Department of Gynaecology, Hainan General Hospital, Haikou, Hainan Province, China.
Department of Gynaecology, The Fourth People's Hospital of Haikou, Haikou, Hainan Province, China.
Cell Cycle. 2021 Jul;20(14):1441-1454. doi: 10.1080/15384101.2021.1941625. Epub 2021 Jul 8.
Long non-coding RNA (lncRNA) differentiation antagonizing non-protein coding RNA (DANCR) participates in the development of diverse cancers. Nevertheless, the impact of DANCR on cervical cancer (CC) remains largely unknown. This study aims to explore the effects of DANCR sponging microRNA-145-3p (miR-145-3p) on CC. Expression of KLF5, DANCR, miR-145-3p, and zinc finger E-box binding homeobox 1 (ZEB1) in CC and adjacent normal tissues was determined. Human CC cell lines were, respectively, treated with silenced DANCR or miR145-3p mimic/inhibitor. Then, the viability, migration, invasion, and apoptosis of CC cells were measured. The cell growth was observed as well. Chromatin immunoprecipitation assay was performed to analyze the binding of KLF5 and DANCR promoter. Interaction among DANCR, miR-145-3p, and ZEB1 was assessed. KLF5, DANCR, and ZEB1 were upregulated but miR-145-3p was downregulated in CC tissues. KLF5 activated DANCR expression and the high DANCR expression was related to tumor staging, infiltrating muscle depth and lymphatic metastasis of CC patients. Reduced DANCR or elevated miR-145-3p repressed malignant behaviors of CC cells. The tumor diameter and weight were also repressed by DANCR silencing or miR-145-3p elevation. The effect of DANCR knockdown on CC cells could be reversed by miR-145-3p inhibitor. MiR-145-3p was targeted by DANCR and ZEB1 was targeted by miR-145-3p. KLF5-induced overexpression of DANCR promotes CC progression via suppressing miR-145-3p to target ZEB1. This study may provide potential targets for CC treatment.
长链非编码 RNA(lncRNA)差异拮抗非蛋白编码 RNA(DANCR)参与多种癌症的发生发展。然而,DANCR 对宫颈癌(CC)的影响仍知之甚少。本研究旨在探讨 DANCR 海绵 microRNA-145-3p(miR-145-3p)对 CC 的影响。检测 CC 及相邻正常组织中 KLF5、DANCR、miR-145-3p 和锌指 E 盒结合同源框 1(ZEB1)的表达。分别用沉默 DANCR 或 miR145-3p 模拟物/抑制剂处理人 CC 细胞系。然后,测量 CC 细胞的活力、迁移、侵袭和凋亡。观察细胞生长情况。进行染色质免疫沉淀试验以分析 KLF5 和 DANCR 启动子的结合。评估 DANCR、miR-145-3p 和 ZEB1 之间的相互作用。CC 组织中 KLF5、DANCR 和 ZEB1 上调,miR-145-3p 下调。KLF5 激活 DANCR 表达,高 DANCR 表达与 CC 患者的肿瘤分期、浸润肌肉深度和淋巴转移有关。降低 DANCR 或升高 miR-145-3p 可抑制 CC 细胞的恶性行为。DANCR 沉默或 miR-145-3p 升高也抑制了 CC 细胞的肿瘤直径和重量。DANCR 敲低对 CC 细胞的影响可被 miR-145-3p 抑制剂逆转。miR-145-3p 是 DANCR 的靶点,ZEB1 是 miR-145-3p 的靶点。KLF5 诱导的 DANCR 过表达通过抑制 miR-145-3p 靶向 ZEB1 促进 CC 进展。本研究可为 CC 治疗提供潜在靶点。