Early reperfusion of ischemic cardiac tissue is usually the best option to improve clinical outcome of angina pectoris, especially of acute myocardial infarction. However, myocardial reperfusion may cause an abnormal ...Early reperfusion of ischemic cardiac tissue is usually the best option to improve clinical outcome of angina pectoris, especially of acute myocardial infarction. However, myocardial reperfusion may cause an abnormal increase of intracellular Ca^2+-mediated cardiomyocyte death and consequent loss of cardiac function, which is referred to myocardial ischemia/reperfusion (I/R) injury. Recently, the microRNA-214 (miR-214)/Na^+/Ca^2+ exchanger (NCX) 1 co-expression is a key factor in cellular protection against myocardial apoptosis for myocardial I/R injury. Once activated, miR-214/NCX1 axis can inhibit several Ca^2+ downstream signaling effectors that mediate cell death simultaneously. Studies have shown that acupuncture preconditioning has a protective effect on myocardial I/R injury, but its mechanism deserves further research. It has been proved that acupuncture preconditioning for ischemic myocardium successfully inhibit multiple Ca2+ handling related microRNAs that mediate cell death pathways, and miR-214 is one of its targets. In terms of clinical practice, coronary heart disease (CHD) patients benefit a lot from this intervention. However, there is barely no study correlating acupuncture preconditioning to the miR-214/NCX1 co-expression in patients with CHD. This review aims to discuss whether there is some evidence to justify a recommendation of acupuncture preconditioning in CHD patients as a non-pharmacological therapeutic method to activate the miR-214/NCX1 co-expression network model.展开更多
Research has shown that long-chain noncoding RNAs(lncRNAs) are involved in the regulation of a variety of biological processes, including peripheral nerve regeneration, in part by acting as competing endogenous RNAs. ...Research has shown that long-chain noncoding RNAs(lncRNAs) are involved in the regulation of a variety of biological processes, including peripheral nerve regeneration, in part by acting as competing endogenous RNAs. c-Jun plays a key role in the repair of peripheral nerve injury. However, the precise underlying mechanism of c-Jun remains unclear. In this study, we performed microarray and bioinformatics analysis of mouse crush-injured sciatic nerves and found that the lncRNA Pvt1 was overexpressed in Schwann cells after peripheral nerve injury. Mechanistic studies revealed that Pvt1 increased c-Jun expression through sponging miRNA-214. We overexpressed Pvt1 in Schwann cells cultured in vitro and found that the proliferation and migration of Schwann cells were enhanced, and overexpression of miRNA-214 counteracted the effects of Pvt1 overexpression on Schwann cell proliferation and migration. We conducted in vivo analyses and injected Schwann cells overexpressing Pvt1 into injured sciatic nerves of mice. Schwann cells overexpressing Pvt1 enhanced the regeneration of injured sciatic nerves following peripheral nerve injury and the locomotor function of mice was improved. Our findings reveal the role of lncRNAs in the repair of peripheral nerve injury and highlight lncRNA Pvt1 as a novel potential treatment target for peripheral nerve injury.展开更多
A tumor suppressor gene, CADM1, encoding an immunoglobulin superfamily cell adhesion molecule, is inactivated in various cancers, including non-small-cell lung cancer (NSCLC). Although promoter methylation is one of t...A tumor suppressor gene, CADM1, encoding an immunoglobulin superfamily cell adhesion molecule, is inactivated in various cancers, including non-small-cell lung cancer (NSCLC). Although promoter methylation is one of the mechanisms to suppress CADM1 expression, about half of tumors lacking CADM1 expression do not show methylation of the gene promoter. We herein investigated the possible involvement of microRNA (miRNA) in the down-regulation of CADM1. Using computational algorithms, miR-214 and miR-375 were identified as candidate miRNAs targeting CADM1. A luciferase reporter assay demonstrated that miR-214 and miR-375 repressed the promoter activity through 3’-UTR of CADM1. Quantitative RT-PCR analysis demonstrated that miR-214 and miR-375 was highly expressed in 21 (62%) and 17 cases (50%) of 34 primary NSCLCs. Notably, increased expression of miR-214 was preferentially observed in tumors with advanced pathological stages and in those lacking CADM1 expression but were not associated with the promoter methylation, suggesting that miR-214-mediated silencing would be another mechanism to suppress CADM1 expression. On the other hand, introduction of miR-214 or miR-375 into NSCLC cells decreased CADM1 protein expression. Furthermore, overexpression of miR-214 enhanced anchorage-independent growth of NSCLC cells, A549, whereas transfection of miRNA inhibitor, miR-214 or miR-375, significantly suppressed the in vitro wound healing activity of HCC827 cells. These findings suggest that overexpression of miR-214 and miR-375 could participate in the malignant features of NSCLC through down-regulating CADM1 and would provide a potential target for the treatment of a subset of NSCLC.展开更多
Objective:To investigate the mechanism of mir-214-mediated HIF1 alpha and KIM1 signaling pathways in rats with ischemic acute kidney injury. Methods:Rats were divided into three groups according to the difference of t...Objective:To investigate the mechanism of mir-214-mediated HIF1 alpha and KIM1 signaling pathways in rats with ischemic acute kidney injury. Methods:Rats were divided into three groups according to the difference of the preparation model, 16 in each group, sham operation group, IAKI group and miR-214 group.The rats in the latter two groups were established with ischemic acute kidney injury. After 48 hours, three groups of rats were treated with orbital venous blood. Urine was collected, biochemical parameters and KIM1 expression were detected. After using Masson's Trichrome, TUNEL, immunoblotting and PCR, renal histopathology, apoptosis of glomerular epithelial cells and expression of HIF1α, KIM1 protein and mRNA in renal tissues were detected. Results:The biochemical parameters of rats in the IAKI group included Scr, BUN and 24hUTP, which were higher than the previous group (P<0.05). The MIR-214 group was higher than the IAKI group. The sham operation group had intact renal tissue structure and good renal tubular and glomeruli. The IAKIgroup had increased glomerular interstitial, renal interstitial widening and inflammation. Severe infiltration, severe tubular atrophy, miR-214 group and IAKIgroup, renal interstitial inflammation increased, hardness increased, tubular atrophy more serious;black yellow is apoptotic cells, IAKIgroup rat renal tubular epithelial cell apoptosis The most serious, the degree of apoptosis was significantly higher than the sham operation group;the degree of apoptosis of renal tubular epithelial cells was increased in the miR-214 group compared with the IAKIgroup, and high levels of miR-214 could accelerate the apoptosis of epithelial cellsThe HIF1α and KIM1 proteins in the IAKI group were higher than those in the Previous group(P<0.05). The above indexes in the mir-214 group were better than those in the IAKI group(P<0.05). The HIF1α and KIM1 mRNA in the IAKI group were higher than in the sham operation group, and the above indicators in the mir-214 group(P<0.05). Better than the IAKI group(P<0.05);Conclusions:The increase of miR-214 accelerates the apoptosis of glomerular epithelial cells, impaired renal tissue damage, and mediates the elevation of HIF1α and KIM1, further aggravating the condition of IAKI rats.展开更多
基金the Natural Science Foundation of Inner Mongolia Autonomous Region in China (Grant No.2018MS08043)the National Natural Science Foundation of China (Grant No.81573885)+1 种基金Project of Huhhot Science and Technology (Grant No.2018-Sociology-1-3)Research Project of Health and Family Planning Commission of Inner Mongolia in China (Grant No.201703145).
文摘Early reperfusion of ischemic cardiac tissue is usually the best option to improve clinical outcome of angina pectoris, especially of acute myocardial infarction. However, myocardial reperfusion may cause an abnormal increase of intracellular Ca^2+-mediated cardiomyocyte death and consequent loss of cardiac function, which is referred to myocardial ischemia/reperfusion (I/R) injury. Recently, the microRNA-214 (miR-214)/Na^+/Ca^2+ exchanger (NCX) 1 co-expression is a key factor in cellular protection against myocardial apoptosis for myocardial I/R injury. Once activated, miR-214/NCX1 axis can inhibit several Ca^2+ downstream signaling effectors that mediate cell death simultaneously. Studies have shown that acupuncture preconditioning has a protective effect on myocardial I/R injury, but its mechanism deserves further research. It has been proved that acupuncture preconditioning for ischemic myocardium successfully inhibit multiple Ca2+ handling related microRNAs that mediate cell death pathways, and miR-214 is one of its targets. In terms of clinical practice, coronary heart disease (CHD) patients benefit a lot from this intervention. However, there is barely no study correlating acupuncture preconditioning to the miR-214/NCX1 co-expression in patients with CHD. This review aims to discuss whether there is some evidence to justify a recommendation of acupuncture preconditioning in CHD patients as a non-pharmacological therapeutic method to activate the miR-214/NCX1 co-expression network model.
基金supported by the National Natural Science Foundation of China,No. 81801213 (to BP)Xuzhou Special Fund for Promoting Scientific and Technological Innovation,Nos. KC21177 (to BP),KC21195 (to HF)Science and Technology Project of Yili Kazak Autonomous Prefecture,No. YZ2019D006 (to HF)。
文摘Research has shown that long-chain noncoding RNAs(lncRNAs) are involved in the regulation of a variety of biological processes, including peripheral nerve regeneration, in part by acting as competing endogenous RNAs. c-Jun plays a key role in the repair of peripheral nerve injury. However, the precise underlying mechanism of c-Jun remains unclear. In this study, we performed microarray and bioinformatics analysis of mouse crush-injured sciatic nerves and found that the lncRNA Pvt1 was overexpressed in Schwann cells after peripheral nerve injury. Mechanistic studies revealed that Pvt1 increased c-Jun expression through sponging miRNA-214. We overexpressed Pvt1 in Schwann cells cultured in vitro and found that the proliferation and migration of Schwann cells were enhanced, and overexpression of miRNA-214 counteracted the effects of Pvt1 overexpression on Schwann cell proliferation and migration. We conducted in vivo analyses and injected Schwann cells overexpressing Pvt1 into injured sciatic nerves of mice. Schwann cells overexpressing Pvt1 enhanced the regeneration of injured sciatic nerves following peripheral nerve injury and the locomotor function of mice was improved. Our findings reveal the role of lncRNAs in the repair of peripheral nerve injury and highlight lncRNA Pvt1 as a novel potential treatment target for peripheral nerve injury.
文摘A tumor suppressor gene, CADM1, encoding an immunoglobulin superfamily cell adhesion molecule, is inactivated in various cancers, including non-small-cell lung cancer (NSCLC). Although promoter methylation is one of the mechanisms to suppress CADM1 expression, about half of tumors lacking CADM1 expression do not show methylation of the gene promoter. We herein investigated the possible involvement of microRNA (miRNA) in the down-regulation of CADM1. Using computational algorithms, miR-214 and miR-375 were identified as candidate miRNAs targeting CADM1. A luciferase reporter assay demonstrated that miR-214 and miR-375 repressed the promoter activity through 3’-UTR of CADM1. Quantitative RT-PCR analysis demonstrated that miR-214 and miR-375 was highly expressed in 21 (62%) and 17 cases (50%) of 34 primary NSCLCs. Notably, increased expression of miR-214 was preferentially observed in tumors with advanced pathological stages and in those lacking CADM1 expression but were not associated with the promoter methylation, suggesting that miR-214-mediated silencing would be another mechanism to suppress CADM1 expression. On the other hand, introduction of miR-214 or miR-375 into NSCLC cells decreased CADM1 protein expression. Furthermore, overexpression of miR-214 enhanced anchorage-independent growth of NSCLC cells, A549, whereas transfection of miRNA inhibitor, miR-214 or miR-375, significantly suppressed the in vitro wound healing activity of HCC827 cells. These findings suggest that overexpression of miR-214 and miR-375 could participate in the malignant features of NSCLC through down-regulating CADM1 and would provide a potential target for the treatment of a subset of NSCLC.
文摘Objective:To investigate the mechanism of mir-214-mediated HIF1 alpha and KIM1 signaling pathways in rats with ischemic acute kidney injury. Methods:Rats were divided into three groups according to the difference of the preparation model, 16 in each group, sham operation group, IAKI group and miR-214 group.The rats in the latter two groups were established with ischemic acute kidney injury. After 48 hours, three groups of rats were treated with orbital venous blood. Urine was collected, biochemical parameters and KIM1 expression were detected. After using Masson's Trichrome, TUNEL, immunoblotting and PCR, renal histopathology, apoptosis of glomerular epithelial cells and expression of HIF1α, KIM1 protein and mRNA in renal tissues were detected. Results:The biochemical parameters of rats in the IAKI group included Scr, BUN and 24hUTP, which were higher than the previous group (P<0.05). The MIR-214 group was higher than the IAKI group. The sham operation group had intact renal tissue structure and good renal tubular and glomeruli. The IAKIgroup had increased glomerular interstitial, renal interstitial widening and inflammation. Severe infiltration, severe tubular atrophy, miR-214 group and IAKIgroup, renal interstitial inflammation increased, hardness increased, tubular atrophy more serious;black yellow is apoptotic cells, IAKIgroup rat renal tubular epithelial cell apoptosis The most serious, the degree of apoptosis was significantly higher than the sham operation group;the degree of apoptosis of renal tubular epithelial cells was increased in the miR-214 group compared with the IAKIgroup, and high levels of miR-214 could accelerate the apoptosis of epithelial cellsThe HIF1α and KIM1 proteins in the IAKI group were higher than those in the Previous group(P<0.05). The above indexes in the mir-214 group were better than those in the IAKI group(P<0.05). The HIF1α and KIM1 mRNA in the IAKI group were higher than in the sham operation group, and the above indicators in the mir-214 group(P<0.05). Better than the IAKI group(P<0.05);Conclusions:The increase of miR-214 accelerates the apoptosis of glomerular epithelial cells, impaired renal tissue damage, and mediates the elevation of HIF1α and KIM1, further aggravating the condition of IAKI rats.
