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Microcystin-LR-induced autophagy via miR-282-5p/PIK3R1 pathway in Eriocheir sinensis hepatopancreas

文献类型： 外文期刊

作者： Zhang, Yuning 1 ; Gao, Jiancao 1 ; Cao, Liping 2 ; Du, Jinliang 2 ; Xu, Gangchun 1 ; Xu, Pao 1 ;

作者机构： 1.Nanjing Agr Univ, Wuxi Fisheries Coll, Wuxi 214081, Peoples R China

2.Chinese Acad Fishery Sci, Freshwater Fisheries Res Ctr, Key Lab Integrated Rice Fish Farming Ecol, Minist Agr & Rural Affairs, Wuxi 214081, Peoples R China

关键词： Microcystin-LR; Eriocheir sinensis; MiRNA; MiR-282-5p; Autophagy

期刊名称：ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY （ 影响因子：6.8； 五年影响因子：6.9 ）

ISSN： 0147-6513

年卷期： 2023 年 267 卷

页码：

收录情况： SCI

摘要： With the intensifying climate warming, blue-green algae blooms have become more frequent and severe, releasing environmental hazards such as microcystin that pose potential threats to human and animal health. Autophagy has been shown to play a crucial role in regulating immune responses induced by environmental hazards, enabling cells to adapt to stress and protect against damage. Although microcystin-LR (MC-LR) has been identified to affect autophagy in mammalian, its impact on aquatic animals has been poorly studied. To inves-tigate the toxicological effects of MC-LR in aquatic ecosystems, we constructed a microRNA profile of acute MC-LR stress in the hepatopancreas of the Chinese mitten crab. Interestingly, we found the MC-LR exposure activated autophagy in the hepatopancreas based on the following evidence. Specifically, mRNA expression level of ATG7, Beclin1 and Gabarap was significantly up-regulated, autophagy regulatory pathways were significantly enriched, and numerous autolysosomes and autophagosomes were observed. Additionally, we found that miR-282-5p and its target gene PIK3R1 played important regulatory roles in autophagy by in vivo and in vitro experiments. Overexpression of miR-282-5p mimicked MC-LR-induced autophagy by inhibiting PIK3R1 expression, while miR-282-5p silencing inhibited autophagy by promoting PIK3R1 expression. Altogether, our findings suggest that MC-LR increases miR-282-5p, which then targets inhibition of PIK3R1 to stimulate autophagy. This study focused on the stress response regulatory mechanisms of juvenile crabs to toxic pollutants in water, offering a potential target for alleviating the toxicity of MC-LR. These findings lay a foundation for reducing the toxicity of MC-LR and environmental hazards in organisms.

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