SOX9, a potential tumor suppressor in cervical cancer, transactivates p21(WAF1/CIP1) and suppresses cervical tumor growth

Sex-determining region Y-box 9 protein (SOX9) is a transcription factor that may act as both oncogene and tumor suppressor depending on tumor origin. Here we found that SOX9 expression was progressively decreased in cervical carcinoma in situ and especially in invasive cervical carcinoma, compared with normal cervix tissue. The effects of SOX9 on the proliferation, viability, and tumor formation of cervical carcinoma cells were assessed through the silencing and overexpression of SOX9. Overexpression of SOX9 in cervical carcinoma cells (SiHa and C33A) inhibited cell growth in vitro and tumor formation in vivo. In agreement, the silencing of SOX9 in HeLa cells promoted cell growth in culture and tumor formation in mice. Overexpression of SOX9 transactivated p21(WAF1/CIP1) via a specific promoter region, thus blocking G1/S transition. The quantitative chromatin immunoprecipitation analysis revealed physical interaction between SOX9 and the specific region of the p21(WAF1/CIP1) promoter. We suggest that SOX9 is a potential therapeutic target in cervical carcinoma, that specifically transactivates p21(WAF1/CIP1).