YY1 is a novel potential therapeutic target for the treatment of HPV infection YInduced cervical cancer by arsenic trioxide

Abstract

Objective: YY1 is a zinc finger transcription factor involved in the regulation of cell growth, development, and differentiation. Although YY1 can regulate human papillomavirusYtype (HPV) viral oncogenes 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 upregulated in the cervical cancer tissues and YY1 inhibition contributes to apoptosis of cervical cancer cells, which is at least partly p 53 dependent. Therefore, YY1 can be a potential therapeutic target for cervical cancer treatment by arsenic trioxide (As 2O 3). Materials and Methods: The expression level of YY1 was examined and analyzed by Western blot in pathologically confirmed primary cervical cancer samples, in the adjacent normal samples, as well as in normal cervix samples. The effects of YY1 inhibition by specific small interfering RNA in HeLa cells were determined by Western blot analysis of p 53 level, cell growth curve, colony formation assay, and apoptosis. The contribution of YY1 to As 2O 3-induced p 53 activation and apoptosis was also examined by Western blot and cell cycle analysis. Results: Here we report that the expression level of YY1 is significantly elevated in the primary cancer tissues. In HPV-positive HeLa cells, small interfering RNAYmediated YY1 inhibition induced apoptosis and increased the expression of p 53. Treatment of HeLa cells with As 2O 3, a known antiYcervical cancer agent, reduced both protein and mRNA levels of YY1 in HeLa cells. YY1 knockdown significantly further enhanced As 2O 3- induced apoptosis. Conclusions: These results demonstrated that the expression of YY1 is upregulated in cervical carcinomas and that YY1 plays a critical role in the progression of HPV-positive cervical cancer. In addition, YY1 inhibition induces p 53 activation and apoptosis in HPVinfected HeLa cells. Thus, YY1 is an As 2O 3 target and could serve as a potential drug sensitizer for antiYcervical cancer therapy. Copyright © 2011 by IGCS and ESGO.