Shi Yanping, Jia Li, Wen Hongli
Department of Gynaecology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, People's Republic of China.
Department of Gynaecology, Chongqing Traditional Chinese Medicine Hospital, Chongqing 400021, People's Republic of China.
Cancer Manag Res. 2020 Nov 2;12:10993-11003. doi: 10.2147/CMAR.S274856. eCollection 2020.
Endometrial cancer (EC) is one of the most common gynecological malignancies. Circular RNAs (circRNAs) play crucial roles in the occurrence and development of tumors. This research aimed to explore the function and potential mechanism of human serum albumin (hsa)_circ_0109046 in EC.
The abundance of circ_0109046, microRNA-136 (miR-136) and high-mobility group AT-hook 2 (HMGA2) was detected by quantitative real-time polymerase chain reaction or Western blot. Cell counting kit-8 (CCK-8) and colony formation assays were employed to assess cell proliferation. Transwell assay was used to measure cell migration and invasion. The levels of E-cadherin, Vimentin and N-cadherin were examined by Western blot. The binding association among circ_0109046, miR-136 and HMGA2 was verified by dual-luciferase reporter assay, RNA pull-down assay and RNA immunoprecipitation assay. Xenograft assay was performed to test tumor growth in vivo.
Circ_0109046 and HMGA2 were up-regulated, and miR-136 was down-regulated in EC tissues and cells. Knockdown of circ_0109046 impeded the proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) of EC cells. Moreover, miR-136 knockdown reversed the suppression of circ_0109046 silencing on EC development. HMGA2 overexpression abolished the inhibition of miR-136 on EC progression. Besides, depletion of circ_0109046 inhibited EC growth in vivo.
Circ_0109046 accelerated EC progression via modulating miR-136/HMGA2 axis, indicating that circ_0109046 might be a promising therapeutic target for EC.
子宫内膜癌（EC）是最常见的妇科恶性肿瘤之一。环状RNA（circRNAs）在肿瘤的发生发展中起关键作用。本研究旨在探讨人血清白蛋白（hsa）_circ_0109046在子宫内膜癌中的功能及潜在机制。
通过定量实时聚合酶链反应或蛋白质免疫印迹法检测circ_0109046、微小RNA-136（miR-136）和高迁移率族AT钩蛋白2（HMGA2）的丰度。采用细胞计数试剂盒-8（CCK-8）和集落形成试验评估细胞增殖。Transwell试验用于检测细胞迁移和侵袭能力。通过蛋白质免疫印迹法检测E-钙黏蛋白、波形蛋白和N-钙黏蛋白的水平。通过双荧光素酶报告基因试验、RNA下拉试验和RNA免疫沉淀试验验证circ_0109046、miR-136和HMGA2之间的结合关系。进行异种移植试验以检测体内肿瘤生长情况。
在子宫内膜癌组织和细胞中，circ_0109046和HMGA2表达上调，miR-136表达下调。敲低circ_0109046可抑制子宫内膜癌细胞的增殖、迁移、侵袭及上皮-间质转化（EMT）。此外，敲低miR-136可逆转circ_0109046沉默对子宫内膜癌发展的抑制作用。HMGA2过表达可消除miR-136对子宫内膜癌进展的抑制作用。此外，circ_0109046缺失可抑制体内子宫内膜癌的生长。
Circ_0109046通过调节miR-136/HMGA2轴促进子宫内膜癌进展，表明circ_0109046可能是子宫内膜癌一个有前景的治疗靶点。
