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原发性纤毛阻滞通过诱导自噬促进肝癌的恶性行为。

Primary Cilia Blockage Promotes the Malignant Behaviors of Hepatocellular Carcinoma via Induction of Autophagy.

机构信息

Division of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

出版信息

Biomed Res Int. 2019 Oct 2;2019:5202750. doi: 10.1155/2019/5202750. eCollection 2019.

Abstract

Primary cilia are organelles protruding from cell surface into environment that function in regulating cell cycle and modulating cilia-related signal. Primary ciliogenesis and autophagy play important roles in tumorigenesis. However, the functions and interactions between primary cilia and autophagy in hepatocellular carcinoma (HCC) have not been reported yet. Here, we aimed to investigate the relationship and function of primary cilia and autophagy in HCC. , we showed that serum starvation stimuli could trigger primary ciliogenesis in HCC cells. Blockage of primary ciliogenesis by IFT88 silencing enhanced the proliferation, migration, and invasion ability of HCC cells. In addition, inhibition of primary cilia could positively regulate autophagy. However, the proliferation, migration, and invasion ability which were promoted by IFT88 silencing could be partly reversed by inhibition of autophagy. , interference of primary cilia led to acceleration of tumor growth and increase of autophagic flux in xenograft HCC mouse models. Moreover, IFT88 high expression or ATG7 low expression in HCC tissues was correlated with longer survival time indicated by the Cancer Genome Atlas (TCGA) analysis. In conclusion, our study demonstrated that blockage of primary ciliogenesis by IFT88 silencing had protumor effects through induction of autophagy in HCC. These findings define a newly recognized role of primary cilia and autophagy in HCC.

摘要

原发性纤毛是从细胞表面突出到环境中的细胞器,在调节细胞周期和调节纤毛相关信号方面发挥作用。原发性纤毛发生和自噬在肿瘤发生中起重要作用。然而,原发性纤毛和自噬在肝细胞癌(HCC)中的功能和相互作用尚未见报道。在这里,我们旨在研究原发性纤毛和自噬在 HCC 中的关系和功能。我们发现,血清饥饿刺激可以触发 HCC 细胞的原发性纤毛发生。IFT88 沉默阻断原发性纤毛发生增强了 HCC 细胞的增殖、迁移和侵袭能力。此外,原发性纤毛的抑制可以正向调节自噬。然而,IFT88 沉默促进的增殖、迁移和侵袭能力可以部分被自噬抑制所逆转。在异种移植 HCC 小鼠模型中,干扰原发性纤毛导致肿瘤生长加速和自噬通量增加。此外,HCC 组织中 IFT88 高表达或 ATG7 低表达与癌症基因组图谱(TCGA)分析所示的生存时间延长相关。总之,我们的研究表明,IFT88 沉默阻断原发性纤毛发生通过诱导 HCC 中的自噬产生促肿瘤作用。这些发现定义了原发性纤毛和自噬在 HCC 中的新作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3888/6791284/ad4068c142a3/BMRI2019-5202750.001.jpg

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