SFPQ在肝细胞癌的表达及其对细胞增殖与细胞周期的影响
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涂康生, Email: tks0912@foxmail.com

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国家自然科学基金资助项目(81773123)。


Expression of SFPQ in hepatocellular carcinoma and its effect on cell proliferation and cell cycle
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    摘要:

    目的:探讨脯氨酸、谷氨酰胺剪接因子(SFPQ)在肝细胞癌(HCC)中的表达及作用。
    方法:采用实时定量PCR及Western blot检测HCC患者的癌组织和对应癌旁组织SFPQ mRNA及蛋白表达。采用TCGA和GEO数据库分析正常肝组织及HCC组织中SFPQ的表达丰度差异;采用TCGA数据库分析SFPQ表达与HCC患者临床分期、病理分级以及患者生存期的关系以及与增殖基因PCNA、Ki-67和周期蛋白CCNE1、CDK2的相关性。观察敲低HCC细胞株HepG2及Hep3B中SFPQ的表达后增殖能力与细胞周期的变化。
    结果:组织标本分析结果显示,SFPQ mRNA及蛋白表达水平在HCC组织中明显高于癌旁组织(均P<0.05)。数据库分析结果显示,HCC组织中SFPQ mRNA表达丰度明显高于正常肝组织,且患者临床分期及病理学分级越高,SFPQ mRNA水平越高,高表达SFPQ的患者的总生存率明显降低,SFPQ mRNA表达与PCNA、Ki-67、CCNE1、CDK2的表达均呈明显正相关(均P<0.05)。敲低SFPQ表达后,HepG2及Hep3B细胞的增殖能力明显减弱,并出现明显G1期阻滞(均P<0.05)。
    结论:SFPQ在HCC中表达升高,升高的SFPQ可通过调节HCC细胞周期,促进HCC细胞的增殖,加速肿瘤进展。

    Abstract:

    Objective: To investigate the expression of splicing factor proline- and glutamine-rich (SFPQ) in hepatocellular carcinoma (HCC) and its actions.
    Methods: The expression levels of SFPQ mRNA and protein in tumor tissues and their adjacent tissues were determined by real-time quantitative PCR and Western blot. The difference in SFPQ mRNA abundance between normal liver tissue and HCC tissue were analyzed by using TCGA and GEO database. The relations of SFPQ mRNA level with the clinical stage, histopathological grade and survival time of HCC patients as well as the correlation of the SFPQ mRNA with the proliferation gene PCNA and Ki-67, and cell cycle protein CCNE1 and CDK2 were analyzed by using TCGA database. The changes in proliferation and cell cycle in HCC HepG2 and Hep3B cells after SFPQ knock down were observed.
    Results: The results of tissue sample analysis showed that the expression levels of both SFPQ mRNA and protein were significantly higher in HCC tissue than those in the adjacent tissue (both P<0.05). The results of database analysis showed that the SFPQ mRNA abundance in HCC tissue was significantly higher than that in normal liver tissue, SFPQ mRNA level was increased with the increase of histopathological grade and the progression of clinical stage, the survival rate was significantly reduced in patients with high SFPQ mRNA expression, and SFPQ mRNA expression was positively correlated with the expressions of PCNA, Ki-67, CCNE1 and CDK2 (P<0.05). In both HepG2 and Hep3B cells after SFPQ knockdown, the proliferative abilities were significantly decreased with significant G1 phase arrest (all P<0.05).
    Conclusion: SFPQ expression is increased in HCC, and the increased SFPQ may accelerate HCC progression via regulating cell cycle and promoting proliferation of the HCC cells.

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陈云茹, 丹增措姆, 白文东, 李青, 涂康生. SFPQ在肝细胞癌的表达及其对细胞增殖与细胞周期的影响[J].中国普通外科杂志,2019,28(1):49-57.
DOI:10.7659/j. issn.1005-6947.2019.01.007

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  • 收稿日期:2018-08-29
  • 最后修改日期:2018-12-13
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  • 在线发布日期: 2019-01-15