Department of Urology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Department of Andriatry, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Biomed Res Int. 2020 Aug 20;2020:1878431. doi: 10.1155/2020/1878431. eCollection 2020.
Circular RNA DDX17 (circDDX17) has been demonstrated as a tumor suppressor in colorectal cancer. However, mechanisms underlying circDDX17 effects in cases of prostate cancer (PCa) are not well understood. Thus, herein, we determined measures of circDDX17 expression by use of the TCGA database. Expression of circDDX17 in prostate cancer-afflicted tissue samples was determined by qRT-PCR. Functionally, circDDX17 induced remarkable inhibition of cell colonizing ability, invasion, and epithelial-mesenchymal transition (EMT) progression in vitro. Mechanistically, dual-luciferase reporter assays, RNA immunoprecipitation, and RNA pull-down experiments helped verify interactions between circDDX17 and miR-346. Low expression of circDDX17 occurred in TCGA PCa samples. Furthermore, circDDX17 expression was downregulated significantly in PCa. These results suggested that circDDX17 suppressed PC cell mobility, proliferation, and invasion. Mechanistic experiments indicated that circDDX17 might serve as a ceRNA of miR-346 to relieve repressive effects of miR-346 upon phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP). LHPP expression itself was downregulated in TCGA PCa samples. Overall, our findings indicated that the circDDX17/miR-346/LHPP pathway inhibited the progression of prostate cancer and that circDDX17 may be a new potential therapeutic or diagnostic target for treating and diagnosing prostate cancer. As our study also demonstrated for the first time that LHPP might act as an anticancer gene in prostate cancer, the findings could have wide-ranging implications for the treatment of this affliction.
环状 RNA DDX17(circDDX17)已被证明在结直肠癌中是一种肿瘤抑制因子。然而,circDDX17 对前列腺癌(PCa)的影响机制尚不清楚。因此,本研究通过 TCGA 数据库来确定 circDDX17 的表达水平。通过 qRT-PCR 检测前列腺癌组织样本中 circDDX17 的表达。功能上,circDDX17 在体外显著抑制细胞定植能力、侵袭和上皮间质转化(EMT)进展。机制上,双荧光素酶报告基因检测、RNA 免疫沉淀和 RNA 下拉实验验证了 circDDX17 与 miR-346 之间的相互作用。TCGA PCa 样本中 circDDX17 的表达水平较低。此外,circDDX17 在 PCa 中表达显著下调。这些结果表明 circDDX17 抑制了 PC 细胞的迁移、增殖和侵袭。机制实验表明,circDDX17 可能作为 miR-346 的 ceRNA,减轻 miR-346 对磷酸丝氨酸磷酸组氨酸无机焦磷酸磷酸酶(LHPP)的抑制作用。TCGA PCa 样本中 LHPP 的表达本身也下调了。总之,我们的研究结果表明,circDDX17/miR-346/LHPP 通路抑制了前列腺癌的进展,circDDX17 可能是治疗和诊断前列腺癌的新的潜在治疗或诊断靶点。由于我们的研究还首次表明 LHPP 可能在前列腺癌中作为一种抗癌基因发挥作用,因此这一发现可能对这种疾病的治疗具有广泛的意义。