Luo Bingfeng, Yuan Yuan, Zhu Yifei, Liang Songwu, Dong Runan, Hou Jian, Li Ping, Xing Yaping, Lu Zhenquan, Lo Richard, Kuang Guan-Ming
Division of Urology, Department of Surgery, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China.
Department of Pathology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China.
Front Oncol. 2022 Sep 6;12:988794. doi: 10.3389/fonc.2022.988794. eCollection 2022.
To investigate the effects of miRNA-145-5p on the tumor development and progression of prostate cancer (Pca) bone metastasis.
Levels of miRNA-145-5p were assessed by real-time quantitative PCR in PC3 (bone metastatic Pca cells), 22RV1 (non-metastatic Pca cells), RWPE-1 (non-cancerous prostate epithelial cells) and Pca tissues collected from patients with and without bone metastases. The impact of miRNA-145-5p on cell proliferation was tested by CCK8 assay, colony formation assay and flow cytometric cell cycle analysis. Effects on invasion and migration of PC3 cells were determined by Transwell and wound healing assays. Western blotting, enzyme-linked immunosorbent assay, and flow cytometry apoptosis analyses were also performed to assess roles in metastasis.
Levels of miRNA-145-5p were decreased in Pca bone metastases and miRNA-145-5p inhibited cell proliferation, migration and invasion. miRNA-145-5p inhibited the expression of basic fibroblast growth factor (bFGF), insulin-like growth factor (IGF) and transforming growth factor-β (TGF-β) in PC3 cells. miR-145-5p increased the expression of the epithelial marker E-cadherin and reduced the expression of matrix metalloproteinase 2 and 9 (MMP-2 and MMP-9). It was found that miRNA-145-5p mediated the epithelial-mesenchymal transition (EMT) and induced apoptosis.
miRNA-145-5p negatively regulated the EMT, inhibited Pca bone metastasis and promoted apoptosis in Pca bone metastasis. Mimicry of miRNA-145-5p action raises the possibility of a novel target for treating Pca with bone metastases.
探讨微小RNA-145-5p（miRNA-145-5p）对前列腺癌（Pca）骨转移肿瘤发生发展及进程的影响。
采用实时定量聚合酶链反应检测PC3（骨转移性Pca细胞）、22RV1（非转移性Pca细胞）、RWPE-1（非癌性前列腺上皮细胞）以及来自有或无骨转移患者的Pca组织中miRNA-145-5p的水平。通过细胞计数试剂盒8法、集落形成试验和流式细胞术细胞周期分析检测miRNA-145-5p对细胞增殖的影响。采用Transwell试验和伤口愈合试验确定其对PC3细胞侵袭和迁移的影响。还进行了蛋白质免疫印迹法、酶联免疫吸附测定和流式细胞术凋亡分析以评估其在转移中的作用。
Pca骨转移中miRNA-145-5p水平降低，且miRNA-145-5p抑制细胞增殖、迁移和侵袭。miRNA-145-5p抑制PC3细胞中碱性成纤维细胞生长因子（bFGF）、胰岛素样生长因子（IGF）和转化生长因子-β（TGF-β）的表达。miR-145-5p增加上皮标志物E-钙黏蛋白的表达并降低基质金属蛋白酶2和9（MMP-2和MMP-9）的表达。发现miRNA-145-5p介导上皮-间质转化（EMT）并诱导凋亡。
miRNA-145-5p对EMT起负向调节作用，抑制Pca骨转移并促进Pca骨转移中的细胞凋亡。模拟miRNA-145-5p的作用为治疗骨转移性Pca提供了新靶点的可能性。
