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lncRNA NEAT1 aggravates sepsis-induced lung injury by regulating the miR-27a/PTEN axis


Sepsis is an acute inflammatory reaction and a cause of acute respiratory distress syndrome (ARDS). In the present study, we explored the roles and underlying mechanism of the lncRNA Nuclear enriched abundant transcript 1 (NEAT1) in ARDS. The expression levels of genes, proteins and pro-inflammatory cytokines in patients with ARDS, LPS-stimulated cells and septic mouse models were quantified using qPCR, western blotting and ELISA assays, respectively. The molecular targeting relationship was validated by conducting a dual-luciferase reporter assay. Cell proliferation was assessed using the Cell Counting Kit-8 (CCK-8) assay. The cell cycle phase was determined by flow cytometry assay. The expression levels of NEAT1 and pro-inflammatory cytokines were higher in patients with ARDS and septic models than in controls. Knockdown of NEAT1 significantly increased cell proliferation and cycle progression and prolonged mouse survival in vitro and in vivo. Mechanistically, miR-27a was identified as a downstream target of NEAT1 and directly inhibited PTEN expression. Further rescue experiments revealed that inhibition of miR-27a impeded the promoting effects of NEAT1 silence on cell proliferation and cycle progression, whereas inhibition of PTEN markedly weakened the inhibitory effects of NEAT1 overexpression on cell proliferation and cycle progression. Altogether, our study revealed that NEAT1 plays a promoting role in the progression of ARDS via the NEAT1/miR-27a/PTEN regulatory network, providing new insight into the pathologic mechanism behind ARDS.

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Fig. 1: The expression levels of NEAT1 and inflammatory cytokines in ARDS patients and LPS-induced cells.
Fig. 2: Knockdown of NEAT1 attenuated LPS-induced lung cell injury.
Fig. 3: miR-27a was a downstream target of NEAT1.
Fig. 4: miR-27a reversed the effects of NEAT1 on the cell cycle and inflammatory response.
Fig. 5: PTEN functioned as an effector of miR-27a.
Fig. 6: PTEN participated in the regulatory effect of NEAT1 on LPS-induced cell injury.
Fig. 7: The role of NEAT1 knockdown in CLP-induced lung injury in mice.
Fig. 8

Data availability

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


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This work is supported by special funds for basic scientific research business expenses of the central public welfare research institutes of the Chinese Academy of Medical Sciences (No. 2019PT32000), Doctor Foundation of Guizhou Provincial People’s Hospital (GZSYBS [2019]04).

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XL: study concepts, definition of intellectual content and statistical analysis; XYZ: study concepts, manuscript preparation and editing; YJN: data acquisition and definition of intellectual content; GHL and QZ: literature research and experimental studies; XF: data analysis and statistical analysis; SY: data analysis; QHZ: study design, manuscript preparation and editing and manuscript review; JQL: guarantor of integrity of the entire study, study concepts and design and manuscript review. All authors read and approved the final manuscript.

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Correspondence to Qing-Hua Zhao or Jian-Quan Li.

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All protocol was approved by the Ethics Committee of Guizhou Provincial People’s Hospital and conducted according to the Declaration of Helsinki.

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Lv, X., Zhang, XY., Zhang, Q. et al. lncRNA NEAT1 aggravates sepsis-induced lung injury by regulating the miR-27a/PTEN axis. Lab Invest 101, 1371–1381 (2021).

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