CTNNA1在肝细胞癌中的表达及其对肝癌细胞恶性生物学行为的影响

Expression of CTNNA1 in hepatocellular carcinoma and its impact on the malignant biological behavior of hepatocellular carcinoma cells

  • 摘要: 目的:分析CTNNA1在肝细胞癌(hepatocellular carcinoma,HCC)中的表达及其预后价值,并探讨CTNNA1对肝癌细胞恶性生物学行为的影响。方法:利用公共数据库以及临床标本分析CTNNA1在HCC中的表达水平及其与患者预后的相关性。采用蛋白质免疫印迹(western blotting)法检测肝癌细胞系Huh7、SK-HEP1、LM3、SNU449、MHCC-97H中CTNNA1蛋白表达。利用慢病毒载体转染,在SNU449细胞中过表达CTNNA1基因,小发夹RNA(short hairpin RNA,shRNA)敲低Huh7和MHCC-97H细胞CTNNA1基因。采用细胞计数试剂盒(CCK-8)、平板克隆实验、细胞划痕实验、Transwell迁移和侵袭实验检测过表达及敲低细胞的增殖、迁移、侵袭情况。结果:UALCAN和GEPIA数据库分析结合临床样本验证结果提示,与癌旁组织相比,HCC患者癌组织中CTNNA1 mRNA和蛋白表达上调,且与患者不良预后相关(P<0.05)。与对照组相比,SNU449细胞中过表达CTNNA1后,HCC细胞增殖、迁移、侵袭能力增强,Huh7和MHCC-97H细胞中敲低CTNNA1表达后,HCC细胞增殖、迁移、侵袭能力减弱(均P<0.05)。结论:CTNNA1在HCC中的表达上调,且其高表达与疾病预后不良密切相关,CTNNA1可能是肝癌潜在的预后生物学标志物及治疗靶标。

     

    Abstract: Objective: To analyze the expression and prognostic value of CTNNA1 in hepatocellular carcinoma(HCC), and to explore the impact of CTNNA1 on the malignant biological behavior of HCC cells. Methods: Public databases and clinical specimens were utilized to analyze the expression level of CTNNA1 in HCC and its correlation with patient prognosis. Western blotting was used to detect the expression of CTNNA1 protein in HCC cell lines including Huh7, SK-HEP1, LM3, SNU449, and MHCC-97H. Lentiviral vectors were used to overexpress the CTNNA1 gene in SNU449 cells, and short hairpin RNA(shRNA) was applied to knock down CTNNA1 in Huh7 and MHCC-97H cells. Cell counting kit-8(CCK-8) assay, plate colony formation assay, cell scratch assay, and Transwell migration and invasion assays were used to detect the proliferation, migration and invasion abilities of cells with CTNNA1 overexpression and knockdown. Results: The analysis of UALCAN and GEPIA databases, combined with clinical sample validation, indicated that compared with adjacent normal tissues, the mRNA and protein expression of CTNNA1 were upregulated in HCC cancer tissues, which was associated with poor patient prognosis(P<0.05). Compared with the control group, the proliferation, migration and invasion abilities of HCC cells were significantly enhanced after CTNNA1 overexpression in SNU449 cells. Conversely, knockdown of CTNNA1 expression in Huh7 and MHCC-97H cells markedly weakened these malignant biological abilities(P<0.05). Conclusion: CTNNA1 is upregulated in HCC, and its high expression is closely correlated with poor prognosis. CTNNA1 may serve as a potential prognostic biomarker and therapeutic target for HCC.

     

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