The RNA binding protein tristetraprolin down-regulates autophagy in lung adenocarcinoma cells
The RNA binding protein tristetraprolin down-regulates autophagy in lung adenocarcinoma cells
复制标题
RNA结合蛋白tristetraprolin下调肺腺癌细胞的自噬
DOI：
10.1016/j.yexcr.2018.03.028
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发表时间：
2018-06-01
影响因子：
3.7
通讯作者：
Xu, Li
中科院分区：
文献类型：
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作者：
Dong, Fei;Li, Cen;Xu, Li
Tristetraprolin（TTP）是最著名的RNA结合锌指蛋白，在加速mRNA降解中起重要作用。越来越多的研究报道TTP作为抑癌基因在多种肿瘤中发挥作用，但其作用机制尚不清楚。在目前的研究中，我们发现TTP过表达降低肺腺癌细胞的增殖和增加细胞死亡，细胞周期停滞在S期。值得注意的是，TTP过表达改变了细胞自噬，而不是直接诱导细胞凋亡。我们的研究表明，TTP过表达对凋亡相关基因没有影响，但降低了自噬相关基因的表达，包括Beclin 1和LC 3 II。通过mGFP-RFP-LC 3腺病毒构建体感染评估的自噬通量水平已被TTP过表达阻断。透射电镜观察到自噬泡数量随TIP表达上调而减少。我们的研究结果首次表明，TTP通过细胞自噬途径抑制肺癌细胞的增殖并增加细胞死亡。我们的研究为TTP作为肿瘤抑制因子的作用提供了一个新的视角，为肿瘤治疗提供了新的靶点。
Tristetraprolin (TTP) is the most well-known member of RNA-binding zinc-finger protein that play a significant role in accelerating mRNA decay. Increasingly studies have reported that TTP was functioned as a tumor suppressor gene in several types of carcinomas, while its underlying mechanism is not clear yet. In the current study, we found that TTP overexpression decreased cell proliferation and increased cell death in lung adenocarcinoma cells, with the cell cycle arrest at the S phase. Remarkably, instead of inducing cell apoptosis directly, TTP overexpression alters cell autophagy. Our studies demonstrate that TTP overexpression has no effect on apoptosis related genes, but decreases the expression of autophagy-related genes, including Beclin 1 and LC3II. The level of autophagy flux assessed by infection with the mGFP-RFP-LC3 adenovirus construction has been blocked by TTP overexpression. Moreover, the autophagic vacuoles number detected by transmission electron micro-scopy decreased with TIP expression up-regulation. Our results indicate, for the first time, that TTP suppresses cell proliferation and increases cell death through cell autophagy pathway in lung cancer cells. Our study provides a new angle of view for TTP function as a tumor suppressor which could be targeted in tumor treatment.