YY1 is a novel potential therapeutic target for the treatment of HPV infection-induced cervical cancer by arsenic trioxide.
YY1 is a novel potential therapeutic target for the treatment of HPV infection-induced cervical cancer by arsenic trioxide.
复制标题
DOI：
10.1097/igc.0b013e31821d2525
复制
发表时间：
2011-08
期刊：
影响因子：
--
通讯作者：
Yu L
中科院分区：
文献类型：
--
作者：
He G;Wang Q;Zhou Y;Wu X;Wang L;Duru N;Kong X;Zhang P;Wan B;Sui L;Guo Q;Li JJ;Yu L
YY1是一种锌指转录因子，参与细胞生长、发育和分化的调控。虽然YY 1可以调节人乳头瘤病毒型（HPV）病毒癌基因E6和E7，但YY 1是否在HPV感染细胞的癌进展中起关键作用仍不清楚。在此，我们试图确定YY 1是否在宫颈癌组织中上调，以及YY 1抑制是否有助于宫颈癌细胞的凋亡，这至少部分依赖于p53。因此，YY 1可能成为三氧化二砷（As2O3）治疗宫颈癌的潜在靶点。采用Western blot方法检测并分析经病理证实的原发性宫颈癌组织、癌旁正常组织及正常宫颈组织中YY1的表达水平。通过Western blot分析p53水平、细胞生长曲线、集落形成试验和细胞凋亡来检测特异性siRNA对HeLa细胞中YY 1的抑制作用。Western blot和细胞周期分析检测YY 1对As2O3诱导的p53活化和凋亡的作用。在这里，我们报告说，YY1的表达水平显着升高，在原发性癌组织。在HPV阳性的HeLa细胞中，siRNA介导的YY1抑制诱导细胞凋亡并增加p53的表达。用已知的抗宫颈癌药物As2O3处理HeLa细胞，可降低Hela细胞中YY1的蛋白和mRNA水平。YY1基因敲除显著增强As2O3诱导的细胞凋亡。这些结果表明，YY1在宫颈癌中表达上调，并且YY1在HPV阳性宫颈癌的进展中起关键作用。此外，YY1抑制诱导HPV感染的HeLa细胞中的p53活化和凋亡。因此，YY 1是As2O3靶点，可作为抗宫颈癌治疗的潜在药物增敏剂。
YY1 is a zinc-finger transcription factor involved in regulation of cell growth, development, and differentiation. Although YY1 can regulate human papillomavirus type (HPV) viral oncogene E6 and E7, it remains unknown if YY1 plays a key role in carcinoma progression of HPV infected cells. Here we sought to determine whether YY1 is up-regulated in the cervical cancer tissues and YY1 inhibition contributes to apoptosis of cervical cancer cells which is at least partly p53 dependent. Therefore, YY1 can be a potential therapeutic target for cervical cancer treatment by arsenic trioxide (As2O3). YY1 expression level was examined and analyzed by Western blot in pathologically confirmed primary cervical cancer samples, the adjacent normal samples as well as normal cervix samples. The effects of YY1 inhibition by specific siRNA in HeLa cells were determined by Western blot analysis of p53 level, cell growth curve, colony formation assay, and apoptosis. The contribution of YY1 to As2O3-induced p53 activation and apoptosis were also examined by Western blot and cell cycle analysis. Here we report that the YY1 expression level is significantly elevated in the primary cancer tissues. In HPV-positive HeLa cells, siRNA-mediated YY1 inhibition induced apoptosis and increased the expression of p53. Treatment of HeLa cells with As2O3, a known anti-cervical cancer agent, reduced both protein and mRNA levels of YY1 in Hela cells. YY1 knockdown significantly further enhanced As2O3-induced apoptosis. These results demonstrated that YY1 expression is up-regulated in cervical carcinomas and YY1 plays a critical role in the progression of HPV-positive cervical cancer. In addition, YY1 inhibition induces p53 activation and apoptosis in HPV-infected HeLa cells. Thus, YY1 is an As2O3 target and could serve as a potential drug sensitizer for anti-cervical cancer therapy.