Long noncoding RNA TUG1 contributes to cerebral ischaemia/reperfusion injury by sponging mir-145 to up-regulate AQP4 expression.

Weifeng Shan,Yueying Zheng,Manli Chen,Wei Chen,Xian Zhao,Shengmei Zhu,Yang Yu,Aijie Pei

doi:10.1111/jcmm.14712

Abstract

Emerging studies have shown that long noncoding RNA (lncRNA) TUG1 (taurine‐up‐regulated gene 1) plays critical roles in multiple biological processes. However, the expression and function of lncRNA TUG1 in cerebral ischaemia/reperfusion injury have not been reported yet. In this study, we found that LncRNA TUG1 expression was significantly up‐regulated in cultured MA‐C cells exposed to OGD/R injury, while similar results were also observed in MCAO model. Mechanistically, knockdown of TUG1 decreased lactate dehydrogenase levels and the ratio of apoptotic cells and promoted cell survival in vitro. Moreover, knockdown of TUG1 decreased AQP4 (encoding aquaporin 4) expression to attenuate OGD/R injury. TUG1 could interact directly with miR‐145, and down‐regulation of miR‐145 could efficiently reverse the function of TUG1 siRNA on AQP4 expression. Finally, the TUG1 shRNA reduced the infarction area and cell apoptosis in I/R mouse brains in vivo. In summary, our results suggested that lncRNA TUG1 may function as a competing endogenous RNA (ceRNA) for miR‐145 to induce cell damage, possibly providing a new therapeutic target in cerebral ischaemia/reperfusion injury.

Highlights

Ischaemia/reperfusion (I/R) is considered important for the recov‐ ery of ischaemic brain injury and limits subsequent infarction development.[1]
We employed a middle cerebral artery occlu‐ sion (MCAO) model and MA‐C cell oxygen‐glucose deprivation and reperfusion (OGD/R) model to determine whether Taurine‐up‐ regulated gene 1 (TUG1) expression was altered in cerebral ischaemia/reperfusion injury (IRI)
We found that TUG1 was significantly up‐regulated after OGD/R treatment and in the MCAO model

Summary

| INTRODUCTION

Ischaemia/reperfusion (I/R) is considered important for the recov‐ ery of ischaemic brain injury and limits subsequent infarction development.[1]. It has been reported that TUG1 was up‐regulated in the brain of middle cerebral artery occlu‐ sion (MCAO) and oxygen‐glucose deprivation (OGD)‐treated SH‐SY5Y cells, indicating the therapeutic potential of TUG1 in I/R.12. We employed a MCAO model and MA‐C cell oxygen‐glucose deprivation and reperfusion (OGD/R) model to determine whether TUG1 expression was altered in cerebral IRI. Our study provides new insights into the molecular func‐ tion of the TUG1/miR‐145/AQP4 signalling pathway in the patho‐ genesis of cerebral IRI and highlights the potential of lncRNAs to act as new therapeutic targets in cerebral IRI

| MATERIALS AND METHODS

| DISCUSSION

| CONCLUSION

Findings

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