Department of Gynecology and Obstetrics, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, Fujian 362000, P.R. China.
Department of Gynecology and Obstetrics, Jinjiang Traditional Chinese Medicine Hospital, Jinjiang, Fujian 362200, P.R. China.
Oncol Rep. 2020 Oct;44(4):1343-1354. doi: 10.3892/or.2020.7691. Epub 2020 Jul 15.
Increasing research has demonstrated that lncRNAs participate in the development of multiple cancer types. However, the role of TTN‑AS1 in endometrial cancer (EC) remains unknown. The present study aimed to explore the function of titin‑antisense RNA1 (TTN‑AS1) in EC progression and the underlying mechanisms. qRT‑PCR was performed to assess the TTN‑AS1 expression patterns in EC tissues and cell lines. Loss of function experiments were carried out to estimate the effects of TTN‑AS1 on EC cell proliferation, migration and invasion. To reveal the underlying mechanisms, informatics tools were used to predict the targets. Rescue experiments were performed to investigate the TTN‑AS1‑regulated miR‑376a‑3p/pumilio homolog 2 (PUM2) axis involved. The results of the present study revealed that TTN‑AS1 was highly expressed in both EC tissues and cell lines, and TTN‑AS1 knockdown inhibited EC cell proliferation, migration and invasion. With respect to the mechanisms, miR‑376a‑3p was revealed to be targeted by TTN‑AS1, and reversed the effects on EC development induced by TTN‑AS1. In addition, PUM2 was positively regulated by TTN‑AS1, and miR‑376a‑3p mediated the regulation between them. Furtherly, in vivo experiments confirmed the results. Collectively, TTN‑AS1 enhanced EC cell proliferation and metastasis by targeting the miR‑376a‑3p/PUM2 axis, which may shed light on EC diagnosis and treatment.
越来越多的研究表明,lncRNAs 参与多种癌症类型的发展。然而,TTN-AS1 在子宫内膜癌(EC)中的作用尚不清楚。本研究旨在探讨肌联蛋白反义 RNA1(TTN-AS1)在 EC 进展中的作用及其潜在机制。qRT-PCR 用于评估 EC 组织和细胞系中 TTN-AS1 的表达模式。进行功能丧失实验以评估 TTN-AS1 对 EC 细胞增殖、迁移和侵袭的影响。为了揭示潜在的机制,使用信息学工具预测了靶标。进行了挽救实验以研究 TTN-AS1 调节的 miR-376a-3p/ pumilio 同源物 2(PUM2)轴。本研究的结果表明,TTN-AS1 在 EC 组织和细胞系中均高度表达,并且 TTN-AS1 敲低抑制了 EC 细胞的增殖、迁移和侵袭。就机制而言,发现 miR-376a-3p 是 TTN-AS1 的靶标,并逆转了 TTN-AS1 对 EC 发育的影响。此外,PUM2 被 TTN-AS1 正向调控,并且 miR-376a-3p 介导了它们之间的调节。进一步,体内实验证实了这些结果。总之,TTN-AS1 通过靶向 miR-376a-3p/PUM2 轴增强 EC 细胞的增殖和转移,这可能为 EC 的诊断和治疗提供新的思路。