Department of Antenatal Diagnosis, Weifang People's Hospital, Weifang, 261041, China.
Department of Gynecology, Weifang People's Hospital, Weifang, 261041, China.
Arch Biochem Biophys. 2020 May 15;684:108334. doi: 10.1016/j.abb.2020.108334. Epub 2020 Mar 12.
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调控因子参与了卵巢癌细胞的进展和化疗耐药。本研究发现,与相应对照相比,组蛋白结构域包含 2A(JMJD2A)而非 JMJD2B 或 JMJD2C 的表达在卵巢癌细胞和组织中增加。JMJD2A 的敲低可以降低 OC 细胞的增殖能力,同时增加顺铂(CDDP)的敏感性。通过筛选参与卵巢癌进展的细胞因子的表达,我们发现 JMJD2A 的敲低可以抑制卵巢癌细胞中白细胞介素-6(IL-6)和白细胞介素-8(IL-8)的表达。重组白细胞介素-6(rIL-6)和 rIL-8 可以减弱 si-JMJD2A 抑制的 OC 细胞的恶性程度。从机制上讲,JMJD2A 可以直接与 IL-6 的启动子结合,触发其转录。对于 IL-8,JMJD2A 可以增加 OC 细胞中其 mRNA 的稳定性。综上所述,我们揭示了 JMJD2A 通过上调 IL-6 和 IL-8 引发 OC 细胞的恶性程度。这表明 JMJD2A 可能是治疗卵巢癌的潜在靶点。