微小RNA-193a-5p在肾细胞癌进展中的作用及机制研究

Role and mechanism of microRNA-193a-5p in progression of renal cell carcinoma

  • 摘要:
      目的  探讨微小RNA-193a-5p(miR-193a-5p)在肾细胞癌(RCC)组织和RCC细胞系中的表达情况及其对RCC细胞系增殖、迁移、侵袭的影响,并探讨miR-193a-5p靶基因原钙黏连蛋白12(PCDHA12)在RCC中的作用。
      方法  采用实时荧光定量聚合酶链反应(RT-qPCR)、细胞划痕实验、细胞增殖实验、Transwell实验和流式细胞术检测miR-193a-5p表达水平及其对RCC细胞系的增殖、迁移、侵袭和凋亡的影响情况。通过GEPIA、UALCAN分析PCDH12在RCC中的表达情况和预后价值,并应用GSCALite对PCDHA12及其互作蛋白进行肿瘤通路活性和药物敏感性分析。
      结果  miR-193a-5p在RCC组织和RCC细胞系中呈高表达,且miR-193a-5p在786-O、ACHN细胞系中可促进细胞增殖、迁移和侵袭并抑制细胞凋亡。GEPIA分析发现, PCDHA12在RCC组织中表达下调,并在多个数据库中得到验证,且PCDHA12低表达与RCC患者低生存率相关。肿瘤通路活性分析结果显示, PCDHA12及其互作蛋白与RCC细胞的周期进程呈显著负相关,同时激活了EMT通路、Hormone ER等通路。药物敏感性分析结果显示, HKR1和ZCCHC5是药物筛选的潜在生物标志物。
      结论  miR-193a-5p在RCC组织中高表达,并促进RCC细胞系的侵袭、迁移,抑制RCC细胞的凋亡。PCDHA12在RCC组织中低表达,可预测RCC患者的预后。miR-193a-5p可能通过抑制PCDHA12影响RCC细胞周期进程而促进RCC的进展,这为进一步研究miR-193a-5p促进RCC进展的作用机制奠定了基础。

     

    Abstract:
      Objective  To explore the expressions of microRNA-193a-5p(miR-193a-5p) in renal cancer (RCC)tissues and RCC cell lines and their effects on cell proliferation, migration and invasion in RCC cell lines, and the role of miR-193a-5p target gene protocadherin-alpha 12 (PCDHA12) in RCC.
      Methods  Real-time fluorescent quantitative PCR(RT-qPCR), cell scratch test, cell proliferation test, transwell test and flow cytometry were used to detect the expression level of miR-193a-5p and its effects on the proliferation, migration, invasion and apoptosis of RCC cell line. The expression and prognostic value of PCDHA12 in RCC were analyzed via analysis of GEPIA and UALCAN, and GSCALite was used to analyze the tumor pathway activity, drug sensitivity of PCDHA12 and its interaction protein.
      Results  MiR-193a-5p was highly expressed in RCC tissues and RCC cell lines, and it promoted cell proliferation, migration and invasion and inhibited apoptosis in 786-O and ACHN cell lines. GEPIA analysis found that PCDHA12 was down-regulated in RCC tissue, which was validated in researches in multiple databases. In addition, low expression of PCDHA12 was found to be associated with low survival. As for the activity analysis of tumor pathways, PCDHA12 and its interacting proteins had significant negative correlations with the cycle progression of RCC cells, and they activated EMT pathways, Hormone ER pathways, etc. Drug sensitivity analysis showed that HKR1 and ZCCHC5 were potential biomarkers for drug screening.
      Conclusion  MiR-193a-5p is highly expressed in RCC tissues, promotes the invasion and migration of RCC cell lines and inhibits the apoptosis of RCC cells. PCDHA12 is lowly expressed in RCC tissues, which can predict the prognosis of RCC. MiR-193a-5p promotes the development of RCC by inhibiting PCDHA12 from affecting the RCC cell cycle progression. The results of this study will provide a basis for further study on the role of miR-193a-5p in promoting the progression of RCC.

     

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