Int J Biol Sci 2021; 17(14):3968-3980. doi:10.7150/ijbs.58910 This issue Cite

Research Paper

Long non-coding RNA MEG3 promotes cisplatin-induced nephrotoxicity through regulating AKT/TSC/mTOR-mediated autophagy

Xu Jing1, Jinming Han2, Junhao Zhang3, Yi Chen4, Juan Yuan5, Jue Wang6, Shiyong Neo4, Shuijie Li7, Xueyuan Yu8, Jing Wu9✉

1. Department of Clinical Laboratory, The Second Hospital of Shandong University, Jinan, 250000, China.
2. Department of Clinical Neuroscience, Karolinska Institutet, S-171 76, Sweden.
3. Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
4. Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
5. Department of Cell and Molecular Biology, Karolinska Institutet, S-171 76, Sweden.
6. Key Laboratory, The Second Hospital of Shandong University, Jinan, 250000, China.
7. Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, S-171 76, Sweden.
8. Department of Nephrology, Qilu hospital of Shandong University, Jinan, China.
9. Department of Pharmacology, The Second Hospital of Shandong University, Jinan, 250000, China.

Citation:
Jing X, Han J, Zhang J, Chen Y, Yuan J, Wang J, Neo S, Li S, Yu X, Wu J. Long non-coding RNA MEG3 promotes cisplatin-induced nephrotoxicity through regulating AKT/TSC/mTOR-mediated autophagy. Int J Biol Sci 2021; 17(14):3968-3980. doi:10.7150/ijbs.58910. https://www.ijbs.com/v17p3968.htm
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Abstract

Graphic abstract

Cis-Diamminedichloroplatinum (II) (DDP)-induced nephrotoxicity (DDPIN) may cause irreversible renal injury associated with high morbidity and mortality. Current standard therapies have not achieved satisfactory clinical outcomes due to unclear molecular and cellular mechanisms. Therefore, exploring potential therapies on DDPIN represents an urgent medical need. Present study characterized the role of lncRNA maternally expressed gene 3 (lnc-MEG3) in the pathogenesis of DDPIN. In both in vitro and in murine models of DDP-induced nephrotoxicity, lnc-MEG3 exacerbated DDPIN by negatively regulating miRNA-126 subsequently causing a decreased AKT/TSC/mTOR-mediated autophagy. By silencing lnc-MEG3 or incorporating miRNA-126 mimetics, the proliferation and migration of DDP-treated cells were restored. In vivo, we identified Paeonol to alleviate DDPIN by the inhibition of lnc-MEG3. Taken together, lnc-MEG3 represents a novel therapeutic target for DDPIN and Paeonol may serve as a promising treatment by inhibiting lnc-MEG3 and its related signaling pathways.

Keywords: lncRNA MEG3, DDPIN, miRNA-126, autophagy


Citation styles

APA
Jing, X., Han, J., Zhang, J., Chen, Y., Yuan, J., Wang, J., Neo, S., Li, S., Yu, X., Wu, J. (2021). Long non-coding RNA MEG3 promotes cisplatin-induced nephrotoxicity through regulating AKT/TSC/mTOR-mediated autophagy. International Journal of Biological Sciences, 17(14), 3968-3980. https://doi.org/10.7150/ijbs.58910.

ACS
Jing, X.; Han, J.; Zhang, J.; Chen, Y.; Yuan, J.; Wang, J.; Neo, S.; Li, S.; Yu, X.; Wu, J. Long non-coding RNA MEG3 promotes cisplatin-induced nephrotoxicity through regulating AKT/TSC/mTOR-mediated autophagy. Int. J. Biol. Sci. 2021, 17 (14), 3968-3980. DOI: 10.7150/ijbs.58910.

NLM
Jing X, Han J, Zhang J, Chen Y, Yuan J, Wang J, Neo S, Li S, Yu X, Wu J. Long non-coding RNA MEG3 promotes cisplatin-induced nephrotoxicity through regulating AKT/TSC/mTOR-mediated autophagy. Int J Biol Sci 2021; 17(14):3968-3980. doi:10.7150/ijbs.58910. https://www.ijbs.com/v17p3968.htm

CSE
Jing X, Han J, Zhang J, Chen Y, Yuan J, Wang J, Neo S, Li S, Yu X, Wu J. 2021. Long non-coding RNA MEG3 promotes cisplatin-induced nephrotoxicity through regulating AKT/TSC/mTOR-mediated autophagy. Int J Biol Sci. 17(14):3968-3980.

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