Journal
JOURNAL OF CELLULAR BIOCHEMISTRY
Volume 121, Issue 11, Pages 4522-4534Publisher
WILEY
DOI: 10.1002/jcb.29669
Keywords
acute kidney injury; autophagy; EGOT; HK-2; HuR; lncRNA
Categories
Funding
- Ministry of Science and Technology, Taiwan [MOST 106-2314-B-039-013-MY3, MOST 1062314-B-039-032, MOST 107-2811-B-039507, MOST 108-2811-B-039-508]
- China Medical University Hospital [DMR-106-088]
Ask authors/readers for more resources
Autophagy, an important cellular homeostatic mechanism regulates cell survival under stress and protects against acute kidney injury. However, the role of long noncoding RNA (lncRNA) in autophagy regulation in renal tubular cells (HK-2) is unclear. The study was aimed to understand the importance of lncRNA in hypoxia-induced autophagy in HK-2 cells. LncRNA eosinophil granule ontogeny transcript (EGOT) was identified as autophagy-associated lncRNA under hypoxia. The lncRNA EGOT expression was significantly downregulated in renal tubular cells during hypoxia-induced autophagy. Gain- and loss-of-EGOT functional studies revealed that EGOT overexpression reduced autophagy by downregulation of ATG7, ATG16L1, LC3II expressions and LC 3 puncta while EGOT knockdown reversed the suppression of autophagy. Importantly, RNA-binding protein, (ELAVL1)/Hu antigen R (HuR) binds and stabilizes the EGOT expression under normoxia and ATG7/16L1 expressions under hypoxia. Furthermore, HuR mediated stabilization of ATG7/16L1 expressions under hypoxia causes a decline in EGOT levels and thereby promotes autophagy. Altogether, the study first reveals the functional interplay of lncRNA EGOT and HuR on the posttranscriptional regulation of the ATG7/16L1 expressions. Thus, the HuR/EGOT/ATG7/16L1 axis is crucial for hypoxia-induced autophagy in renal tubular cells.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available