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沉默非平滑肌细胞染色体相关多肽G可抑制肝癌细胞增殖并诱导其凋亡。

Silencing non-SMC chromosome-associated polypeptide G inhibits proliferation and induces apoptosis in hepatocellular carcinoma cells.

作者信息

Liu Kaikun, Li Yumin, Yu Bo, Wang Furong, Mi Taiyu, Zhao Yongxun

机构信息

a The Second Clinical Medical School of Lanzhou University, Lanzhou, Gansu Province, 730030; China.

b Department of Surgical Oncology, The Second Hospital of Lanzhou, Lanzhou, Gansu Province, 730000; China.

出版信息

Can J Physiol Pharmacol. 2018 Dec;96(12):1246-1254. doi: 10.1139/cjpp-2018-0195. Epub 2018 Aug 8.

Abstract

The present study was designed to investigate the significance of non-structural maintenance of chromosomes (non-SMC) chromosome-associated polypeptide G (NCAPG), a subunit of condensin complex I, in the development of hepatocellular carcinoma (HCC). NCAPG protein expression in human HCC and paracancerous hepatic tissues were examined using immunohistochemistry, and NCAPG mRNA expression in HCC cell lines were quantified using quantitative RT-PCR. Lentivirus-mediated RNA interference was used to silence NCAPG in HCC cells. Cell proliferation was monitored by MTT assay. Cell colony-forming capacity was measured by colony formation assay. Apoptosis was determined by flow cytometry. The results showed that increased protein expression of NCAPG was found in HCC tissues compared with the matched paracancerous hepatic tissues. At the mRNA level, increased expression of NCAPG was found in HCC cells as opposed to the normal hepatocytes. Silencing of NCAPG in BEL-7404 and SMMC-7721 cells led to decreased cell proliferation and increased apoptosis. These changes were associated with increased mRNA expressions of P53, P27, and Bad, but decreased mRNA expression of EGFR, Akt, survivin, and JNK. NCAPG might play an oncogenic role in the development of liver cancer. Further studies to clarify its role and underlying mechanisms in the development of liver cancer are warranted.

摘要

本研究旨在探讨凝聚素复合体I的一个亚基——非结构性染色体维持蛋白(non-SMC)染色体相关多肽G(NCAPG)在肝细胞癌(HCC)发生发展中的意义。采用免疫组织化学法检测人HCC组织和癌旁肝组织中NCAPG蛋白表达,运用定量逆转录聚合酶链反应(qRT-PCR)对HCC细胞系中NCAPG mRNA表达进行定量分析。利用慢病毒介导的RNA干扰技术使HCC细胞中的NCAPG沉默。通过MTT法监测细胞增殖情况。采用集落形成试验检测细胞集落形成能力。运用流式细胞术测定细胞凋亡情况。结果显示,与配对的癌旁肝组织相比,HCC组织中NCAPG蛋白表达增加。在mRNA水平上,与正常肝细胞相比,HCC细胞中NCAPG表达增加。BEL-7404和SMMC-7721细胞中NCAPG沉默导致细胞增殖减少,凋亡增加。这些变化与P53、P27和Bad的mRNA表达增加有关,但与表皮生长因子受体(EGFR)、蛋白激酶B(Akt)、生存素和c-Jun氨基末端激酶(JNK)的mRNA表达减少有关。NCAPG可能在肝癌发生发展中发挥致癌作用。有必要进一步研究以阐明其在肝癌发生发展中的作用及潜在机制。

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