The transcription factor Foxd3 induces spinal cord ischemia-reperfusion injury by potentiating microRNA-214-dependent inhibition of Kcnk2

Li, Ran; Zhao, Kunchi; Ruan, Qing; Meng, Chunyang; Yin, Fei

doi:10.1038/s12276-019-0370-8

Cited by 13 publications

(7 citation statements)

References 40 publications

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“…Cumulative evidences illustrate that miRs are novel molecular targets modulating the pathogenesis of I/R injury ( Li et al, 2015 , 2017 ; Liu et al, 2017 ; Li et al, 2018 ; Li et al, 2020 ). The associations of miR-128-3p with central nervous system diseases have been assessed previously.…”

Section: Discussionmentioning

confidence: 99%

MiR-128-3p Alleviates Spinal Cord Ischemia/Reperfusion Injury Associated Neuroinflammation and Cellular Apoptosis via SP1 Suppression in Rat

et al. 2020

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BackgroundNeuroinflammation and cellular apoptosis caused by spinal cord ischemia/reperfusion (I/R) injury result in neurological dysfunction. MicroRNAs (miRs) have crucial functions in spinal cord I/R injury pathogenesis according to previous evidences. Herein, whether miR-128-3p contributes to spinal cord I/R injury by regulating specificity protein 1 (SP1) was assessed.MethodsA rat model of spinal cord I/R injury was established by occluding the aortic arch for 14 min. Then, miR-128-3p’s interaction with SP1 was detected by dual-luciferase reporter assays. Next, miR-128-3p mimic and inhibitor, as well as adenovirus-delivered shRNA specific for SP1 were injected intrathecally for assessing the effects of miR-128-3p and SP1 on rats with spinal cord I/R injury. SP1, Bax and Bcl-2 expression levels in I/R injured spinal cord tissues were evaluated by Western blotting, while IL-1β, TNF-α, and IL-6 were quantitated by ELISA. Tarlov scores were obtained to detect hind-limb motor function. Evans blue (EB) dye extravasation was utilized to examine blood–spinal cord barrier (BSCB) permeability. Terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) staining was performed for neuronal apoptosis assessment.ResultsMiR-128-3p expression was decreased, while SP1 amounts were increased in rat spinal cord tissue specimens following I/R. SP1 was identified as a miR-128-3p target and downregulated by miR-128-3p. MiR-128-3p overexpression or SP1 silencing alleviated I/R-induced neuroinflammation and cell apoptosis, and improved Tarlov scores, whereas pretreatment with miR-128-3p inhibitor aggravated the above injuries.ConclusionOverexpression of miR-128-3p protects neurons from neuroinflammation and apoptosis during spinal cord I/R injury partially by downregulating SP1.

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Section: Discussionmentioning

confidence: 99%

MiR-128-3p Alleviates Spinal Cord Ischemia/Reperfusion Injury Associated Neuroinflammation and Cellular Apoptosis via SP1 Suppression in Rat

et al. 2020

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“…FOXD3 was previously unveiled to positively regulate the expression of miRNAs, such as miR-214 and miR-26b [ 7 , 18 ]. This study first demonstrated that FOXD3 upregulated miR-335 by enriching in the promoter region of miR-335.…”

Section: Discussionmentioning

confidence: 99%

FOXD3 confers chemo-sensitivity in ovarian cancer through a miR-335/DAAM1/myosin II axis-dependent mechanism

Wang

Huiuk

et al. 2023

J Ovarian Res

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Background Chemotherapy is among the most common treatment methods for ovarian cancer (OC). However, chemoresistance limits the effectiveness of chemotherapy and leads to treatment failure. We herein investigate the biological effect of forkhead box D3 (FOXD3) in the chemoresistance of OC cells. Methods Expression of FOXD3, miR-335 and disheveled-associated activator of morphogenesis 1 (DAAM1) was detected in OC cells and tissues. The regulatory network of FOXD3/miR-335/DAAM1 was validated by dual-luciferase reporter and ChIP assays in vitro. After ectopic expression and depletion experiments in carboplatin/paclitaxel (CP)-resistant (A2780CP) or sensitive (A2780S) OC cells, cell viability, colony formation and apoptosis were tested by CCK-8 assay, colony formation assay and flow cytometry respectively. Effects of FOXD3 on the chemoresistance of OC cells in vivo were evaluated in OC xenografts in nude mice. Results Overexpression of FOXD3 impaired the proliferation and chemoresistance of OC cells, which was related to the promotion of the miR-335 expression. Functionally, DAAM1 was a putative target of miR-335. Silencing of DAAM1 was responsible for the inhibition of myosin II activation, consequently leading to suppressed OC cell proliferation and chemoresistance. In vivo results further showed that FOXD3 weakened the chemoresistance of OC cells to CP. Conclusion Taken together, we unveil a novel FOXD3/miR-335/DAAM1/myosin II axis that regulates the chemoresistance of OC both in vitro and in vivo.

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“…MiRNAs are important regulators in SCI/R. For example, miR-214 expression was increased in the rat spinal cord tissues and hypoxia/reoxygenation (H/R) H/R-treated PC12 cells, and miR-214 overexpression inhibited cell viability and enhanced cell apoptosis in PC12 cells after exposed to H/R, contributing to the exacerbation of SCI/R injury [ 35 ]. Wang et al found that miR-30c decreased Basso, Beattie and Bresnahan (BBB) score and promoted apoptosis and inflammation by inhibiting SIRT1 expression, thus aggravating SCI/R injury [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Long non-coding RNA H19 contributes to spinal cord ischemia/reperfusion injury through increasing neuronal pyroptosis by miR-181a-5p/HMGB1 axis

Guo

Wang

Alexander

et al. 2022

Aging

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Pyroptosis, a programmed inflammatory necrotizing cell death, is likely involved in spinal cord ischemia-reperfusion (SCI/R) injury, but the mechanisms initiating driving neuronal pyroptosis must be further revealed. The aim of this study is to unravel the mechanism of long non-coding RNA (lncRNA) H19 during SCI/R. SCI/R model was induced in C57BL/6 mice by blocking the aortic arch in vivo , and oxygen-glucose deprivation/reperfusion (OGD/R) injury model of PC12 cells was established in vitro . Our results showed that H19 and HMGB1 expression was upregulated, while miR-181a-5p was downregulated in the SCI/R mice and OGD/R-treated PC12 cells. SCI/R induced pathological damage, pyroptosis and inflammation compared with the sham group. H19 acted as a molecular sponge to suppress miR-181a-5p, and HMGB1 was identified as a direct target of miR-181a-5p. MiR-181a-5p overexpression inhibited the increase of IL-1β, IL-18 and TNF-α production and NLRP3, ASC, and Cleaved-caspase-1 expression in OGD/R-treated PC12 cells; while miR-181a-5p silencing exerted opposite effects. HMGB1 overexpression reversed H19 knockdown-mediated the inhibition of pyroptosis and inflammation in OGD/R-treated PC12 cells. In vivo , H19 knockdown promoted the hind limb motor function recovery and alleviated the pathological damage, pyroptosis and inflammation induced by SCI/R. LncRNA H19/miR-181a-5p/HMGB1 pathway contributes to pyroptosis via activating caspase1 signaling during SCI/R, suggesting that this axis may be a potent therapeutic target in SCI/R.

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The transcription factor Foxd3 induces spinal cord ischemia-reperfusion injury by potentiating microRNA-214-dependent inhibition of Kcnk2

Cited by 13 publications

References 40 publications

MiR-128-3p Alleviates Spinal Cord Ischemia/Reperfusion Injury Associated Neuroinflammation and Cellular Apoptosis via SP1 Suppression in Rat

MiR-128-3p Alleviates Spinal Cord Ischemia/Reperfusion Injury Associated Neuroinflammation and Cellular Apoptosis via SP1 Suppression in Rat

FOXD3 confers chemo-sensitivity in ovarian cancer through a miR-335/DAAM1/myosin II axis-dependent mechanism

Long non-coding RNA H19 contributes to spinal cord ischemia/reperfusion injury through increasing neuronal pyroptosis by miR-181a-5p/HMGB1 axis

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