AIB1影响卵巢癌预后及增强卵巢癌对顺铂抵抗的研究

Associated of AIB1 with Poor Prognosis and Enhances Cisplatin Resistance in Ovarian Cancer

据报道,乳腺癌扩增因子(AIB1)能促进乳腺癌的发生发展和转移。然而,AIB1和卵巢癌的发生发展关系尚不清楚。本研究提取了TCGA数据库中卵巢癌患者癌组织的mRNA表达数据,利用在线软件Kaplan-Meier plotter分别分析了aib1基因表达与卵巢癌患者以及经过顺铂治疗过的患者的总生存期(OS)、进展后生存期(PPS)和无进展生存期(PFS)之间的相关性。结果表明,无论在总的卵巢癌患者群体中还是在顺铂治疗后的群体中,aib1基因高表达患者的OS、PPS以及PFS都显著降低。在人卵巢癌细胞系(SKVO3)中,通过转染AIB1过表达质粒和小干扰RNA(siRNA),分别上调和下调AIB1表达来检测SKVO3对顺铂的敏感性。结果表明,上调AIB1表达抑制了SKVO3细胞对顺铂的敏感性,而下调AIB1表达促进了SKVO3细胞对顺铂的敏感性。进一步研究发现,AIB1高表达上调了卵巢癌细胞中B淋巴细胞瘤-2(BCL2)、B细胞淋巴瘤/白血病x基因长片段(BCL2L1)的表达,而干扰AIB1表达下调了细胞中BCL2、BCL2L1的表达。通过提取TCGA数据库中的卵巢癌患者癌组织mRNA表达数据,利用在线软件GEPIA分析了aib1基因mRNA表达与bcl2、bcl2l1基因mRNA表达的相关性。结果发现,aib1基因表达与bcl2、bcl2l1基因表达呈显著正相关。其结果进一步表明,AIB1可能调节BCL2和BCL2L1的表达。总之,AIB1能作为判断卵巢癌预后的标志物以及卵巢癌治疗的潜在分子靶点,并且抑制AIB1能够增强顺铂对卵巢癌的治疗效果。本研究为卵巢癌对顺铂抵抗的机制提供了新的见解,对克服卵巢癌化疗抵抗具有一定的价值。

Amplified in breast cancer 1(AIB1)can promote the tumorigenesis,development and metastasis in breast cancer.However,the association between AIB1 expression and the tumorigenesis and development of ovarian cancer is still not clear.In this study,we extracted the mRNA expression data of ovarian cancer tissues from TCGA database,and analyzed the correlation between aib1 expression and overall survival(OS),post progression survival(PPS)and progression free survival(PFS)in ovarian cancer patients by using online software Kaplan-Meier plotter.Results showed that OS,PPS and PFS were significantly reduced in patients with aib1 high expression in both all patient population and the DDP-treated population.In SKVO3 cell line transfected with AIB1 over expression plasmid and siRNA was found to up-regulate and down-regulate AIB1 expression respectively,and then the sensitivity of cells to DDP(cis-dichlorodiammine platinum,DDP)was detected.Results showed that up-regulation of AIB1 inhibited the sensitivity of SKVO3 cells to DPP,whereas down-regulation of AIB1 promoted the sensitivity of SKVO3 cells to DPP.Further study showed that the high expression of AIB1 up-regulated the expression of anti-apoptotic proteins B-cell lymphoma-2(BCL2)and B-cell lymphoma/leukemia x long form(BCL2L1)in SKVO3 cells,while the depletion of AIB1 down-regulated the expression of BCL2 and BCL2L1 in ovarian cancer cells.The mRNA expression data of cancer tissues from ovarian cancer patients was extracted from the TCGA database,and the association between aib1 mRNA levels and the mRNA expression of bcl2 and bcl2l1 was analyzed by online software GEPIA.We found that aib1 expression was positively correlated with bcl2 and bcl2l1 expression.These results further suggested that AIB1 might regulate the expression of BCL2 and BCL2L1.Altogether,our results showed that AIB1 could be used as a potential marker for the prognosis of ovarian cancer and a potential molecular target for the treatment of ovarian cancer.Moreover,this study also found that inhibition of AIB1 can enhance the therapeutic effect of DDP in ovarian cancer.This study provided new insights for the pathogenesis of ovarian cancer resistance to DDP,and has certain value for overcoming ovarian cancer chemotherapy resistance.