Gai Muhuizi, Bo Qifang, Qi Lixia
Department of Gynaecology and Obstetrics, Dongying People's Hospital, No.317, East City South 1st Road, Dongying, Shandong, 257091, China.
Department of Gynaecology and Obstetrics, Dongying People's Hospital, No.317, East City South 1st Road, Dongying, Shandong, 257091, China.
Biochem Biophys Res Commun. 2016 Jan 22;469(4):1000-5. doi: 10.1016/j.bbrc.2015.12.069. Epub 2015 Dec 20.
Ovarian cancer contributes to the majority of ovarian cancer, while the molecular mechanisms remain elusive. Recently, some DEAD box protein 1 has been reported play a tumor suppressor role in ovarian cancer progression. However, the functions of DEAD box protein (DDX) members in ovarian cancer development remain largely unknown. In current study, we retrieved GEO databases and surprisingly found that DDX10 is significantly down-regulated in ovarian cancer tissues compared with normal ovary. These findings suggest that DDX10 might also play a suppressive role in ovarian cancer. We then validated the down-regulated expression pattern of DDX10 in fresh ovarian cancer tissues. Furthermore, both loss- and gain-functions assays reveal that the down-regulated DDX10 could promote ovarian cancer proliferation in vitro and the xenograft subcutaneous tumor formation assays confirmed these findings in vivo. In addition, we found that DDX10 is epigenetic silenced by miR-155-5p in ovarian cancer. Moreover, we further preliminary illustrated that down-regulated DDX10 promotes ovarian cancer cell proliferation through Akt/NF-κB pathway. Taken together, in current study, we found a novel tumor suppressor, DDX10, is epigenetic silenced by miR-155-5p in ovarian cancer, and the down-regulated expression pattern of DDX10 promotes ovarian cancer proliferation through Akt/NF-κB pathway. Our findings shed the light that DDX families might be a novel for ovarian cancer treatment.
卵巢癌在大多数卵巢癌中起作用，但其分子机制仍不清楚。最近，有报道称一些DEAD盒蛋白1在卵巢癌进展中起肿瘤抑制作用。然而，DEAD盒蛋白（DDX）成员在卵巢癌发生发展中的功能仍 largely未知。在本研究中，我们检索了GEO数据库，令人惊讶地发现与正常卵巢相比，DDX10在卵巢癌组织中显著下调。这些发现表明DDX10在卵巢癌中可能也起抑制作用。然后我们在新鲜卵巢癌组织中验证了DDX10的下调表达模式。此外，功能缺失和功能获得实验均表明，下调的DDX10可在体外促进卵巢癌增殖，异种移植皮下肿瘤形成实验在体内证实了这些发现。此外，我们发现DDX10在卵巢癌中被miR-155-5p表观遗传沉默。而且，我们进一步初步阐明下调的DDX10通过Akt/NF-κB途径促进卵巢癌细胞增殖。综上所述，在本研究中，我们发现了一种新的肿瘤抑制因子DDX10，其在卵巢癌中被miR-155-5p表观遗传沉默，并且DDX10的下调表达模式通过Akt/NF-κB途径促进卵巢癌增殖。我们的发现揭示了DDX家族可能是卵巢癌治疗的新靶点。
