基于PTEN/PI3K/Akt通路探讨血浆miRNA-125b调控多发性骨髓瘤增殖与转移的分子机制研究

我们前期发现阿司匹林（ASA）通过PI3K/Akt诱导多发性骨髓瘤（MM）细胞凋亡。新近证实miR-125b在骨髓瘤高表达，生物信息学预测PTEN为miR-125b调控PI3K/Akt信号通路的关键靶基因。提示miR-125b通过PTEN/PI3K/Akt通路参与MM生物学功能。本课题研究：1.qRT-PCR检测miRNA-125b在MM患者血浆的表达，观察其与MM分型、分期、疗效和预后的关系。2.下调miRNA-125b的表达，检测转染肿瘤细胞的增殖、迁移和转移能力。3.明确miR-125b对靶基因PTEN表达的影响及参与PI3K/Akt和MAPK等通路调控的机制，观察ASA对MM中miR-125b表达的影响。4.最终体内裸鼠成瘤实验论证miRNA-125b抑制物的抗癌作用。阐明miR-125b在MM的调控作用，为血浆miR-125b作为MM预后标志物和个体化诊疗提供新的实用靶点。

Our previous study found that aspirin can induce cell apoptosis of multiple myeloma(MM) through the PI3K/Akt pathway.Recent studies have confirmed that miR-125b is significantly overexpressed in myeloma.Bioinformatics predicts the 3’-UTR of PTEN mRNA contains the base site of miR-125b. Therefore,we speculate that miR-125b can inhibit PTEN gene, and then activate PI3K/Akt signaling pathway by which involved in the biological function of myeloma.We continue to study as follows: 1. Real-time quantitative PCR is used to detect the expression of miRNA-125b in the plasma of patients with myeloma,then investigate the effect of miR-125b down-regulation on the proliferation, migration and metastasis abilities of MM cells. 2. To verify PTEN as the target gene of miR-125b and detect the effect of miR-125b up-regulation/down-regulation on the activation of PI3K/Akt signaling pathway. 3.To investigate the effect of aspirin on the expression of miR-125b in MM cell lines.4. nude mouse models is used to analyze the anti-cancer effect of miRN-125b inhibitor, which provide ideas and drug targets for the new molecular markers of MM, and offer new clues for the invasion and metastasis mechanism of MM.