Department of Thoracic Surgery, Affiliated Tumor Hospital of Xinjiang Medical University, Suzhou Street 789, Ürümqi, 830011, China.
Clin Transl Oncol. 2022 Oct;24(10):1954-1963. doi: 10.1007/s12094-022-02850-7. Epub 2022 Jul 1.
A growing number of evidences has revealed that long non-coding RNAs (lncRNAs) have vital effect in the pathogenesis of esophageal squamous cell carcinoma (ESCC). In our work, we found that lncRNA FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1) was significantly increased in clinical ESCC samples and cell lines.
The biological effect of FOXD2-AS1 on EC109 and KYSE150 cells showed that the low expression of FOXD2-AS1 inhibited the proliferation through CCK8 and colony formation assays, invasion by transwell chamber test, migration abilities by wound healing assay, and enhance apoptosis rates by flow cytometry assay.
Through bioinformatics analysis and luciferase reporter assays, microRNA (miR)-204-3p was proved to be a target of FOXD2-AS1. We further confirmed that FOXD2-AS1 was the upstream inhibitor of miR-204-3p and the down-regulation of miR-204-3p reversed the repressive effects of low expression of FOXD2-AS1 on ESCC progression. In addition, inhibition of FOXD2-AS1 effectively suppressed the tumor growth.
In general, our results suggested that FOXD2-AS1 may be of vital therapeutic importance for the treatment of ESCC patients.
越来越多的证据表明,长链非编码 RNA(lncRNA)在食管鳞状细胞癌(ESCC)的发病机制中具有重要作用。在我们的工作中,我们发现 lncRNA FOXD2 相邻反义链 RNA 1(FOXD2-AS1)在临床 ESCC 样本和细胞系中显著增加。
FOXD2-AS1 对 EC109 和 KYSE150 细胞的生物学效应表明,低表达 FOXD2-AS1 通过 CCK8 和集落形成实验抑制增殖,通过 Transwell 室试验抑制侵袭,通过划痕愈合试验抑制迁移能力,并通过流式细胞术检测提高凋亡率。
通过生物信息学分析和荧光素酶报告基因实验,证明 microRNA(miR)-204-3p 是 FOXD2-AS1 的靶标。我们进一步证实,FOXD2-AS1 是 miR-204-3p 的上游抑制剂,下调 miR-204-3p 逆转了低表达 FOXD2-AS1 对 ESCC 进展的抑制作用。此外,抑制 FOXD2-AS1 有效抑制了肿瘤生长。
总之,我们的结果表明,FOXD2-AS1 可能对 ESCC 患者的治疗具有重要的治疗意义。