ZNF32 inhibits autophagy through the mTOR pathway and protects MCF-7 cells from stimulus-induced cell death.
ZNF32 inhibits autophagy through the mTOR pathway and protects MCF-7 cells from stimulus-induced cell death.
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ZNF32 通过 mTOR 途径抑制自噬，并保护 MCF-7 细胞免受刺激诱导的细胞死亡。
DOI：
10.1038/srep09288
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发表时间：
2015-03-19
影响因子：
4.6
通讯作者：
Wei Y
中科院分区：
文献类型：
--
作者：
Li Y;Zhang L;Li K;Li J;Xiang R;Zhang J;Li H;Xu Y;Wei Y;Gao J;Lin P;Wei Y
ZNF 32是最近发现的一种锌指蛋白，其功能尚不清楚。自噬已被证明影响细胞增殖和存活。在这里，我们创新性地显示了ZNF 32对乳腺癌细胞中细胞自噬和自噬相关细胞死亡的影响，并阐明了其潜在的机制。我们研究了ZNF 32表达增加或减少的人癌细胞系中的自噬活性和LC 3 II表达。药理学抑制（雷帕霉素）或活化（EGF）测定用于研究AKT/mTOR途径在该过程中的功能。H2 O2和二酰胺诱导的MCF-7细胞死亡模型用于阐明ZNF 32相关的自噬在乳腺癌细胞死亡中的作用。我们的研究结果表明，在MCF-7细胞中增加ZNF 32表达通过激活AKT/mTOR通路抑制自噬起始，并进一步减少自噬相关的细胞死亡和维持MCF-7细胞存活。相反，通过抑制ZNF 32 siRNA来削弱ZNF 32表达强烈促进自噬，进一步增加自噬相关的细胞死亡。此外，在MCF-7异种移植肿瘤和乳腺癌患者中观察到ZNF 32和自噬之间的相关性。总之，ZNF 32作为一种有效的自噬抑制剂，以保护乳腺癌细胞免受过度刺激诱导的细胞死亡。
ZNF32 is a recently identified zinc finger protein and its functions remain largely unknown. Autophagy has been shown to affect cell proliferation and survival. Here, we innovatively show the effect of ZNF32 on cell autophagy and autophagy-associated cell death in breast carcinoma cells and also elucidate its underlying mechanisms. We examined the autophagic activity and LC3 II expression in human carcinoma cell lines with increased or decreased ZNF32 expression. Pharmacological inhibition (rapamycin) or activation (EGF) assays were used to investigate the function of the AKT/mTOR pathway during this process. H2O2- and diamide-induced MCF-7 cell death models were used to elucidate the role of ZNF32-associated autophagy in breast carcinoma cell death. Our results show that increasing ZNF32 expression in MCF-7 cells inhibits autophagy initiation by activating the AKT/mTOR pathway, and further reduced autophagy-associated cell death and maintained MCF-7 cell survival. Conversely, impairing ZNF32 expression by transfecting ZNF32 siRNA strongly promoted autophagy, further augmenting autophagy-associated cell death. Furthermore, correlations between ZNF32 and autophagy were observed in both MCF-7 xenograft tumors and in breast cancer patients. In conclusion, ZNF32 acts as an effective autophagy inhibitor to protect breast cancer cells from excessive stimulus-autophagy-induced cell death.
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