Department of Thoracic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, P. R. China.
Cell Cycle. 2023 Mar;22(5):596-609. doi: 10.1080/15384101.2022.2138416. Epub 2022 Nov 22.
This study is designed to explore the role of long non-coding RNAs (lncRNAs) NCK1-AS1 in proliferative and invasive activities of esophageal squamous cell carcinoma (ESCC) cells by binding to microRNA-133b (miR-133b) to regulate ENPEP. Differentially expressed lncRNAs, miRs, genes and their targeting relationships were screened on ESCC-related gene expression datasets GSE17351 and GSE6188. The targeting relationships among NCK1-AS1, miR-133b, and ENPEP were verified using functional assays. Loss- and gain- of function assays were carried out to examine the roles of NCK1-AS1, miR-133b, and ENPEP in ESCC cell proliferative, invasive, migrative and apoptotic abilities as well as tumorigenesis . Elevated NCK1-AS1 and ENPEP but reduced miR-133b expression were found in ESCC. NCK1-AS1 knockdown or miR-133b overexpression inhibited the malignant properties of ESCC cells as well as tumorigenesis . NCK1-AS1 regulated the ENPEP expression by competitively binding to miR-133b. ENPEP overexpression reversed inhibition of NCK1-AS1 knockdown on the function of ESCC cells. This study provides evidence that silencing NCK1-AS1 inhibits expression of ENPEP by sponging miR-133b, thereby suppressing ESCC.
本研究旨在通过与 microRNA-133b（miR-133b）结合来调节 ENPEP，探讨长链非编码 RNA（lncRNA）NCK1-AS1 在食管鳞状细胞癌（ESCC）细胞增殖和侵袭活性中的作用。在 ESCC 相关基因表达数据集 GSE17351 和 GSE6188 上筛选差异表达的 lncRNA、miR、基因及其靶向关系。通过功能测定验证 NCK1-AS1、miR-133b 和 ENPEP 之间的靶向关系。进行失活和获得功能测定，以研究 NCK1-AS1、miR-133b 和 ENPEP 在 ESCC 细胞增殖、侵袭、迁移和凋亡能力以及肿瘤发生中的作用。在 ESCC 中发现 NCK1-AS1 和 ENPEP 升高，miR-133b 降低。NCK1-AS1 敲低或 miR-133b 过表达抑制 ESCC 细胞的恶性特性和肿瘤发生。NCK1-AS1 通过竞争性结合 miR-133b 调节 ENPEP 的表达。ENPEP 过表达逆转了 NCK1-AS1 敲低对 ESCC 细胞功能的抑制作用。本研究提供的证据表明，沉默 NCK1-AS1 通过海绵 miR-133b 抑制 ENPEP 的表达，从而抑制 ESCC。
