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Retracted: Protection of miR-19b in hypoxia/reoxygenation-induced injury by targeting PTEN
Wan-Gen Liu1, Li-Li Han1, Rong Xiang1
1Department of Neurology, Cangzhou Central Hospital, Cangzhou, Hebei, China.
Objective:
To study the role and mechanism of microRNA 19b (miR-19b) in hypoxia/reoxygenation (H/R)-induced injury by targeting PTEN.
Methods:
PC12 and BV2 cells induced by H/R were treated with miR-19b mimics/inhibitors or small interfering PTEN (si-PTEN), respectively. Lactate dehydrogenase (LDH) level, malondialdehyde (MDA), and superoxide dismutase (SOD) content was detected. Besides, cell viability and apoptosis were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, Hoechst33342 staining, and flow cytometry, whereas mitochondrial membrane potential (MMP) tested by JC-1 assay, and reactive oxygen species (ROS) evaluated by the dichloro-dihydro-fluorescein diacetate assay. The ischemia/reperfusion (I/R) rats model was used to investigate the effects of miR-19b in vivo test. The infarct area and apoptosis rates in brain tissues were detected by 2,3,5-triphenyltetrazolium chloride and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining, respectively. miR-19b and PTEN/PI3K/Akt pathway-related proteins were detected by quantitative reverse-transcription polymerase chain reaction and western blot analysis.
Results:
miR-19b mimics could reduce LDH, MDA, and ROS levels and decline cell apoptosis, but enhance the viability, MMP, and SOD activity with decreased PTEN and cleaved caspase, as well as increased p-Akt/Akt and Bcl-2/Bax ratios in H/R-induced PC12 and BV2 cells. However, miR-19b inhibitors led to completely opposite results to aggravate H/R-induced cell injury. Meanwhile, si-PTEN could reverse the effect of miR-19b inhibitors on H/R-induced injury. Moreover, treatment with miR-19b agomir after I/R in vivo sufficiently decreased infarct area and reduced apoptosis rates by targeting PTEN through the regulation of the PI3K/Akt pathway.
Conclusion:
miR-19b could inhibit oxidative stress, enhance cell MMP, promote cell survival, and inhibit cell apoptosis by targeting PTEN via the regulation of the PI3K/Akt pathway, thus playing the neuronal protective effects.
Insights
MicroRNA 19b (miR-19b) protects neurons from hypoxia/reoxygenation injury by targeting PTEN. This microRNA inhibits oxidative stress and apoptosis, promoting cell survival via the PI3K/Akt pathway.
Area of Science:
- Neuroscience
- Molecular Biology
- Biochemistry
Background:
- Hypoxia/reoxygenation (H/R) induces significant neuronal injury.
- MicroRNAs play crucial roles in regulating cellular processes, including injury responses.
- PTEN is a known regulator of cell survival and apoptosis pathways.
Purpose of the Study:
- To elucidate the role of microRNA 19b (miR-19b) in H/R-induced neuronal injury.
- To investigate the underlying mechanism involving PTEN and the PI3K/Akt pathway.
- To evaluate the therapeutic potential of miR-19b in an in vivo model of ischemia/reperfusion (I/R).
Main Methods:
- Cell viability, apoptosis, oxidative stress markers (LDH, MDA, ROS), and mitochondrial membrane potential (MMP) were assessed in H/R-treated PC12 and BV2 cells.
- In vivo studies utilized an I/R rat model to evaluate infarct area and apoptosis.
- Quantitative reverse-transcription polymerase chain reaction and western blot analysis were employed to detect miR-19b, PTEN, and PI3K/Akt pathway-related proteins.
Main Results:
- miR-19b mimics reduced H/R-induced cell injury by decreasing oxidative stress and apoptosis, while enhancing cell viability and MMP.
- miR-19b inhibition exacerbated H/R injury, and small interfering PTEN (si-PTEN) reversed these effects.
- In vivo, miR-19b treatment significantly reduced infarct size and apoptosis in I/R rats by targeting PTEN and modulating the PI3K/Akt pathway.
Conclusions:
- miR-19b exerts significant neuroprotective effects against H/R injury.
- The mechanism involves inhibiting oxidative stress, preserving mitochondrial function, promoting cell survival, and reducing apoptosis.
- Targeting PTEN and regulating the PI3K/Akt pathway are key to miR-19b's protective action.
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