Yang Jun, Liu Jingshu, Zhao Shaozhen, Tian Fang
Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China.
Tianjin University of Traditional Chinese Medicine, Tianjin, China.
Mol Ther Nucleic Acids. 2020 Jun 5;20:111-116. doi: 10.1016/j.omtn.2020.02.002. Epub 2020 Feb 11.
N-methyladenosine (mA) 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 mA in the DC pathogenesis is poorly understood. In present research, we performed the mA-RNA immunoprecipitation sequencing (MeRIP-Seq) analysis and detected the mA 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 mA 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 mA modification for DC.
N-甲基腺苷（mA）是真核生物中最普遍的信使核糖核酸修饰。糖尿病性白内障（DC）由糖尿病中的高血糖（HG）引起。然而，mA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mA-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（HLEC）中的mA修饰谱。结果显示，在DC组织标本和HG诱导的HLEC中，类甲基转移酶3（METTL3）上调。此外，HG诱导的HLEC中总mA修饰水平更高。在功能上，敲低METTL3可促进HG诱导的HLEC增殖并抑制其凋亡。MeRIP-Seq分析表明，细胞间黏附分子-1（ICAM-1）可能是METTL3的靶点。机制上，METTL3靶向ICAM-1的3'非翻译区以稳定mRNA稳定性。总之，本研究确定了METTL3在HG诱导的HLEC中的调控作用，为DC的mA修饰提供了潜在的见解。
