Department of Gynecology and Obstetrics, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, P.R. China.
Department of Gynecology and Obstetrics, Banan People's Hospital of Chongqing, Chongqing 401320, P.R. China.
Mol Med Rep. 2019 Apr;19(4):2489-2496. doi: 10.3892/mmr.2019.9916. Epub 2019 Jan 31.
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.
宫颈癌仍然是全球女性第二大常见恶性肿瘤。组蛋白去甲基化酶 JMJD2 家族成员 2A（JMJD2A）能够调节癌症相关基因，包括参与细胞周期、增殖、凋亡、侵袭和转移的基因。然而，其在人宫颈癌中的作用尚未阐明。miR-491-5p 是 miR-491 的成熟形式，已被证明在体外通过诱导细胞凋亡和抑制多种类型癌症的增殖和侵袭来发挥肿瘤抑制基因的作用。然而，其潜在机制仍有待阐明。在本研究中，观察到 JMJD2A 在人宫颈癌细胞系和宫颈上皮样癌细胞组织中的表达明显上调。高 JMJD2A 水平预示着总生存率和无病生存率较差，可能是不良预后的独立预后因素。JMJD2A 在体外增加宫颈癌细胞和集落数量，在小鼠异种移植模型中增加肿瘤重量，并通过下调促凋亡蛋白 Bax、p21 和活性 caspase-3 以及上调抗凋亡蛋白 Bcl-2 来降低细胞凋亡率。转染实验表明，JMJD2A 在宫颈癌中的作用至少部分是通过抑制 miR-491-5p 介导的。综上所述，JMJD2A 被鉴定为人类宫颈癌中的致癌蛋白，通过下调 miR-491-5p 显著影响细胞和集落数量、肿瘤重量和凋亡，miR-491-5p 在宫颈癌中作为肿瘤抑制因子发挥作用。因此，JMJD2A 可能作为宫颈癌的预后因素和潜在的干预靶点。
