregulation of wnt1, indicating that wnt/β-catenin signal pathway might be important in radioresistance. In conclusion, a unique set of miRNAs and their expression profiles in radiation resistance have been identified, providing a solid basis for future studies to investigate the target genes of these miRNAs and their function.
放射抗性被认为是局部肿瘤复发的最重要原因。本研究调查了微小RNA(miRNA)在放射抗性人食管癌细胞中的作用。人类miRNA微阵列已用于检测放射抗性食管癌细胞系KYSE - 150R和亲本细胞系KYSE - 150之间差异表达的微小RNA。通过定量实时PCR(qRT - PCR)测量一些候选miRNA的相对表达。通过生物信息学分析潜在的mRNA靶标。检测到10种微小RNA显著上调和25种微小RNA下调。通过qRT - PCR证实了hsa - miR - 301a、hsa - miR - 141和hsa - miR - 18b表达下调的统计学意义(P < 0.05)。通过功能注释证实了预测的微小RNA靶基因与细胞凋亡(63个基因)、细胞周期(67个基因)、DNA损伤和修复(18个基因)的相关性。hsa - miR - 301a的下调通过上调wnt1促进了KYSE - 150R中的放射抗性,表明wnt/β - 连环蛋白信号通路可能在放射抗性中起重要作用。总之,已经鉴定出一组独特的miRNA及其在辐射抗性中的表达谱,为未来研究这些miRNA的靶基因及其功能提供了坚实的基础。