Sirtuin 6 plays an oncogenic role and induces cell autophagy in esophageal cancer cells
Sirtuin 6 plays an oncogenic role and induces cell autophagy in esophageal cancer cells
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Sirtuin 6 在食管癌细胞中发挥致癌作用并诱导细胞自噬
DOI：
10.1177/1010428317708532
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发表时间：
2017-06-27
期刊：
影响因子：
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通讯作者：
Yang, Qingyuan
中科院分区：
文献类型：
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作者：
Huang, Nan;Liu, Zhiwei;Yang, Qingyuan
Sirtuin 6是sirtuin家族的成员之一，通过对靶基因启动子H3 K9（组蛋白H3赖氨酸9）和H3 K56（组蛋白H3赖氨酸）的脱乙酰化，参与抑制低氧诱导因子1 α和MYC的转录活性，从而抑制有氧糖酵解和细胞生长，被认为是一种肿瘤抑制因子。然而，最近有报道称，其表达在一系列肿瘤中高度升高，包括前列腺癌、乳腺癌和非小细胞肺癌，表明沉默调节蛋白6以细胞/肿瘤类型特异性方式在致瘤性中发挥双重作用。据我们所知，sirtuin 6在食管癌细胞中的生物学作用仍然被低估。在这项研究中，定量逆转录聚合酶链反应和免疫组织化学分析的数据显示，sirtuin 6在食管鳞状肿瘤组织中显着过表达。此外，它的上调与临床特征，如性别，病理，肿瘤淋巴结转移，细胞分化密切相关。随后的生物学试验表明，它能促进食管癌细胞的增殖，并诱导抗凋亡关键因子Bcl 2的表达。此外，使用广泛认可的自噬生物标志物LC 3 II/I的比率，我们表明它明显诱导细胞自噬，这通过自噬通量测定进一步证实。此外，从Western印迹分析和免疫沉淀分析的结果显示，sirtuin 6特异性地与ULK 1相互作用，并通过抑制其上游因子哺乳动物雷帕霉素靶活性来正向调节其活性。总之，我们的研究揭示了sirtuin 6在食管癌细胞中的关键功能，并提供了支持基于sirtuin 6的食管癌细胞患者个性化治疗的证据。
Sirtuin 6, a member of sirtuin family, is generally regarded as a tumor suppressor as it participates in suppressing hypoxia-inducible factor 1 alpha and MYC transcription activity by deacetylating H3K9 (histone H3 lysine 9) and H3K56 (histone H3 lysine) at promoters of target genes, leading to the aerobic glycolysis inhibition and cell growth suppression. However, its expression has recently been reported to be highly elevated in a series of tumors, including prostate cancer, breast cancer, and non-small cell lung cancer, indicating that sirtuin 6 plays dual roles in tumorigenicity in a cell/tumor type-specific manner. To our knowledge, the biological roles of sirtuin 6 in esophageal cancer cells have still been underestimated. In the study, data from quantitative reverse transcriptase polymerase chain reaction-based assays and immunohistochemical assays revealed that sirtuin 6 was remarkably overexpressed in esophageal squamous tumor tissues. Moreover, its upregulation was closely related with clinical features, such as gender, pathology, tumor-node-metastasis, and cell differentiation. Subsequently, the biological tests showed that it promoted cell proliferation and induced the expression of Bcl2, a key anti-apoptotic factor, in esophageal carcinoma cells. Moreover, using the ratio of LC3II/I, a widely recognized autophagy biomarker, we showed that it apparently induced cell autophagy, which was further confirmed by the autophagy flux assays. In addition, results from western blotting assays and immunoprecipitation assays displayed that sirtuin 6 specifically interacted with ULK1 and positively regulated its activity by inhibiting its upstream factor mammalian target of rapamycin activity. In summary, our studies shed insights into the crucial functions of sirtuin 6 in esophageal carcinoma cells and provide evidence supporting sirtuin 6-based personalized therapies in esophageal carcinoma cell patients.