Department of Urology, Affiliated Sixth People's Hospital, Shanghai JiaoTong University, Shanghai 200233, P.R. China.
Wake Forest Institute for Regenerative Medicine, Winston‑Salem, NC 27157, USA.
Int J Mol Med. 2018 May;41(5):2733-2743. doi: 10.3892/ijmm.2018.3487. Epub 2018 Feb 12.
Pelvic fracture urethral distraction defect (PFUDD) seriously affects the quality of life of patients. At present, there are few effective drug treatments available for PFUDD‑induced urethral stricture, which is associated with fibrosis and scar formation in urethra lumen. Emerging evidence suggests that microRNAs (miRNAs/miRs) may be involved in the regulation of fibrosis, and analysis of miRNA expression profiles in urethral scar and normal urethra tissues may therefore benefit the discovery of novel treatments for urethral stricture with micro invasive procedures. In the present study, miRNA sequencing and quantitative polymerase chain reaction (qPCR) validation using paired scar and normal tissues from patients with PFUDD, and functional analysis of the miRNAs involved in the fibrosis associated signaling pathway was performed. A total of 94 differentially expressed miRNAs were identified in the scar tissue of patients with PFUDD. Among them, 26 miRNAs had significantly altered expression in the scar tissue compared with the normal tissue from the same patient. qPCR validation confirmed that miR‑129‑5p was overexpressed in scar tissue. The TGF‑β pathway‑associated functions of a total of 5 miRNAs (hsa‑miR‑129‑5p, hsa‑miR‑135a‑5p, hsa‑miR‑363‑3p, hsa‑miR‑6720‑3p and hsa‑miR‑9‑5p) were further analyzed, as well as their key molecular targets and functional mechanisms in signaling regulation. To conclude the miRNA sequencing indicated a significantly altered expression of hsa‑miR‑129‑5p, hsa‑miR‑135a‑5p, hsa‑miR‑363‑3p, hsa‑miR‑6720‑3p and hsa‑miR‑9‑5p in patients with PFUDD. These miRNAs and their potential target genes were associated with fibrosis in several diseases, and the data from the present study may help explore potential miRNA targets for future precision treatments for urethral stricture.
骨盆骨折尿道牵张缺损 (PFUDD) 严重影响患者的生活质量。目前,PFUDD 引起的尿道狭窄几乎没有有效的药物治疗方法,这与尿道管腔中的纤维化和瘢痕形成有关。新出现的证据表明,微小 RNA (miRNA/miRs) 可能参与纤维化的调节,因此对 PFUDD 患者尿道瘢痕和正常尿道组织中的 miRNA 表达谱进行分析可能有助于通过微创程序发现治疗尿道狭窄的新方法。在本研究中,对来自 PFUDD 患者的瘢痕组织和正常组织进行 miRNA 测序和定量聚合酶链反应 (qPCR) 验证,并对涉及纤维化相关信号通路的 miRNA 进行功能分析。在 PFUDD 患者的瘢痕组织中鉴定出 94 个差异表达的 miRNA。其中,26 个 miRNA 在瘢痕组织中的表达与同一患者的正常组织相比有明显改变。qPCR 验证证实 miR-129-5p 在瘢痕组织中过表达。进一步分析了总共 5 个 miRNA (hsa-miR-129-5p、hsa-miR-135a-5p、hsa-miR-363-3p、hsa-miR-6720-3p 和 hsa-miR-9-5p) 的 TGF-β 通路相关功能,以及它们在信号调节中的关键分子靶标和功能机制。总之,miRNA 测序表明 PFUDD 患者的 hsa-miR-129-5p、hsa-miR-135a-5p、hsa-miR-363-3p、hsa-miR-6720-3p 和 hsa-miR-9-5p 的表达明显改变。这些 miRNA 及其潜在的靶基因与几种疾病中的纤维化有关,本研究的数据可能有助于探索未来治疗尿道狭窄的潜在 miRNA 靶点。