N6-Methyladenosine METTL3 Modulates the Proliferation and Apoptosis of Lens Epithelial Cells in Diabetic Cataract
N6-Methyladenosine METTL3 Modulates the Proliferation and Apoptosis of Lens Epithelial Cells in Diabetic Cataract
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DOI：
10.1016/j.omtn.2020.02.002
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发表时间：
2020-06-05
影响因子：
8.8
通讯作者：
Tian, Fang
中科院分区：
文献类型：
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作者：
Yang, Jun;Liu, Jingshu;Tian, Fang
n -6-甲基腺苷（m(6)A）是最常见的真核信使RNA修饰。糖尿病性白内障（DC）是由糖尿病患者的高血糖（HG）引起的。然而，m(6)A在DC发病机制中的调控机制尚不清楚。在本研究中，我们进行了m(6)A- rna免疫沉淀测序（MeRIP-Seq）分析，并检测了HG或正常葡萄糖（NG）诱导的人晶状体上皮细胞（HLECs）中的m(6)A修饰谱。结果显示，甲基转移酶样3 （METTL3）在DC组织标本和hg诱导的HLECs中上调。此外，hg诱导的HLECs中总m(6)A修饰水平较高。功能上，METTL3基因敲低可促进HG诱导的HLECs增殖并抑制凋亡，MeRIP-Seq分析显示ICAM-1可能是METTL3的靶点。从机制上讲，METTL3靶向ICAM-1的3' UTR以稳定mRNA的稳定性。总之，本研究确定了METTL3在hg诱导的HLECs中的调控作用，为研究m(6) a修饰对DC的影响提供了潜在的见解。
N-6-methyladenosine (m(6)A) is the most prevalent eukaryotic messenger RNA modification. Diabetic cataract (DC) is caused by high glucose (HG) in diabetes mellitus. However, the regulatory mechanism of m(6)A in the DC pathogenesis is poorly understood. In present research, we performed the m(6)A-RNA immunoprecipitation sequencing (MeRIP-Seq) analysis and detected the m(6)A modification profile in the HG- or normal glucose (NG)-induced human lens epithelial cells (HLECs). Results revealed that methyltransferase-like 3 (METTL3) was upregulated in the DC tissue specimens and HG-induced HLECs. Besides, total m(6)A modification level was higher in the HG-induced HLECs. Functionally, METTL3 knockdown promoted the proliferation and repressed the apoptosis of HLECs induced by HG. MeRIP-Seq analysis revealed that ICAM-1 might act as the target of METTL3. Mechanistically, METTL3 targets the 3' UTR of ICAM-1 to stabilize mRNA stability. In conclusion, this research identified the regulation of METTL3 in the HG-induced HLECs, providing a potential insight of the m(6)A modification for DC.