Department of Science and Education, Zigong Fourth People's Hospital, Zigong, Sichuan 643000, P.R. China.
Department of Reproductive Medicine, Zigong Maternity and Child Healthcare Hospital, Zigong, Sichuan 643000, P.R. China.
Mol Med Rep. 2020 Dec;22(6):5209-5218. doi: 10.3892/mmr.2020.11623. Epub 2020 Oct 21.
Telomeric repeat binding factor 1 (TERF1) has been identified as a tumor suppressor gene in numerous types of human cancer. However, the expression of TERF1 and its mechanism in prostate cancer (PCa) remains unclear. The present study aimed to explore the expression and functions of TERF1 in PCa. The UALCAN database was used to analyze the differential expression of TERF1 between normal prostate tissue and primary PCa tissue. Cell apoptosis was analyzed by Annexin V/propidium iodide staining, and wound healing and Transwell assays were used to detect the cell migration and invasion abilities, respectively. The cell viability was analyzed using an MTT assay. Reverse transcription‑quantitative PCR and western blotting were used to analyze the mRNA and protein expression levels, respectively, of epithelial‑mesenchymal transition (EMT) markers following TERF1 knockdown in the PC3 cell line. A dual luciferase reporter assay was used to verify the association between TERF1 and microRNA (miR)‑155 predicted by bioinformatics analysis. Rescue experiments were performed to determine the role of the miR‑155/TERF1 axis in regulating the cellular behaviors of PCa. The results demonstrated that the expression levels of TERF1 in the primary prostate tumors were significantly downregulated compared with in prostate normal tissue. TERF1 silencing was discovered to significantly promote cell viability, migration and invasion, while suppressing cell apoptosis. The impact of TERF1 on PC3 cells was suggested to occur through the EMT pathway. TERF1 was confirmed to be the direct target of miR‑155. The overexpression of miR‑155 promoted the viability, migration and invasion, while suppressing the apoptosis of the PC3 cell line, while the knockdown of miR‑155 in PC3 cells achieved the opposite trends. In addition, TERF1 overexpression reversed the promotive effects of upregulated miR‑155 expression levels on the migration and apoptosis of PC3 cells. On the contrary, the knockdown of TERF1 reversed the migration and apoptosis abilities of the downregulated miR‑155 expression levels on the cellular behaviors of PC3 cells. In conclusion, TERF1, as a direct target of miR‑155, was discovered to be significantly downregulated in PCa, which was suggested to promote the migration and invasion of PCa via the EMT pathway.
端粒重复结合因子 1（TERF1）已被鉴定为多种人类癌症中的肿瘤抑制基因。然而，TERF1 在前列腺癌（PCa）中的表达及其机制尚不清楚。本研究旨在探讨 TERF1 在 PCa 中的表达和功能。使用 UALCAN 数据库分析正常前列腺组织和原发性 PCa 组织中 TERF1 的差异表达。通过 Annexin V/碘化丙啶染色分析细胞凋亡，通过划痕愈合和 Transwell 测定分别检测细胞迁移和侵袭能力。使用 MTT 测定分析细胞活力。使用逆转录-定量 PCR 和 Western blot 分别分析 PC3 细胞系中 TERF1 敲低后上皮-间充质转化（EMT）标志物的 mRNA 和蛋白表达水平。使用双荧光素酶报告基因测定验证生物信息学分析预测的 TERF1 与 microRNA（miR）-155 之间的关联。进行挽救实验以确定 miR-155/TERF1 轴在调节 PCa 细胞行为中的作用。结果表明，与前列腺正常组织相比，原发性前列腺肿瘤中 TERF1 的表达水平明显下调。发现 TERF1 沉默可显著促进细胞活力、迁移和侵袭，同时抑制细胞凋亡。TERF1 对 PC3 细胞的影响似乎是通过 EMT 途径发生的。TERF1 被确认为 miR-155 的直接靶标。miR-155 的过表达促进了 PC3 细胞系的活力、迁移和侵袭，同时抑制了细胞凋亡，而在 PC3 细胞中敲低 miR-155 则呈现相反的趋势。此外，TERF1 过表达逆转了上调 miR-155 表达水平对 PC3 细胞迁移和凋亡的促进作用。相反，下调 miR-155 表达水平对 PC3 细胞的迁移和凋亡能力的降低，TERF1 的敲低则逆转了这一趋势。综上所述，作为 miR-155 的直接靶标，TERF1 在 PCa 中显著下调，通过 EMT 途径促进 PCa 的迁移和侵袭。
