Department of Nuclear Medicine, Affiliated Hospital of BeiHua University, Jilin, Jilin 132011, P.R. China.
Department of Oncology, Affiliated Hospital of BeiHua University, Jilin, Jilin 132011, P.R. China.
Mol Med Rep. 2018 Jun;17(6):8450-8456. doi: 10.3892/mmr.2018.8910. Epub 2018 Apr 20.
MicroRNA (miRNA)‑145 has been demonstrated to serve a role in several types of tumors, however, the potential molecular mechanism of action of miRNA‑145 in bladder cancer metastasis remains to be elucidated. This study aimed to investigate the potential modulation of miRNA‑145 in bladder carcinoma and elucidate the underlying molecular mechanism. The expression of miRNA‑145 in bladder adenocarcinoma tissues and bladder cancer cells was measured by reverse transcription‑quantitative polymerase chain reaction. miRNA‑145 mimics and inhibitor were transfected into bladder cancer (BC) cells to determine the role of miRNA‑145 on cell motility and invasion measured by wound healing and transwell assays. Luciferase assay was performed to confirm whether N‑cadherin was the direct target of miRNA‑145. Subsequently, expression of N‑cadherin and matrix metalloproteinase‑9 (MMP9) in BC cells were detected by western blot analysis. miRNA‑145 was significantly downregulated cells and tissues from patients with BC, compared with healthy controls. miRNA‑145 markedly inhibited the ability of BC cells to migrate and invade. Furthermore, N‑cadherin was identified as a target of miRNA‑145 in BC cells. MMP9, acting downstream of N‑cadherin, was downregulated in BC cells by miRNA‑145. In the present study, miRNA‑145 suppressed the migration and invasion of BC cells by regulating N‑cadherin. The results of the present study indicated that miRNA‑145 may function as a tumor suppressor and may have a potential to be a diagnostic and predictive biomarker, and a therapeutic target for treatment of BC.
微小 RNA（miRNA）-145 已被证明在多种类型的肿瘤中发挥作用，然而，miRNA-145 在膀胱癌转移中的潜在作用机制仍有待阐明。本研究旨在探讨 miRNA-145 在膀胱癌中的潜在调节作用，并阐明其潜在的分子机制。通过逆转录-定量聚合酶链反应测量膀胱癌腺癌组织和膀胱癌细胞中 miRNA-145 的表达。将 miRNA-145 模拟物和抑制剂转染到膀胱癌（BC）细胞中，通过划痕愈合和 Transwell 测定来确定 miRNA-145 对细胞迁移和侵袭的作用。通过荧光素酶测定来验证 N-钙黏蛋白是否是 miRNA-145 的直接靶标。随后，通过 Western blot 分析检测 BC 细胞中 N-钙黏蛋白和基质金属蛋白酶-9（MMP9）的表达。与健康对照组相比，BC 患者的细胞和组织中 miRNA-145 的表达明显下调。miRNA-145 显著抑制 BC 细胞的迁移和侵袭能力。此外，N-钙黏蛋白被鉴定为 BC 细胞中 miRNA-145 的靶标。MMP9 作为 N-钙黏蛋白的下游因子，在 miRNA-145 作用下在 BC 细胞中下调。在本研究中，miRNA-145 通过调节 N-钙黏蛋白抑制 BC 细胞的迁移和侵袭。本研究结果表明，miRNA-145 可能作为肿瘤抑制因子发挥作用，并有潜力成为膀胱癌诊断和预测生物标志物以及治疗靶点。
