Targeting the lncMST-EPRS/HSP90AB1 complex as novel therapeutic strategy for T-2 toxin-induced growth retardation
Targeting the lncMST-EPRS/HSP90AB1 complex as novel therapeutic strategy for T-2 toxin-induced growth retardation
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DOI：
10.1016/j.ecoenv.2022.114243
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发表时间：
2022-11-01
影响因子：
6.8
通讯作者：
Wang，Xu
中科院分区：
文献类型：
--
作者：
Lu，Qirong;Guo，Pu;Wang，Xu
生长迟缓是一个全球性的公共卫生问题，特别是在低收入和中等收入国家非常普遍，这与食用受T-2毒素污染的谷物密切相关，对人类和动物健康构成风险。然而，可能的目标，可以减轻T-2毒素诱导的生长迟缓仍需要探索。本研究以T-2毒素作为环境暴露因子诱导生长迟缓，并进一步探讨lncRNA在生长迟缓中的调控作用。本研究系统地表征了lncRNA的表达谱，并鉴定了与T-2毒素给药大鼠生长迟缓相关的lncRNA lncMST。在功能上，lncMST可以减轻T-2毒素处理的GH 3细胞的细胞周期阻滞和凋亡。在机制上，lncMST作为诱导型伴侣RNA，通过募集EPRS/HSP 90 AB 1复合物来增加HDAC 6表达，从而进一步减轻T-2毒素诱导的生长迟缓，参与“化学诱导的应激相关的生长迟缓”范例。这些发现首次证实了lncMST与生长迟缓之间可能的治疗关系，为生长迟缓的发病机制提供了解释和治疗靶点。
Growth retardation is a global public health problem that is highly prevalent especially in low-and middle-income countries, which is closely related to the consumption of grains contaminated with T-2 toxin, a risk for human and animal health. However, the possible targets that can relieve T-2 toxin-induced growth retardation still need to be explored. In the present study, T-2 toxin was used as an environmental exposure factor to induce growth retardation and further explore the regulatory role of lncRNA in growth retardation. The present study systematically characterised the expression profiles of lncRNAs and identified a lncRNA lncMST that is related to growth retardation in T-2 toxin-administered rats. Functionally, lncMST could alleviate cell cycle arrest and apoptosis in T-2 toxin-treated GH3 cells. Mechanistically, lncMST, serve as an inducible chaperone RNA, involved in the paradigm “Chemical-induced stress related growth retardation”, through recruiting the EPRS/HSP90AB1 complex to increase HDAC6 expression, thus further alleviating T-2 toxin-induced growth retardation. These findings for the first time demonstrate that the probable therapeutic relationship between lncMST and growth retardation, providing an explanation and therapeutic targets for the pathogenesis of growth retardation.