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miR-145在肾细胞癌患者肿瘤细胞中低表达及其临床意义

Low expression of miR-145 in tumor cells from renal cell carcinoma patients and its clinical significance

  • 摘要:
    目的 鉴定与肾细胞癌CD40信号调控相关的micro-RNA,探讨micro-RNA对肾细胞癌CD40信号的调控作用,为未来肾细胞癌的诊治提供新的有效潜在靶点。
    方法 通过基因芯片分析肾细胞癌与癌旁对照细胞的micro-RNA表达谱差异,通过生物信息学预测可能调控CD40的micro-RNA,并通过RT-PCR验证其表达。体外转染目标micro-RNA inhibitor及mimics,研究其对CD40、CD40L表达的影响,及对肾细胞癌细胞分泌细胞因子和细胞增殖能力的影响。
    结果 miR-145在肾细胞癌中表达显著降低(P < 0.01);转染miR-145 inhibitor后,CD40在肾细胞癌细胞中表达显著增高,CD40L表达变化差异无统计学意义;转染miR-145 mimics后,CD40在肾细胞癌细胞中表达显著降低,CD40L表达变化无统计学差异。功能性高表达miR-145后,TNF-α及IFN-γ的表达显著下降,肿瘤细胞增殖减慢,功能性低表达miR-145后,TNF-α及IFN-γ的表达显著增高,肿瘤细胞增殖加快(P < 0.01)。拮抗CD40表达后,miR-145高表达,TNF-α及IFN-γ的表达量有下调趋势,但差异无统计学意义。
    结论 miR-145在肾细胞癌细胞中显著降低,并通过调控CD40的表达,进一步调控细胞因子分泌及细胞增殖,促进肿瘤的发生与发展。

     

    Abstract:
    Objective To identify the micro-RNAs related to the regulation of CD40 signaling, and explore their roles in regulating the CD40 signaling in renal cell carcinoma, which may provide new and effective potential targets for the diagnosis and treatment of renal cell carcinoma in the future.
    Methods The micro-RNA expression profiles of renal cell carcinoma and adjacent control cells were analyzed by gene chip. Bioinformatics predicted the micro-RNA that may regulate CD40, and its expression was verified by RT-PCR. Micro-RNA inhibitors and mimics were transfected in vitro to study their effects on the expression of CD40 and CD40L, and their effects on the secretion of cytokines and cell proliferation of renal cell carcinoma cells.
    Results The expression of miR-145 was significantly reduced in the renal cell carcinoma group(P < 0.01). After transfection with miR-145 inhibitor, CD40 expression was significantly increased in renal cell carcinoma cells, and there was no statistical difference in CD40L expression. After the transfection of miR-145 mimics, CD40 expression was significantly reduced in renal cell carcinoma cells, and there was no statistical difference in CD40L expression. After functionally elevating the expression of miR-145, the expression of tumor necrosis factor-α(TNF-α) and interferon-γ(IFN-γ) decreased significantly, and tumor cell proliferation slowed. After functionally decreasing the expression of miR-145, the expression of TNF-α and IFN-γ increased significantly, and tumor cell proliferation accelerated(P < 0.01). After antagonizing the expression of CD40 and elevating the expression of miR-145, TNF-α, and IFN-γ were down regulated, but there was no statistical difference.
    Conclusion miR-145 is significantly reduced in renal cell carcinoma cells, and by regulating the expression of CD40, it further regulates cytokine secretion and cell proliferation and promotes the occurrence and development of tumors.

     

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