Department of Gynecology, Hengshui People's Hospital, Hengshui, Hebei 053000, P.R. China.
Department of Gynecology, Hebei University of Chinese Medicine, Shijiazhuang, Hebei 050000, P.R. China.
Oncol Rep. 2021 May;45(5). doi: 10.3892/or.2021.8013. Epub 2021 Mar 24.
Long non‑coding RNA forkhead box D3 antisense RNA 1 (FOXD3‑AS1) functions as an oncogenic regulator in several types of cancer, including breast cancer, glioma and cervical cancer. However, the effects and mechanisms underlying FOXD3‑AS1 in cervical cancer (CC) are not completely understood. The present study aimed to investigate the biological functions and potential molecular mechanisms underlying FOXD3‑AS1 in CC progression. Reverse transcription‑quantitative PCR was performed to detect FOXD3‑AS1, microRNA (miR)‑128‑3p and LIM domain kinase 1 (LIMK1) expression levels in CC tissues and cells. Immunohistochemical staining and western blotting were conducted to assess LIMK1 protein expression levels in CC tissues and cells, respectively. Cell Counting Kit‑8 and BrdU assays were used to determine the role of FOXD3‑AS1 in regulating cell proliferation. CC cell migration and invasion were assessed by performing Transwell assays. Dual‑luciferase reporter assays were conducted to verify the binding between miR‑128‑3p and FOXD3‑AS1. FOXD3‑AS1 expression was significantly increased in CC tissues and cell lines compared with adjacent healthy tissues and normal cervical epithelial cells, respectively. High FOXD3‑AS1 expression was significantly associated with poor differentiation of tumor tissues, increased tumor size and positive lymph node metastasis. FOXD3‑AS1 overexpression significantly increased CC cell proliferation, migration and invasion compared with the negative control (NC) group, whereas FOXD3‑AS1 knockdown resulted in the opposite effects compared with the small interfering RNA‑NC group. Moreover, the results demonstrated that FOXD3‑AS1 targeted and negatively regulated miR‑128‑3p, which indirectly upregulated LIMK1 expression. Therefore, the present study demonstrated that FOXD3‑AS1 upregulated LIMK1 expression via competitively sponging miR‑128‑3p in CC cells, promoting CC progression.
长链非编码 RNA 叉头框 D3 反义 RNA 1(FOXD3-AS1)在多种类型的癌症中发挥致癌调节因子的作用,包括乳腺癌、神经胶质瘤和宫颈癌。然而,FOXD3-AS1 在宫颈癌(CC)中的作用和机制尚不完全清楚。本研究旨在探讨 FOXD3-AS1 在 CC 进展中的生物学功能和潜在分子机制。采用逆转录-定量 PCR 检测 CC 组织和细胞中 FOXD3-AS1、微小 RNA(miR)-128-3p 和 LIM 结构域激酶 1(LIMK1)的表达水平。免疫组织化学染色和蛋白质印迹法分别检测 CC 组织和细胞中 LIMK1 蛋白的表达水平。细胞计数试剂盒-8 和 BrdU 检测用于确定 FOXD3-AS1 调节细胞增殖的作用。通过 Transwell 检测评估 CC 细胞迁移和侵袭。双荧光素酶报告基因检测验证 miR-128-3p 与 FOXD3-AS1 之间的结合。与相邻健康组织和正常宫颈上皮细胞相比,CC 组织和细胞系中 FOXD3-AS1 的表达显著增加。FOXD3-AS1 高表达与肿瘤组织分化不良、肿瘤体积增大和阳性淋巴结转移显著相关。与阴性对照(NC)组相比,FOXD3-AS1 过表达显著增加了 CC 细胞的增殖、迁移和侵袭,而与小干扰 RNA-NC 组相比,FOXD3-AS1 敲低则产生相反的效果。此外,研究结果表明,FOXD3-AS1 通过竞争性结合 miR-128-3p 靶向并负调控 miR-128-3p,间接上调 LIMK1 表达。因此,本研究表明,FOXD3-AS1 通过在 CC 细胞中竞争性地吸附 miR-128-3p 而上调 LIMK1 表达,从而促进 CC 进展。