JMJD2A facilitates growth and inhibits apoptosis of cervical cancer cells by downregulating tumor suppressor miR-491-5p

Abstract

Cervical cancer remains the second most common malignancy for women worldwide. Jumonji domain containing 2A (JMJD2A), a member of the JmjC domain-containing family of JMJD2 proteins, is capable of regulating cancer-associated genes, including genes involved in the cell cycle, proliferation, apoptosis, invasion and metastasis. However, its role in human cervical cancer has yet to be elucidated. microRNA (miR)-491-5p, a mature form of miR-491, has been shown to function as a tumor suppressor gene in vitro by inducing apoptosis and inhibiting proliferation and invasion in various types of cancer. However, the underlying mechanism remains to be elucidated. In the present study it was observed that JMJD2A expression was significantly upregulated in human cervical cancer cell lines and cervical epithelial carcinoma tissues. A high JMJD2A level predicted poor overall and disease-free survival rate and may serve as an independent prognostic factor for adverse outcome. JMJD2A increased cervical cancer cell and colony numbers in vitro, increased the tumor weight in a mouse xenograft model, and decreased the apoptotic rate by downregulating the pro-apoptotic proteins Bax, p21 and active caspase-3, and upregulating the anti-apoptotic protein Bcl-2. Transfection experiments indicated that the role of JMJD2A in cervical cancer was mediated, at least in part, by the repression of miR-491-5p. In summary, JMJD2A was identified as an oncogenic protein in human cervical cancer that significantly affected cell and colony numbers, tumor weight and apoptosis via the downregulation of miR-491-5p, which acts as a tumor suppressor in cervical cancer. Therefore, JMJD2A may serve as a prognostic factor and potential target for intervention in cervical cancer.