m(6) A methyltransferase METTL3 promotes retinoblastoma progression via PI3K/AKT/mTOR pathway.
m(6) A methyltransferase METTL3 promotes retinoblastoma progression via PI3K/AKT/mTOR pathway.
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m(6)甲基转移酶 METTL3 通过 PI3K/AKT/mTOR 通路促进视网膜母细胞瘤进展
DOI：
10.1111/jcmm.15736
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发表时间：
2020-11
影响因子：
5.3
通讯作者：
Shen H
中科院分区：
文献类型：
--
作者：
Zhang H;Zhang P;Long C;Ma X;Huang H;Kuang X;Du H;Tang H;Ling X;Ning J;Liu H;Deng X;Zou Y;Wang R;Cheng H;Lin S;Zhang Q;Yan J;Shen H
视网膜母细胞瘤是儿童常见的眼内恶性肿瘤。由于RB的预后差，寻求有效的诊断和治疗策略至关重要。研究表明，甲基转移酶样3（Methyltransferase‐like 3，缩写为L3）是一种主要的RNA N（6）-腺苷甲基转移酶，与癌症的发生和发展密切相关。然而，胃L3是否与RB相关仍有待研究。因此，我们研究了胃L3在RB进展的调节中的功能和机制。我们操纵RB细胞中的胃L3表达。分析细胞增殖、凋亡、迁移和侵袭能力。我们还分析了PI 3 K/AKT/mTOR通路成员的表达。最后，我们将皮下异种移植小鼠模型纳入我们的研究。结果表明，RB患者和RB细胞中均高表达胃L3。我们发现，在体外和体内，胃L3敲低降低RB细胞的增殖、迁移和侵袭，而胃L3过表达促进RB进展。此外，PI 3 K/AKT/mTOR通路的两个下游成员P70 S6 K和4 EBP 1受到胃L3的影响。我们的研究表明，在体外和体内，胃L3通过PI 3 K/AKT/mTOR途径促进RB的进展。靶向胃L3/PI 3 K/AKT/mTOR信号传导轴可能是治疗RB的有前景的治疗策略。
Retinoblastoma (RB) is a common intraocular malignancy in children. Due to the poor prognosis of RB, it is crucial to search for efficient diagnostic and therapeutic strategies. Studies have shown that methyltransferase‐like 3 (METTL3), a major RNA N (6)‐adenosine methyltransferase, is closely related to the initiation and development of cancers. Nevertheless, whether METTL3 is associated with RB remains unexplored. Therefore, we investigated the function and mechanisms of METTL3 in the regulation of RB progression. We manipulated METTL3 expression in RB cells. Then, cell proliferation, apoptosis, migration and invasion were analysed. We also analysed the expression of PI3K/AKT/mTOR pathway members. Finally, we incorporated subcutaneous xenograft mouse models into our studies. The results showed that METTL3 is highly expressed in RB patients and RB cells. We found that METTL3 knockdown decreases cell proliferation, migration and invasion of RB cells, while METTL3 overexpression promotes RB progression in vitro and in vivo. Moreover, two downstream members of the PI3K/AKT/mTOR pathway, P70S6K and 4EBP1, were affected by METTL3. Our study revealed that METTL3 promotes the progression of RB through PI3K/AKT/mTOR pathways in vitro and in vivo. Targeting the METTL3/PI3K/AKT/mTOR signalling axis could be a promising therapeutic strategy for the treatment of RB.
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