Valera Vladimir A, Parra-Medina Rafael, Walter Beatriz A, Pinto Peter, Merino Maria J
Urologic Oncology Branch, National Cancer Institute, National Institutes of Health. Bethesda MD.
Translational Surgical Pathology Section, Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda MD.
J Cancer. 2020 Apr 7;11(14):4106-4114. doi: 10.7150/jca.37842. eCollection 2020.
MicroRNAs (miRNAs) are small, non-coding RNA molecules with multiple roles in many biological processes. Few studies have shown the molecular characteristics in younger prostate cancer (PCa) patients. In this study, we performed miRNA profiling in young PCa (EO-PCa) cases compared with PCa arising in older men (LO-PCa). : Formalin-fixed, paraffin embedded tissue was used. miRNA was extracted for PCR array and NanoString methods. Relative miRNAs expression levels were obtained by comparing young vs older men, and young PCa tumor samples vs normal epithelium. : miRNA profiling showed a different expression pattern in PCa arising in younger men, and young PCa tumoral and its normal counterpart. Nine miRNAs (hsa-miR-140-5p, hsa-miR-146a, hsa-miR-29b, hsa-miR-9, hsa-miR-124-3p, hsa-let-7f-5p, hsa-miR-184, hsa-miR-373, hsa-miR-146b-5p) showed differences in the expression compared to LO-PCa. Fourteen miRNAs were significantly up-regulated (miR-1973, miR-663a, miR-575, miR-93-5p, miR-630, miR-600, miR-494, miR-150-5p, miR-137, miR-25-3p, miR-375, miR-489, miR-888-5p, miR-142-3p), while 9 were found down-regulated (miR-21-5p, miR-363-3p, miR-205-5p, miR-548ai, miR-3195, 145-5p, miR-143-3p, miR-222-3p, miR-221-3p) comparing young PCa tumoral tissue compared to normal counterpart. The higher expression of miR-600 and miR-137 were associated with high Gleason score, extraprostatic extension and lymphatic invasion. : These results suggest that PCa in younger patients has a different expression profile compared to normal tissue and PCa arising in older man. Differentially expressed miRNAs provide insights of molecular mechanisms involve in this PCa subtype.
微小RNA(miRNA)是一类小的非编码RNA分子,在许多生物学过程中发挥多种作用。很少有研究揭示年轻前列腺癌(PCa)患者的分子特征。在本研究中,我们对年轻PCa(早发性PCa,EO-PCa)病例与老年男性发生的PCa(迟发性PCa,LO-PCa)进行了miRNA谱分析。:使用福尔马林固定、石蜡包埋组织。提取miRNA用于PCR阵列和NanoString方法。通过比较年轻男性与老年男性以及年轻PCa肿瘤样本与正常上皮组织,获得相对miRNA表达水平。:miRNA谱分析显示,年轻男性发生的PCa以及年轻PCa肿瘤与其正常对应组织中存在不同的表达模式。9种miRNA(hsa-miR-140-5p、hsa-miR-146a、hsa-miR-29b、hsa-miR-9、hsa-miR-124-3p、hsa-let-7f-5p、hsa-miR-184、hsa-miR-373、hsa-miR-146b-5p)与LO-PCa相比,表达存在差异。与正常对应组织相比,年轻PCa肿瘤组织中有14种miRNA显著上调(miR-1973、miR-663a、miR-575、miR-93-5p、miR-630、miR-600、miR-494、miR-150-5p、miR-137、miR-25-3p、miR-375、miR-489、miR-888-5p、miR-142-3p),9种miRNA下调(miR-21-5p、miR-363-3p、miR-205-5p、miR-548ai、miR-3195、145-5p、miR-143-3p、miR-222-3p、miR-221-3p)。miR-600和miR-137的高表达与高Gleason评分、前列腺外侵犯和淋巴转移相关。:这些结果表明,年轻患者的PCa与正常组织以及老年男性发生的PCa相比,具有不同的表达谱。差异表达的miRNA为该PCa亚型所涉及的分子机制提供了见解。