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mTOR 信号网络中的长非编码 RNA:生物标志物和治疗靶点。

Long noncoding RNAs in the mTOR signaling network: biomarkers and therapeutic targets.

机构信息

Oncology Department, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 201900, China.

Rutgers University, 604 Allison Road, Piscataway, NJ, 08854, USA.

出版信息

Apoptosis. 2018 Jun;23(5-6):255-264. doi: 10.1007/s10495-018-1453-z.

Abstract

As an evolutionarily conserved serine/threonine kinase of the phosphoinositide 3-kinase (PI3K) related kinase family, the mechanistic/mammalian target of rapamycin (mTOR) plays vital roles in the PI3K/AKT/mTOR pathway, participating in different cellular processes including cell survival, metabolism and proliferation. Aberrant activity of this signaling pathway may lead to oncogenesis. Over the last two decades, great progress has been made in the understanding of mTOR activation and how its response is counteracted for maintaining tissue homeostasis. Besides regulatory proteins and microRNAs, long noncoding RNA (lncRNA) is another emerging critical layer of the intricate modulatory architecture for the control of the mTOR signaling circuit. Also, the production of numerous lncRNAs is induced by mTOR treatment. These findings offer new perspectives for designing novel diagnostic and therapeutic strategies. In this review, we summarize the interactions between the mTOR signaling pathway and lncRNAs in the development and progression of various types of tumors, focusing on the mechanisms of these interactions, and also discuss the potential use of lncRNAs as biomarkers and therapeutic targets for malignancies.

摘要

作为磷酸肌醇 3-激酶(PI3K)相关激酶家族中进化保守的丝氨酸/苏氨酸激酶,机械/哺乳动物靶标雷帕霉素(mTOR)在 PI3K/AKT/mTOR 通路中发挥着重要作用,参与包括细胞存活、代谢和增殖在内的不同细胞过程。该信号通路的异常活性可能导致肿瘤发生。在过去的二十年中,人们在理解 mTOR 的激活及其如何通过拮抗反应来维持组织内稳态方面取得了重大进展。除了调节蛋白和 microRNA 外,长链非编码 RNA(lncRNA)也是调控 mTOR 信号通路的复杂调节结构中的另一个新兴关键层。此外,mTOR 处理会诱导产生大量的 lncRNA。这些发现为设计新的诊断和治疗策略提供了新的视角。在本文综述中,我们总结了 mTOR 信号通路与 lncRNA 在各种类型肿瘤的发生和发展中的相互作用,重点讨论了这些相互作用的机制,并探讨了 lncRNA 作为恶性肿瘤的生物标志物和治疗靶点的潜在用途。

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