关键词: invasion microRNA migration prognosis prostate cancer

Mesh : Male Humans Fibroblast Growth Factor 2 / genetics MicroRNAs / genetics Prostatic Neoplasms / genetics diagnosis RNA, Messenger Gene Expression Regulation, Neoplastic Dual-Specificity Phosphatases / genetics Glucose Transporter Type 5 / genetics

来  源:   DOI:10.18632/aging.205213   PDF(Pubmed)

Abstract:
Prostate cancer (PC) is a common urinary system malignancy, and advanced PC patients had a poor prognosis due to recurrence or distant metastasis. Therefore, it\'s imperative to reveal more details in tumorigenesis and prognosis of PC patients.
The miRNA and mRNA expression profile data of 485 PC patients were obtained from The Cancer Genome Atlas database. The univariate Cox regression was applied to screen miRNAs relating to prognosis of PC. Then miRTarBase was used to predict target mRNAs of miRNAs. The hsa-mir-503/hsa-mir-1247 knockdown in 22RV1 cells was established to evaluate the effect of these two miRNAs on tumor cell migration and invasion ability. Flow cytometry was used to detect the effect of hsa-mir-503/hsa-mir-1247 knockdown on 22RV1 apoptosis rate.
Univariate Cox regression analysis identified hsa-mir-503 as a poor and hsa-mir-1247 as a favorable prognostic marker. Totally 649 target mRNAs were screened, among which DUSP19, FGF2, and SLC2A5 had a negative correlation with hsa-mir-503, while FGF2 and VSTM4 had a positive correlation with hsa-mir-1247. In 22RV1 cells, hsa-mir-503 was up-regulated, and hsa-mir-1247 was down-regulated. hsa-mir-503 knockdown attenuated the migration and invasion of 22RV1 cells, while hsa-mir-1247 knockdown exhibited the opposite effect. In addition, hsa-mir-503 knockdown promoted 22RV1 cell apoptosis. hsa-mir-1247 overexpression significantly inhibited the tumor growth of PC in vivo.
Herein, we demonstrated that hsa-mir-503 and hsa-mir-1247 could serve as new prognostic markers of PC, and hsa-mir-1247 had great potential to inhibit PC progression by suppressing the migration and invasion ability in vitro and in vivo.
摘要:
背景:前列腺癌(PC)是一种常见的泌尿系统恶性肿瘤,晚期PC患者因复发或远处转移而预后不良。因此,揭示PC患者肿瘤发生和预后的更多细节势在必行。
方法:从癌症基因组图谱数据库获得485名PC患者的miRNA和mRNA表达谱数据。应用单变量Cox回归筛选与PC预后相关的miRNA。然后使用miRTarBase预测miRNA的靶mRNA。在22RV1细胞中建立hsa-mir-503/hsa-mir-1247敲低,以评估这两种miRNA对肿瘤细胞迁移和侵袭能力的影响。流式细胞术检测hsa-mir-503/hsa-mir-1247敲低对22RV1凋亡率的影响。
结果:单变量Cox回归分析确定hsa-mir-503为不良预后指标,hsa-mir-1247为良好预后指标。共筛选了649个靶mRNA,其中DUSP19,FGF2和SLC2A5与hsa-mir-503呈负相关,而FGF2和VSTM4与hsa-mir-1247呈正相关。在22RV1单元格中,hsa-mir-503上调,hsa-mir-1247被下调。hsa-mir-503敲低减弱22RV1细胞的迁移和侵袭,而hsa-mir-1247敲低表现出相反的效果。此外,hsa-mir-503敲低促进22RV1细胞凋亡。hsa-mir-1247过表达显著抑制体内PC的肿瘤生长。
结论:此处,我们证明hsa-mir-503和hsa-mir-1247可以作为新的PC预后标志物,hsa-mir-1247具有通过抑制体内外迁移和侵袭能力来抑制PC进展的巨大潜力。
公众号