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Background <p>Acute lung injury (ALI) secondary to sepsis increases the risk of mortality in septic patients. However, the molecular mechanism of alveolar epithelial cell damage in ALI secondary to sepsis remains incompletely understood. Studies demonstrate that circular RNA (circRNA) modulates the progression of ALI secondary to sepsis. This study aims to explore the function and mechanisms of circ-PRKCI in ALI associated with sepsis.</p> Methods <p>The in vitro ALI model was constructed by treating MLE-12 cells with LPS. The expression of circ-PRKCI, miR-106b-5p, GRB2-associated binder 1 (GAB1), and inflammatory cytokines was measured via RT-qPCR. The expression of apoptosis-related proteins and GAB1 protein was analyzed via Western blot. The subcellular localization of circ-PRKCI was determined using immunofluorescence. Cell viability was measured by the CCK-8 assay, and apoptosis was evaluated using flow cytometry. ELISA was employed to measure pro-inflammatory cytokine concentrations in cells and lung tissue samples. The content of oxidative stress markers was measured utilizing corresponding assay kits. The binding relationship between miR-106b-5p and circ-PRKCI or GAB1 was validated through dual-luciferase reporter assays and RNA RIP experiments. The in vivo ALI model was constructed via cecal ligation and puncture (CLP) surgery. HE staining and the W/D ratio test were performed on mouse lung tissues to evaluate the extent of lung injury.</p> Results <p>The findings revealed that circ-PRKCI attenuated apoptosis, inflammation, and oxidative stress in ALI-induced cells, while also suppressing pulmonary inflammation, edema, and apoptotic responses in the murine ALI model. However, miR-106b-5p was capable of reversing the function of circ-PRKCI. Mechanistically, circ-PRKCI modulated the expression of GAB1 by competitively binding to miR-106b-5p.</p> Conclusion <p>Our findings indicated that circ-PRKCI attenuates ALI secondary to sepsis by targeting the miR-106b-5p/GAB1 axis, suggesting that circ-PRKCI holds potential as a therapeutic target for ALI secondary to sepsis.</p>

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Circ-PRKCI attenuates acute lung injury secondary to sepsis by targeting the miR-106b-5p/GAB1 axis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月13日

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  • Yingjie Yin,
  • Shouqing Zhang,
  • Jiebing Zheng,
  • Xinnian Wang,
  • Qin Huang,
  • Biqing Yan

摘要

Background

Acute lung injury (ALI) secondary to sepsis increases the risk of mortality in septic patients. However, the molecular mechanism of alveolar epithelial cell damage in ALI secondary to sepsis remains incompletely understood. Studies demonstrate that circular RNA (circRNA) modulates the progression of ALI secondary to sepsis. This study aims to explore the function and mechanisms of circ-PRKCI in ALI associated with sepsis.

Methods

The in vitro ALI model was constructed by treating MLE-12 cells with LPS. The expression of circ-PRKCI, miR-106b-5p, GRB2-associated binder 1 (GAB1), and inflammatory cytokines was measured via RT-qPCR. The expression of apoptosis-related proteins and GAB1 protein was analyzed via Western blot. The subcellular localization of circ-PRKCI was determined using immunofluorescence. Cell viability was measured by the CCK-8 assay, and apoptosis was evaluated using flow cytometry. ELISA was employed to measure pro-inflammatory cytokine concentrations in cells and lung tissue samples. The content of oxidative stress markers was measured utilizing corresponding assay kits. The binding relationship between miR-106b-5p and circ-PRKCI or GAB1 was validated through dual-luciferase reporter assays and RNA RIP experiments. The in vivo ALI model was constructed via cecal ligation and puncture (CLP) surgery. HE staining and the W/D ratio test were performed on mouse lung tissues to evaluate the extent of lung injury.

Results

The findings revealed that circ-PRKCI attenuated apoptosis, inflammation, and oxidative stress in ALI-induced cells, while also suppressing pulmonary inflammation, edema, and apoptotic responses in the murine ALI model. However, miR-106b-5p was capable of reversing the function of circ-PRKCI. Mechanistically, circ-PRKCI modulated the expression of GAB1 by competitively binding to miR-106b-5p.

Conclusion

Our findings indicated that circ-PRKCI attenuates ALI secondary to sepsis by targeting the miR-106b-5p/GAB1 axis, suggesting that circ-PRKCI holds potential as a therapeutic target for ALI secondary to sepsis.