THAP11 Functions as a Tumor Suppressor in Gastric Cancer through Regulating c-Myc Signaling Pathways

THAP11 Functions as a Tumor Suppressor in Gastric Cancer through Regulating c-Myc Signaling Pathways
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THAP11 通过调节 c-Myc 信号通路发挥胃癌肿瘤抑制剂的作用

DOI:
10.1155/2020/7838924
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发表时间:
2020-08
影响因子:
--
通讯作者:
Han Jiming
Han Jiming
中科院分区:
生物学3区
文献类型:
--
作者:
Zhang Jing;Zhang Huahua;Shi Haiyan;Wang Fenghui;Du Juan;Wang Yu;Wei Yameng;Xue Wanjuan;Li Dan;Feng Yun;Yan Jing;Gao Yi;Li Jia;Han Jiming

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我们的目的是研究THAP11 (thanatos-associated protein - 11)在胃癌中的作用及其调控机制。采用qRT-PCR和Western blot分析51对胃癌组织及相应癌旁组织中THAP11的表达。THAP11过表达或敲低后,在MKN-45细胞中检测细胞增殖、细胞周期和细胞凋亡。我们发现THAP11在GC组织和GC细胞系中显著下调。功能上,THAP11过表达可显著抑制细胞生长,诱导G1/G0细胞周期阻滞,促进MKN-45细胞凋亡,而THAP11沉默可促进细胞生长,增加DNA合成,抑制细胞凋亡。此外,THAP11负性调控c-Myc的表达,降低cyclinD1蛋白表达,增加p27和p21蛋白表达水平。我们还发现THAP11诱导的细胞生长抑制通过c-Myc过表达得以恢复,进一步证实THAP11通过c-Myc途径抑制胃癌细胞生长。THAP11在胃癌中作为细胞生长抑制因子,可能通过负调控c-Myc通路发挥作用。
We aim to investigate the role of THAP11 (thanatos-associated protein11) in gastric cancer and its regulation mechanisms. THAP11 expression was analyzed in 51 pairs of GC tissues and the corresponding paracancerous tissues by qRT-PCR and Western blot. After THAP11 was overexpressed or knocked-down, cell proliferation, cell cycle, and apoptosis were detected in MKN-45 cells. We found that THAP11 was significantly downregulated in GC tissues and GC cell lines. Functionally, THAP11 overexpression markedly inhibited cell growth, induced G1/G0 cell-cycle arrest, and promoted cell apoptosis of MKN-45 cells, while silencing of THAP11 led to increased cell growth, increased DNA synthesis, and inhibited apoptosis. In addition, THAP11 negatively regulated the expression of c-Myc, decreased cyclinD1 protein, and increased p27 and p21 protein levels. We also found cell growth suppression induced by THAP11 was rescued by c-Myc overexpression, further confirming that THAP11 suppresses gastric cancer cell growth via the c-Myc pathway. THAP11 acts as a cell growth suppressor and exerts its role possibly through negatively regulating c-Myc pathway in gastric cancer.
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