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Silencing lncRNA KCNQ1OT1 reduced hepatic ischemia reperfusion injury-induced pyroptosis by regulating miR-142a-3p/HMGB1 axis

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Abstract

Background

Based on pre-existing evidence, KCNQ1OT1 has been pointed out to be closely related to myocardial and cerebral ischemia reperfusion injury diseases. Herein, the objective of our study is to probe into the potential function as well as the underlying mechanism of KCNQ1OT1 on hepatic ischemia reperfusion injury (HIRI).

Methods

Using C57BL/6 J mice and primary mouse hepatocytes were conducted to establish HIRI model in vivo and in vitro. Cell viability was examined using CCK-8 assay and EdU assay. Flow cytometric analysis was performed to evaluate the pyroptosis. Dual-luciferase reporter assay was employed to verify the interaction relationships. qRT-PCR and Western blot were adopted to analyze the mRNA and protein level. Histopathological alteration of liver tissue was evaluated by HE staining. Immunohistochemistry (IHC) was performed to measure NLRP3 and caspase 1.

Results

Our data revealed that KCNQ1OT1 expression was ascending in hepatic tissue of HIRI mouse. Moreover, deprivation of KCNQ1OT1 mitigated I/R-induced hepatic injury and pyroptosis in vivo. Further experiments demonstrated that silencing KCNQ1OT1 promoted proliferation and inhibited pyroptosis in hypoxia/reoxygenation (H/R)-induced primary mouse hepatocytes. Mechanistically, KCNQ1OT1 functioned as a competing endogenous RNA which sponged miR-142a-3p, therefore promoted HMGB1 expression to activate TLR4/NF-κB signaling pathway in HIRI.

Conclusion

LncRNA KCNQ1OT1 elevated HMGB1 expression through binding to miR-142a-3p, thereby promoting pyroptosis in HIRI.

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Availability of data and material

The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.

Code availability

Not applicable.

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Acknowledgements

Not applicable.

Funding

This study was supported by Hunan Cancer Hospital Climb Plan (Grant No. 2020NSFC-A002), Hunan Provincial Natural Science Foundation of China (Grant No. 2019JJ80020), and Hunan Provincial Natural Science Foundation of China (Grant No. 806268174046).

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Authors and Affiliations

  1. Department of Anesthesiology, Hunan Cancer Hospital, Hunan Province, No. 283 Tongzipo Road, Changsha, 410013, China

    Canxin Liang, Yanhua Peng, Huiping Sun, Lijuan Wang, Liubing Jiang & Shuangfa Zou

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  1. Canxin Liang
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  2. Yanhua Peng
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  3. Huiping Sun
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Contributions

CL contributed to conceptualization, methodology, and writing- Original draft preparation; YP contributed to data curation; HS and LW contributed to visualization and investigation; LJ contributed to validation; and SZ contributed to supervision, writing- reviewing, and editing.

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Correspondence to Shuangfa Zou.

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All animal experiments and related procedures were approved by the Ethics Committee of Hunan Cancer Hospital (approval No. 2021–074).

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Liang, C., Peng, Y., Sun, H. et al. Silencing lncRNA KCNQ1OT1 reduced hepatic ischemia reperfusion injury-induced pyroptosis by regulating miR-142a-3p/HMGB1 axis. Mol Cell Biochem 478, 1293–1305 (2023). https://doi.org/10.1007/s11010-022-04586-y

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