USP30在肝癌组织和细胞中高表达可促进肝癌的发生发展

    The High Expression of USP30 Promotes Carcinogenesis and Progression of Hepatocellular Carcinoma

    • 摘要:
      目的 探讨泛素特异性肽酶30(ubiquitin-specific protease 30,USP30)在肝细胞癌(hepatocellular carcinoma,HCC)组织和细胞的表达水平及其对HCC细胞增殖、侵袭和迁移的影响。
      方法 利用肿瘤基因组图谱(The Cancer Genome Atlas,TCGA)数据库分析USP30在HCC和癌旁组织中的表达水平及其与TNM分级、临床分期等临床病理参数的相关性;用实时荧光定量逆转录-聚合酶链反应(reverse transcription quantitative real-time polymerase chain reaction,RT-qPCR)和western blot方法验证USP30在5种HCC细胞中的表达情况;用细胞计数(cell counting kit-8,CCK-8)、transwell和划痕实验研究过表达及敲低USP30对HCC细胞增殖、迁移和侵袭能力的影响;采用免疫荧光法确定USP30的亚细胞定位。
      结果 USP30在HCC组织中的表达水平显著高于癌旁组织;高表达USP30与TNM分级和临床分期显著相关;USP30 mRNA和蛋白表达量在5种HCC细胞中均高于正常肝脏细胞;过表达USP30促进HCC细胞的增殖、侵袭和迁移,而敲低USP30则抑制了HCC细胞的增殖、侵袭和迁移;免疫荧光实验表明USP30定位于细胞质。
      结论 USP30在HCC组织和细胞中高表达,高表达的USP30促进HCC细胞的增殖、侵袭和转移,USP30有望作为HCC诊断及治疗的潜在分子靶点。

       

      Abstract:
      Objective To explore the expression of ubiquitin-specific protease 30(USP30)in hepatocellular carcinoma (HCC), and investigate its role in HCC cell proliferation, invasion, and migration.
      Methods The expression differential of USP30 was analyzed in HCC tissues and adjacent tissues from The Cancer Genome Atlas (TCGA) database. Following that, we looked at the correlations of USP30 expression with the clinicopathological characteristics of HCC patients, including TNM and clinical stages. Reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) and western blotting were used to detect the expression of USP30 in 5 HCC cell lines. We assessed the effects of USP30 over-expression and knockdown on proliferation, migration, and invasion of HCC cells with cell counting kit-8 (CCK-8) assay, transwell assay, and wound healing assay. The subcellular localization of USP30 in 293T cells was determined using an immunofluorescence assay.
      Results The expression level of USP30 in HCC tissues was significantly higher than in adjacent tissues and significantly correlated with TNM and clinical stages in HCC. The mRNA and protein expression levels of USP30 were significantly higher in the 5 HCC cell lines than in normal liver cells. Overexpression of USP30 promoted the proliferation, invasion, and migration of HCC cells, while USP30 knockdown produced the opposite effects. Immunofluorescence assay identified subcellular localization of USP30 in the cytoplasm of 293T cells.
      Conclusions USP30 is highly expressed in HCC tissues and cells to promote proliferation and metastasis in HCC cells and may serve as a potential molecular target for diagnosing and treating HCC.

       

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