c-MYC-induced long noncoding RNA MEG3 aggravates kidney ischemia–reperfusion injury through activating mitophagy by upregulation of RTKN to trigger the Wnt/β-catenin pathway

Autor: Xiaotong Zheng, Dajun Liu, Ying Liu, Naiquan Liu
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Male
0301 basic medicine
Cancer Research
Apoptosis
urologic and male genital diseases
Kidney Tubules
Proximal
0302 clinical medicine
Mitophagy
Wnt Signaling Pathway
MEG3
Chemistry
lcsh:Cytology
Wnt signaling pathway
Acute Kidney Injury
female genital diseases and pregnancy complications
Mitochondria
Up-Regulation
medicine.anatomical_structure
Reperfusion Injury
030220 oncology & carcinogenesis
Female
RNA
Long Noncoding
Renal cortex
Immunology
Article
Cell Line
Proto-Oncogene Proteins c-myc
03 medical and health sciences
Cellular and Molecular Neuroscience
Downregulation and upregulation
GTP-Binding Proteins
medicine
Animals
Humans
cardiovascular diseases
lcsh:QH573-671
Renal ischemia
urogenital system
fungi
Cell Biology
Mice
Inbred C57BL
Disease Models
Animal
MicroRNAs
030104 developmental biology
Catenin
Long non-coding RNAs
Cancer research
Apoptosis Regulatory Proteins
Zdroj: Cell Death and Disease, Vol 12, Iss 2, Pp 1-16 (2021)
Cell Death & Disease
ISSN: 2041-4889
Popis: Ischemia–reperfusion injury (IRI)-induced acute kidney injury (AKI) is a life-threatening disease. The activation of mitophagy was previously identified to play an important role in IRI. Maternally expressed 3 (MEG3) can promote cerebral IRI and hepatic IRI. The present study was designed to study the role of MEG3 in renal IRI. Renal IRI mice models were established, and HK-2 cells were used to construct the in vitro models of IRI. Hematoxylin–eosin staining assay was applied to reveal IRI-triggered tubular injury. MitoTracker Green FM staining and an ALP kit were employed for detection of mitophagy. TdT-mediated dUTP-biotin nick-end labeling assay was used to reveal cell apoptosis. The results showed that renal cortex of IRI mice contained higher expression of MEG3 than that of sham mice. MEG3 expression was also elevated in HK-2 cells following IRI, suggesting that MEG3 might participate in the development of IRI. Moreover, downregulation of MEG3 inhibited the apoptosis of HK-2 cells after IRI. Mitophagy was activated by IRI, and the inhibition of MEG3 can restore mitophagy activity in IRI-treated HK-2 cells. Mechanistically, we found that MEG3 can bind with miR-145-5p in IRI-treated cells. In addition, rhotekin (RTKN) was verified to serve as a target of miR-145-5p. MEG3 upregulated RTKN expression by binding with miR-145-5p. Further, MEG3 activated the Wnt/β-catenin pathway by upregulation of RTKN. The downstream effector of Wnt/β-catenin pathway, c-MYC, served as the transcription factor to activate MEG3. In conclusion, the positive feedback loop of MEG3/miR-145-5p/RTKN/Wnt/β-catenin/c-MYC promotes renal IRI by activating mitophagy and inducing apoptosis, which might offer a new insight into the therapeutic methods for renal IRI in the future.
Databáze: OpenAIRE
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