Knockdown of lncRNA TTTY15 alleviates ischemia/reperfusion‑induced inflammation and apoptosis of PC12 cells by targeting miR‑766‑5p

Abstract

The pathogenesis of ischemic stroke is extremely complex and has a significant impact on the quality of life of the patients. Accumulating studies have reported that long non-coding RNAs (lncRNAs) may be associated with the progression of ischemic stroke. However, the role and underlying mechanism of action of the lncRNA testis-specific transcript Y-linked 15 (TTTY15) in ischemic stroke remains unknown. The present study analyzed the expression levels of TTTY15 in PC12 cells injured by oxygen-glucose deprivation/reperfusion (OGD/R). The effects of the knockdown of TTTY15 expression on the levels of the inflammatory cytokines TNF-α, IL-1β, IL-18 and IL-10, cell apoptosis and the expression levels of the apoptosis-associated proteins Bcl-2, Bax, cleaved caspase-3, caspase-3, cleaved caspase-9 and caspase-9, were subsequently analyzed in OGD/R-treated PC12 cells using ELISA, flow cytometry and western blotting, respectively. In addition, the downstream target gene of TTTY15 was verified using a dual luciferase reporter assay. The effects of TTTY15 on the inflammation and apoptosis of PC12 cells treated with OGD/R were determined by targeting miR-766-5p. The results of the present study revealed that TTTY15 expression was upregulated in OGD/R-treated PC12 cells. The knockdown of TTTY15 significantly decreased the concentrations of the proinflammatory factors TNF-α, IL-1β and IL-18, while it increased the concentration of the anti-inflammatory cytokine IL-10 in OGD/R-treated PC12 cells. Apoptosis was also suppressed following gene silencing of TTTY15. Subsequently, miR-766-5p was identified as a target gene of TTTY15 using a dual luciferase reporter assay and the expression levels of TTTY15 and miR-766-5p were found to be negatively correlated. The overexpression of miR-766-5p alleviated the stimulatory effect of TTTY15 overexpression on the inflammation and apoptosis of PC12 cells treated with OGD/R. Therefore, the present study revealed that TTTY15 knockdown improved the OGD/R-induced injury of PC12 cells by upregulating miR-766-5p expression.

Circular RNA protein tyrosine kinase 2 aggravates pyroptosis and inflammation in septic lung tissue by promoting microRNA-766/eukaryotic initiation factor 5A axis-mediated ATP efflux

“…This study identified a potential downstream miRNA (miR-766) of circPTK2 and found that miR-766 was down-expressed in both models of septic ALI, but circPTK2 depletion restored miR-766 levels. miR-766 has been recognized to suppress skin inflammation 35 and attenuate ischemia/perfusion injury-induced cellular inflammation and apoptosis 36 . The paper demonstrated that miR-766 overexpression mitigated the effects of circPTK2 overexpression on cytotoxicity, eATP levels, inflammation, and pyroptosis.…”

Long non-coding RNA TTTY15 silencing inhibits gastric cancer progression by sponging microRNA-98-5p to down-regulate cyclin D2 expression

“…As a newly discovered lncRNA, TTTY15 has been shown to play a crucial role in cardiovascular diseases. For instance, Zheng et al [ 34 ], Chen et al [ 35 ], Huang et al [ 36 ], Hao et al [ 37 ], and Zhang et al [ 38 ] have reported that TTTY15 silencing can sponge miR-186-5p, miR-374a-5p, miR-455-5p, miR-766-5p, and let-7i-5p to mitigate hypoxia-induced vascular endothelial cell injury. Moreover, dysregulation of TTTY15 has been observed in various cancers.…”

On The Origin of Speciation

“…As mentioned above, according to Orr's observation (Orr, 1993), the testis-specific expression of Xt-mir seems to be controlled by the gene on the Y chromosome. Although there is no miRNA on the Y chromosome (Ji et al, 2016), Long noncoding RNA (lncRNA) was present, and it was shown that KO of Y-linked lncRNA upregulated miRNA and suppressed apoptosis (Hao et al, 2021). LncRNA, which is non-coding RNA with a length of 200 bases or more, exists widely in diverse species including viruses, prokaryotes, and eukaryotes, and is often expressed organ-specifically in animals, especially in the testis (Hong et al, 2018).…”