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长链非编码RNA-PVT1促进肾癌细胞的迁移和转移

Long non-coding RNA-PVT1 promotes migration and metastasis of renal carcinoma cells

    摘要
  • 摘要:
    目的 探讨长链非编码RNA-PVT1(Lnc-PVT1)在透明细胞肾细胞癌(ccRCC)中的表达水平及临床意义。
    方法 收集69对ccRCC组织和癌旁正常组织。采用实时荧光定量聚合酶链反应(qRT-PCR)检测Lnc-PVT1在ccRCC中的表达水平。应用RNA原位杂交(RISH)技术测定ccRCC中Lnc-PVT1阳性表达情况。采用Transwell实验分析ccRCC细胞迁移的数目变化。通过生物信息学预测Lnc-PVT1和微小RNA-145 (miR-145)的下游靶基因, 并通过实验加以验证。采用Rescue回复实验分析Lnc-PVT1对miR-145/基质金属蛋白酶-9(MMP9)通路和迁移的影响。
    结果 qRT-PCR结果显示, Lnc-PVT1在ccRCC组织和细胞中表达水平升高(P < 0.05)。RISH实验提示, Lnc-PVT1在ccRCC组织中呈阳性表达。ccRCC组织Lnc-PVT1阳性率为73.91%(51/69), 高于癌旁正常组织的14.49% (10/69), 差异有统计学意义(χ2=4.128, P < 0.05)。Lnc-PVT1的阳性表达与ccRCC病理分级和淋巴结转移相关(P < 0.05), 而与患者年龄、性别、肿瘤大小和TNM分期无关(P>0.05)。Transwell迁移实验结果表明，过表达Lnc-PVT1促进ccRCC细胞迁移能力，降低Lnc-PVT1表达抑制ccRCC细胞迁移能力(P < 0.05)。miR-145是Lnc-PVT1调控的靶基因; miR-145下游直接靶基因是MMP9。Lnc-PVT1能抑制miR-145表达，促进MMP9蛋白表达。
    结论 Lnc-PVT1通过miR-145/MMP9通路促进肾癌细胞的迁移和转移，或可为治疗转移性肾细胞癌提供可能的分子靶点和依据。

     

    Abstract:
    Objective To investigate the expression level and clinical significance of long non-coding RNA-PVT1 (Lnc-PVT1) in clear cell renal cell carcinoma (ccRCC).
    Methods Sixty-nine pairs of ccRCC tissues and adjacent normal tissues were collected. Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression level of Lnc-PVT1 in ccRCC. RNA in situ hybridization (RISH) was used to determine the positive expression of Lnc-PVT1 in ccRCC. Transwell assay was used to analyze the number of cell migration in ccRCC. The downstream target genes of Lnc-PVT1 and microRNA-145 (miR-145) were predicted by bioinformatics and were verified by experiments. The effects of Lnc-PVT1 on miR-145/matrix metalloproteinase-9 (MMP9) pathway and migration were analyzed by Rescue recovery experiment.
    Results The results of qRT-PCR showed that the expression level of Lnc-PVT1 in ccRCC tissues and cells was increased (P < 0.05). RISH assay indicated that Lnc-PVT1 was positively expressed in ccRCC tissue. The positive rate of Lnc-PVT11 in ccRCC tissue was 73.91% (51/69), which was higher than 14.49% of adjacent normal tissues (10/69), the difference was statistically significant (χ2=4.128, P < 0.05). The positive expression of Lnc-PVT1 was correlated with ccRCC pathological grade and lymph node metastasis (P < 0.05), but had no correlations with patient age, sex, tumor size and TNM stage (P>0.05). The results of Transwell migration experiment showed that overexpression of Lnc-PVT1 promoted the migration ability of ccRCC cells, and decreased expression of Lnc-PVT1 inhibited the migration ability of ccRCC cells (P < 0.05). The miR-145 was a target gene regulated by Lnc-PVT1; the downstream direct target gene of miR-145 was MMP9. Lnc-PVT1 could inhibit the expression of miR-145 and promote the expression of MMP9 protein.
    Conclusion Lnc-PVT1 promotes migration and metastasis of renal cancer cells through the miR-145/MMP9 pathway. This study may provide a possible molecular target and basis for the treatment of metastatic renal cell carcinoma.

     

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