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长链非编码 RNA 通过表观遗传沉默 激活宫颈癌细胞中的 Wnt/β-连环蛋白信号通路。

Long Noncoding RNA Activates Wnt/β-Catenin Signaling Pathway in Cervical Cancer Cells by Epigenetically Silencing .

机构信息

Department of Obstetrics and Gynecology, the First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.

出版信息

Cancer Biother Radiopharm. 2020 Jun;35(5):329-337. doi: 10.1089/cbr.2019.3004. Epub 2020 Apr 9.

DOI:10.1089/cbr.2019.3004
PMID:32275170
Abstract

Cervical cancer (CC) ranks fourth in cancers that resulted in death among women, accumulating the attention of researchers. It has been ascertained that long noncoding RNAs (lncRNAs) are crucial players in the pathological processes of a host of cancers. And, has been reported to enhance the occurrence of various cancers; however, its function in CC sustains obscure. This study explored the function of in CC and further investigates the specific molecular mechanism of in regulating CC. The levels of in CC cells were reflected by quantitative real-time polymerase chain reaction. The functions of on CC tumorigenesis were explored by colony formation, CCK-8 (Cell Counting Kit-8), EdU (ethynyl deoxyuridine), and Western blot assays. The influences of depletion on the binding of to promoter and occupancy in promoter were studied by chromatin immunoprecipitation assay. was conspicuously higher expressed in CC cells. Knockdown of was detected to ameliorate the malignant behaviors of CC cells. Importantly, the contribution of to CC development was relied on activated Wnt pathway through DDK1-mediated manner. Furthermore, it was confirmed that silencing weakened the binding of to promoter as well as the occupancy of in promoter. epigenetically silences to exacerbate the malignancy of CC via Wnt/β-catenin signaling pathway.

摘要

宫颈癌(CC)在导致女性死亡的癌症中排名第四,引起了研究人员的关注。已经确定长非编码 RNA(lncRNA)是许多癌症病理过程中的关键参与者。并且,已经报道其增强了各种癌症的发生;然而,其在 CC 中的功能仍然不清楚。本研究探讨了在 CC 中 的功能,并进一步研究了 在调节 CC 中具体的分子机制。通过实时定量聚合酶链反应反映 CC 细胞中 的水平。通过集落形成、CCK-8(细胞计数试剂盒-8)、EdU(乙炔脱氧尿苷)和 Western blot 分析来探索 对 CC 发生的影响。 在 CC 细胞中表达水平显著升高。研究发现, 耗竭可改善 CC 细胞的恶性行为。重要的是, 对 CC 发展的贡献是通过 DDK1 介导的方式依赖于激活的 Wnt 途径。此外,还证实 沉默减弱了 与 启动子的结合以及 与 启动子的结合。 通过 Wnt/β-catenin 信号通路, 表观遗传沉默 以加剧 CC 的恶性程度。

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