Emerging evidence shows that histone modification and its related regulators are involved in the progression and chemoresistance of ovarian cancer (OC) cells. Our present study found that the expression of Jumonji C domain-containing 2A (JMJD2A), while not JMJD2B or JMJD2C, is increased in OC cells and tissues as compared with that in their corresponding controls. Knockdown of JMJD2A can decrease proliferation while increase cisplatin (CDDP) sensitivity of OC cells. By screening the expression of cytokines involved in the progression of ovarian cancer, we found that knockdown of JMJD2A can inhibit the expression of interleukin-6 (IL-6) and IL-8 in ovarian cancer cells. Recombinant IL-6 (rIL-6) and rIL-8 can attenuate si-JMJD2A-suppressed malignancy of OC cells. Mechanistically, JMJD2A can directly bind with the promoter of IL-6 to trigger its transcription. For IL-8, JMJD2A can increase it mRNA stability in OC cells. Collectively, we revealed that JMJD2A can trigger the malignancy of OC cells via upregulation of IL-6 and IL-8. It suggested that JMJD2A might be a potential target for OC treatment and therapy.

越来越多的证据表明，组蛋白修饰及其相关的调节剂与卵巢癌（OC）细胞的进展和化学抗性有关。我们的研究发现，OC细胞和组织中含有Jumonji C结构域的2A（JMJD2A）的表达（而不是JMJD2B或JMJD2C）与相应的对照相比有所增加。抑制JMJD2A可以减少增殖，同时增加OC细胞的顺铂（CDDP）敏感性。通过筛选参与卵巢癌进展的细胞因子的表达，我们发现敲低JMJD2A可以抑制卵巢癌细胞中白介素6（IL-6）和IL-8的表达。重组IL-6（rIL-6）和rIL-8可以减轻si-JMJD2A抑制的OC细胞恶性程度。机械上，JMJD2A可以直接与IL-6的启动子结合以触发其转录。对于IL-8，JMJD2A可以增加其在OC细胞中的mRNA稳定性。总体而言，我们揭示了JMJD2A可以通过上调IL-6和IL-8触发OC细胞的恶性肿瘤。这表明JMJD2A可能是OC治疗和治疗的潜在靶标。