Cancerous inhibitor of protein phosphatase 2A is overexpressed in cervical cancer and upregulated by human papillomavirus 16 E7 oncoprotein

Abstract

Objectives Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a recently identified oncoprotein stabilizing c-Myc and promoting cell proliferation and transformation. Here we investigated the role of CIP2A in cervical cancer in vivo and in vitro. Methods CIP2A expression was assessed in normal cervical, cervical intraepithelial neoplasia (CIN) I to III and cervical cancer tissues by immunohistochemistry and RT-PCR. Cell growth was explored by cell proliferation assay, colony formation assay and anchorage-independent growth in soft agar after inhibition of CIP2A by siRNA in HeLa, SiHa and Caski cells. Crosstalk of CIP2A and HPV16 E7 was investigated by immunohistochemistry in cervical cancer tissues and by real-time PCR and western blot analysis after HPV16 E7 inhibition by siRNA in SiHa cells. Results CIP2A was transcribed in 73.3% of cervical cancer tissues (n = 15) but not in normal cervical tissues (n = 8). CIP2A protein was detected in 52.8% of cervical cancer (n = 72) and 12.5% of CIN III tissues (n = 24) but not in normal (n = 15), CIN I (n = 21) or CIN II samples (n = 25). CIP2A protein level was positively associated with HPV16 E7 level in cervical cancer tissues. CIP2A expression was markedly reduced after E7 depletion. Moreover, CIP2A depletion reduced c-Myc protein level and impaired proliferation and growth of cervical cancer cells. Conclusions CIP2A is overexpressed in cervical cancer and promotes the malignant growth of cervical cancer cells. Its expression is upregulated by HPV16 E7. Therefore, CIP2A plays an important role in carcinogenisis of cervical cancer and shows promise for the diagnosis and treatment of cervical cancer.