Gong Pijun, Hu Chunyan, Zhou Xi, Wang Renxiao, Duan Zhao
Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
Department of Gynecology, Northwest Women and Children's Hospital, Xi'an, Shaanxi 710061, P.R. China.
Exp Ther Med. 2017 Dec;14(6):5452-5458. doi: 10.3892/etm.2017.5229. Epub 2017 Sep 29.
Human wings apart-like (hWAPL) is reported to have an association with cervical cancer. In the present study, the role of hWAPL in cervical cancer stem cells (CCSCs) was evaluated. Cervical tumorspheres were generated from cervical cancer tissues cultured in stem cell medium, and the expression of hWAPL by the tumorspheres was detected using immunohistochemistry. hWAPL expression levels in the tumorspheres were then upregulated using hWAPL adenoviral vectors or downregulated via the TAT-mediated knockdown of hWAPL and the effects on the tumorspheres were evaluated using colony formation, cell invasion and western blotting assays. The results demonstrated that the expression of hWAPL and human papillomavirus (HPV) was associated with the pluripotency of CCSCs, with hWAPL expression decreasing following the differentiation of cervical tumorspheres. Knockdown of hWAPL expression decreased HPV E6 expression and inhibited tumor invasion and colony formation. TAT-mediated knockdown of hWAPL with short interfering RNA significantly reduced tumor growth in nude mice. These results suggest that hWAPL is a marker of CCSC proliferation and is potentially a therapeutic target for cervical carcinoma through the downregulation of HPV E6.
据报道，人翼状分离蛋白（hWAPL）与宫颈癌有关。在本研究中，评估了hWAPL在宫颈癌干细胞（CCSCs）中的作用。从在干细胞培养基中培养的宫颈癌组织中生成宫颈肿瘤球，并使用免疫组织化学检测肿瘤球中hWAPL的表达。然后使用hWAPL腺病毒载体上调肿瘤球中hWAPL的表达水平，或通过TAT介导的hWAPL敲低来下调其表达水平，并使用集落形成、细胞侵袭和蛋白质印迹分析评估对肿瘤球的影响。结果表明，hWAPL和人乳头瘤病毒（HPV）的表达与CCSCs的多能性相关，随着宫颈肿瘤球的分化，hWAPL表达降低。hWAPL表达的敲低降低了HPV E6的表达，并抑制了肿瘤侵袭和集落形成。TAT介导的短发夹RNA敲低hWAPL显著降低了裸鼠体内的肿瘤生长。这些结果表明，hWAPL是CCSC增殖的标志物，并且通过下调HPV E6可能成为宫颈癌的治疗靶点。
