MiR-4465 directly targets PTEN to inhibit AKT/mTOR pathway-mediated autophagy
MiR-4465 directly targets PTEN to inhibit AKT/mTOR pathway-mediated autophagy
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MiR-4465 直接靶向 PTEN，抑制 AKT/mTOR 通路介导的自噬。
DOI：
10.1007/s12192-018-0946-6
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发表时间：
2019-01-01
影响因子：
3.8
通讯作者：
Wang, Mei
中科院分区：
文献类型：
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作者：
Tao, Zhouteng;Feng, Chenxi;Wang, Mei
自噬在维持细胞功能方面起着重要作用。自噬异常会导致细胞功能障碍，并与许多疾病有关，如肿瘤、免疫缺陷疾病、溶酶体储存障碍和神经退行性疾病。自噬受到精确调控，而PTEN在调控自噬中起着重要作用。作为非编码的小RNA，miRNAs在细胞过程的精细调控中发挥着重要作用。然而，miRNA调控PTEN相关自噬的机制尚未完全阐明。在这项研究中，我们的结果表明，miR-4465显著抑制PTEN的表达，上调磷酸化的AKT，从而通过激活mTOR抑制HEK293、HeLa和SH-SY5Y细胞的自噬。进一步的研究表明，miR-4465通过直接靶向3-UTR，通过转录后调控降低PTEN的mRNA水平。我们的新发现为全面阐明miRNA调控PTEN相关自噬的分子机制提供了有用的线索，也可能为探索miRNAs在PTEN相关疾病治疗中的作用提供一些新的见解。
Autophagy plays an important role in maintaining cell function. Abnormal autophagy leads to cell dysfunction and is associated with many diseases such as tumors, immunodeficiency diseases, lysosomal storage disorders, and neurodegenerative diseases. Autophagy is precisely regulated, and PTEN plays an important role in regulating autophagy. As noncoding small RNAs, miRNAs play an important role in the fine regulation of cellular processes. However, the mechanism of the miRNA regulation of PTEN-related autophagy has not been fully elucidated. In this study, our results showed that miR-4465 significantly inhibited the expression of PTEN, upregulated phosphorylated AKT, and thereby inhibited autophagy by activating mTOR in HEK293, HeLa, and SH-SY5Y cells. Further studies indicated that miR-4465 reduced PTEN mRNA levels through posttranscriptional regulation via directly targeting the 3-UTR. Our novel findings provide useful hints for the comprehensive elucidation of the molecular mechanism of miRNA-regulated PTEN-related autophagy and may also provide some new insights for the exploration of miRNAs in the treatment of PTEN-related diseases.