Overexpression of Yin Yang 1 in bone marrow-derived human multiple myeloma and its clinical significance
Overexpression of Yin Yang 1 in bone marrow-derived human multiple myeloma and its clinical significance
复制标题
DOI：
10.3892/ijo.2014.2511
复制
发表时间：
2014-09-01
影响因子：
5.2
通讯作者：
Bonavida, Benjamin
中科院分区：
文献类型：
--
作者：
Huerta-Yepez, Sara;Liu, Hong;Bonavida, Benjamin
多发性骨髓瘤（MM）患者最初对常规治疗有反应，然而，许多患者产生耐药性并复发。我们已经报道在其他肿瘤中，转录因子阴阳1（YY 1）是一种耐药因子，因此，我们假设YY 1可能在MM中过表达。与正常BM中的表达相比，在MM细胞系和22例MM患者的骨髓来源（BM）MM中观察到YY 1的表达（染色强度和细胞频率）显著升高。较高的核YY1染色与疾病进展相关。数据集中mRNA的生物信息学分析证实了上述发现，并显示与正常组织和其他造血系统疾病相比，MM中YY 1的显著过表达。YY1表达在耐药性调节中的作用在用YY1 siRNA转染的耐药性MM细胞系中举例说明，并且该耐药性MM细胞系显示对硼替佐米诱导的细胞凋亡敏感。这些发现强调了YY 1表达水平在MM患者中的潜在预后意义，并作为治疗靶点。
Multiple myeloma (MM) patients initially respond to conventional therapy, however, many develop resistance and have recurrences. We have reported in other tumors that the transcription factor Yin Yang 1 (YY1) is a resistant factor and, thus, we hypothesized that YY1 may be overexpressed in MM. Significantly, higher expression (staining intensity and cell frequency) of YY1 in MM cell lines and in bone marrow-derived (BM) MM from 22 MM patients was observed as compared to expression in normal BM. Higher nuclear YY1 staining was associated with disease progression. Bioinformatic analyses of mRNA in data sets corroborated the above findings and showed significant overexpression of YY1 in MM compared to normal tissues and other hematopoietic disorders. The role of YY1 expression in the regulation of drug resistance was exemplified in a drug-resistant MM cell line transfected with YY1 siRNA and which was shown to be sensitized to bortezomib-induced apoptosis. These findings highlight the potential prognostic significance of YY1 expression level in MM patients and as a therapeutic target.