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长链非编码 RNA 通过作为 microRNA-744 的竞争性内源性 RNA 发挥作用,从而增加 Bcl-2 表达,促进宫颈癌的发生。

Long noncoding RNA promotes tumorigenesis in cervical cancer by acting as a competing endogenous RNA of microRNA-744 and consequently increasing Bcl-2 expression.

机构信息

Department of Gynaecology and Obstetrics, Gaomi People's Hospital, Gaomi, Shandong, P.R. China.

Department of Neurosurgery, Gaomi People's Hospital, Gaomi, Shandong, P.R. China.

出版信息

Cell Cycle. 2020 May;19(10):1222-1235. doi: 10.1080/15384101.2020.1749468. Epub 2020 Apr 8.

Abstract

The expression of a long noncoding RNA termed is dysregulated in breast cancer and laryngeal squamous cell carcinoma, and this dysregulation affects various tumor-associated biological processes. To our knowledge, the expression status and detailed roles of in cervical cancer as well as its regulatory mechanisms of action remain unknown. Therefore, the objectives of this study were to measure expression in cervical cancer, investigate the effects of on cervical cancer cells, and identify the mechanism underlying these effects. Herein, was found to be highly expressed in cervical cancer tissues and cell lines. High expression significantly correlated with the International Federation of Gynecology and Obstetrics (FIGO) stage, lymph node metastasis, and shorter overall survival among the patients with cervical cancer. Functional assays revealed that interference with expression suppressed cervical cancer cell proliferation, migration, and invasion in vitro; induced apoptosis in vitro; and impeded tumor growth in vivo. In addition, was demonstrated to act as a competing endogenous RNA of microRNA-744 (miR-744) and consequently increase B-cell lymphoma 2 (Bcl-2 or BCL2) expression levels in cervical cancer cells. Furthermore, either inhibition of miR-744 or restoration of Bcl-2 expression neutralized the effects of the silencing on the malignant characteristics of cervical cancer cells. Thus, promotes the aggressiveness of cervical cancer in vitro and in vivo by upregulating miR-744-Bcl-2 axis output. The -miR-744-Bcl-2 pathway may be involved in cervical cancer pathogenesis and could serve as a novel target for anticancer therapies.

摘要

长链非编码 RNA 的表达在乳腺癌和喉鳞状细胞癌中失调,这种失调会影响各种与肿瘤相关的生物学过程。据我们所知,在宫颈癌中, 的表达状态和详细作用及其作用机制尚不清楚。因此,本研究的目的是测量 在宫颈癌中的表达,研究 对宫颈癌细胞的影响,并确定这些影响的作用机制。在此,我们发现 在宫颈癌组织和细胞系中高度表达。高 表达与国际妇产科联盟(FIGO)分期、淋巴结转移以及宫颈癌患者的总生存时间显著相关。功能分析表明,干扰 表达可抑制宫颈癌细胞在体外的增殖、迁移和侵袭;诱导体外细胞凋亡;并阻碍体内肿瘤生长。此外, 被证明是 microRNA-744(miR-744)的竞争性内源性 RNA,从而增加宫颈癌细胞中 B 细胞淋巴瘤 2(Bcl-2 或 BCL2)的表达水平。此外,miR-744 的抑制或 Bcl-2 表达的恢复可中和 沉默对宫颈癌细胞恶性特征的影响。因此, 通过上调 miR-744-Bcl-2 轴的输出,促进宫颈癌在体外和体内的侵袭性。-miR-744-Bcl-2 通路可能参与宫颈癌的发病机制,并可作为抗癌治疗的新靶点。

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