Objective:Overexpression of microRNA-21(miR-21)has been well-recognized during fibrosis in a wide range of tissue types through regulation of fibrogenesis via diverse pathways.Curcumin exhibits antifibrotic effects in...Objective:Overexpression of microRNA-21(miR-21)has been well-recognized during fibrosis in a wide range of tissue types through regulation of fibrogenesis via diverse pathways.Curcumin exhibits antifibrotic effects in various organs.We and others have previously demonstrated that curcumin has positive effects on the protection against fibrosis.However,the effect of curcumin on miR-21 expression has not been reported.Methods:In this study,transforming growth factor-b1(TGF-b1)-stimulated rat renal fibroblast cells(NRK-49F)were transfected with miR-21 inhibitors,then the expression of Smad3,a-smooth muscle actin(a-SMA),type I collagen(COL1A1),and type III collagen(COL3A1)was determined using quantitative real-time-PCR(qRT-PCR)and western blot analysis.The effect of curcumin on production of the extracellular matrix was evaluated using immunofluorescence,qRT-PCR,and western blot analysis.Results:TGF-b1 stimulation upregulated the expression of miR-21 and induced fibrogenesis in NRK-49F cells.Transfection with miR-21 inhibitors selectively decreased smad3 activity,and noticeably reduced the expression of a-SMA,COL1A1,and COL3A1.Curcumin treatment significantly inhibited the expressions of smad3,a-SMA,COL1A1,COL3A1,as well as miR-21 expression in NRK-49F cells in a dosedependent manner.Conclusion:Curcumin exerted its anti-fibrotic effects by targeting the TGF-b1/smad3 signaling pathway and suppressing miR-21 expression,thereby provides novel insight in the protective effects of curcumin against fibrosis in various organs.展开更多
Acrylamide, a potential carcinogen, exists in carbohydrate-rich foods cooked at a high temperature. It has been reported that acrylamide can cause DNA damage and cytotoxicity. The present study aimed to investigate th...Acrylamide, a potential carcinogen, exists in carbohydrate-rich foods cooked at a high temperature. It has been reported that acrylamide can cause DNA damage and cytotoxicity. The present study aimed to investigate the potential mechanism of human hepatocarcinoma HepG2 cell proliferation induced by acrylamide and to explore the antagonistic effects of a natural polyphenol curcumin against acrylamide via miR-21. The results indicated that acrylamide(≤100μmol/L) significantly increased HepG2 cell proliferation and miR-21 expression. In addition, acrylamide reduced the PTEN expression in protein level, while induced the expressions of p-AKT, EGFR and cyclin D1. The PI3 K/AKT inhibitor decreased p-AKT protein expression and inhibited the proliferation of HepG2 cells. In addition, curcumin effectively reduced acrylamide-induced HepG2 cell proliferation and induced apoptosis through the expression of miR-21. In conclusion, the results showed that acrylamide increased HepG2 cell proliferation via upregulating miR-21 expression, which may be a new target for the treatment and prevention of cancer.展开更多
Objective:To systematically evaluate the relationship between the miR-21 level in peripheral blood and hypertension.Methods:A systematic literature searching of CNKI,Wanfang and VIP databases,PubMed,Web of Science and...Objective:To systematically evaluate the relationship between the miR-21 level in peripheral blood and hypertension.Methods:A systematic literature searching of CNKI,Wanfang and VIP databases,PubMed,Web of Science and EMBASE by keywords was performed up to the end of November 2020.All statistical analysis was performed using the state16.0 software.Results:A total of 9 studies including 577 hypertension patients and 344 healthy controls were selected.The combined effect SMD was 1.53(95%CI:0.58-2.47,P=0.002).It is suggested that the level of miR-21 in peripheral blood of patients with hypertension is higher than that of controls.In subgroup analysis,the level of miR-21 in peripheral blood mononuclear cells(PBMC)in hypertensives was higher than that in controls(SMD=3.49,95%CI:1.24-5.74),and the difference was statistically significant(P=0.002).But the association was not found in plasma(P=0.375).No publication bias was found in our study by Begg's funnel plot and Egger's test.Conclusion:The increased level of miR-21 in peripheral blood,especially in PBMC,is a risk factor for hypertension.Limited by the number of included studies,the conclusion still needs to be verified by more high-quality studies.展开更多
miRNAs play an important regulatory role in variety of cellular functions and several diseases, including cancer. MicroRNA-21 (miR-21) is overexpressed in almost all types of human cancers. Studies revealed that the k...miRNAs play an important regulatory role in variety of cellular functions and several diseases, including cancer. MicroRNA-21 (miR-21) is overexpressed in almost all types of human cancers. Studies revealed that the knockdown of miR-21 results in reduced tumor cell growth, cell cycle arrest and cell apoptosis. In this study, we evaluated the effect of doxorubicin on miR-21 expression in mcf-7 breast cancer cells. miRNA was extracted from mcf-7 cells treated with doxorubicin and untreated cells using miRNeasy Kit (Qiagen) according to the manufacturer’s instructions. cDNA synthesis was performed using miScript II RT Kit (Qiagen) and Real Time-PCR was performed using Real Q Plus 2x Master Mix Green-(Ampliqon, Denmark). The relative expression of miR-16 and miR-21 was calculated using comparative Ct method. All tests were run in triplicate to minimize the experimental errors. Samples with a Ct > 37 were excluded from the analysis. Statistically, a significant decrease in cell proliferation of mcf-7 cells was found in doxorubicin group compared with control groups 24 hours after transfection, dose dependently (p value< 0.001). After 24 hours, Doxorubicin (100 μm) significantly decreased miR-21 expression in mcf-7 cells (p = 0.0001). Also, the expression of caspase 9 significantly increased after Doxorubicin (100 μm) treatment (p = 0.0003). Together, these findings indicate that miR-21 plays a key role in regulating cell apoptosis in mcf-7 cells and may serve as a target for effective therapies.展开更多
Objective: To study the miR-21 expression in bladder cancer lesion and its effect on cancer cell invasion and angiogenesis. Methods: A total of 94 patients with bladder cancer who received surgical resection in our ho...Objective: To study the miR-21 expression in bladder cancer lesion and its effect on cancer cell invasion and angiogenesis. Methods: A total of 94 patients with bladder cancer who received surgical resection in our hospital between February 2015 and June 2017 were selected as the research subjects, and proper amount of bladder cancer lesion and adjacent lesion were collected to detect the expression of miR-21 as well as the mRNA expression of invasion genes and angiogenesis genes. Results: miR-21 expression in bladder cancer lesion was significantly higher than that in adjacent lesion;CDH13 and CBX7 mRNA expression in bladder cancer lesion were significantly lower than those in adjacent lesion while TRAP-1, KPNA2, TRPM8, EDIL3, HGF, VEGF and Epha2 mRNA expression were significantly higher than those in adjacent lesion. CDH13 and CBX7 mRNA expression in bladder cancer lesion with high miR-21 expression were significantly lower than those in bladder cancer lesion with low miR-21 expression while TRAP-1, KPNA2, TRPM8, EDIL3, HGF, VEGF and Epha2 mRNA expression were significantly higher than those in bladder cancer lesion with low miR-21 expression. Conclusion: The high expression of miR-21 in bladder cancer can promote the invasion of cancer cells and the angiogenesis in the lesion.展开更多
The functional properties of endogenous Schwann cells(SCs)during nerve repair are dynamic.Optimizing the functional properties of SCs at different stages of nerve repair may have therapeutic benefit in improving the r...The functional properties of endogenous Schwann cells(SCs)during nerve repair are dynamic.Optimizing the functional properties of SCs at different stages of nerve repair may have therapeutic benefit in improving the repair of damaged nerves.Previous studies showed that miR-221-3p promotes the proliferation and migration of SCs,and miR-338-3p promotes the myelination of SCs.In this study,we established rat models of sciatic nerve injury by bridging the transected sciatic nerve with a silicone tube.We injected a miR-221 lentiviral vector system together with a doxycycline-inducible Tet-On miR-338 lentiviral vector system into the cavity of nerve conduits of nerve stumps to sequentially regulate the biological function of endogenous SCs at different stages of nerve regeneration.We found that the biological function of SCs was sequentially regulated,the diameter and density of myelinated axons were increased,the expression levels of NF200 and myelin basic protein were increased,and the function of injured peripheral nerve was improved using this system.miRNA Target Prediction Database prediction,Nanopore whole transcriptome sequencing,quantitative PCR,and dual luciferase reporter gene assay results predicted and verified Cdkn1b and Nrp1 as target genes of miR-221-3p and miR-338-3p,respectively,and their regulatory effects on SCs were confirmed in vitro.In conclusion,here we established a new method to enhance nerve regeneration through sequential regulation of biological functions of endogenous SCs,which establishes a new concept and model for the treatment of peripheral nerve injury.The findings from this study will provide direct guiding significance for clinical treatment of sciatic nerve injury.展开更多
基金This study was supported by the National Natural Science Foundation of China of China(No.81573716).
文摘Objective:Overexpression of microRNA-21(miR-21)has been well-recognized during fibrosis in a wide range of tissue types through regulation of fibrogenesis via diverse pathways.Curcumin exhibits antifibrotic effects in various organs.We and others have previously demonstrated that curcumin has positive effects on the protection against fibrosis.However,the effect of curcumin on miR-21 expression has not been reported.Methods:In this study,transforming growth factor-b1(TGF-b1)-stimulated rat renal fibroblast cells(NRK-49F)were transfected with miR-21 inhibitors,then the expression of Smad3,a-smooth muscle actin(a-SMA),type I collagen(COL1A1),and type III collagen(COL3A1)was determined using quantitative real-time-PCR(qRT-PCR)and western blot analysis.The effect of curcumin on production of the extracellular matrix was evaluated using immunofluorescence,qRT-PCR,and western blot analysis.Results:TGF-b1 stimulation upregulated the expression of miR-21 and induced fibrogenesis in NRK-49F cells.Transfection with miR-21 inhibitors selectively decreased smad3 activity,and noticeably reduced the expression of a-SMA,COL1A1,and COL3A1.Curcumin treatment significantly inhibited the expressions of smad3,a-SMA,COL1A1,COL3A1,as well as miR-21 expression in NRK-49F cells in a dosedependent manner.Conclusion:Curcumin exerted its anti-fibrotic effects by targeting the TGF-b1/smad3 signaling pathway and suppressing miR-21 expression,thereby provides novel insight in the protective effects of curcumin against fibrosis in various organs.
基金supported by the National Natural Science Foundation of China (81472977) foundation from the Priority Academic Program Development of Jiangsu Higher Education Institutions Graduate Student Practice and Innovation Project of Jiangsu Province Ordinary University (SJZZ15_0117)
文摘Acrylamide, a potential carcinogen, exists in carbohydrate-rich foods cooked at a high temperature. It has been reported that acrylamide can cause DNA damage and cytotoxicity. The present study aimed to investigate the potential mechanism of human hepatocarcinoma HepG2 cell proliferation induced by acrylamide and to explore the antagonistic effects of a natural polyphenol curcumin against acrylamide via miR-21. The results indicated that acrylamide(≤100μmol/L) significantly increased HepG2 cell proliferation and miR-21 expression. In addition, acrylamide reduced the PTEN expression in protein level, while induced the expressions of p-AKT, EGFR and cyclin D1. The PI3 K/AKT inhibitor decreased p-AKT protein expression and inhibited the proliferation of HepG2 cells. In addition, curcumin effectively reduced acrylamide-induced HepG2 cell proliferation and induced apoptosis through the expression of miR-21. In conclusion, the results showed that acrylamide increased HepG2 cell proliferation via upregulating miR-21 expression, which may be a new target for the treatment and prevention of cancer.
基金The fifth batch of talents selected from the"Special Support Plan"of Anhui Province(No.[2019]14)NSFC(No.81874280)+1 种基金Natural Science Foundation of Anhui Province(No.1808085QH283)Key Natural Science Research Project of Anhui Provincial Education Department(No.KJ2019A0404,KJ2019A0405)。
文摘Objective:To systematically evaluate the relationship between the miR-21 level in peripheral blood and hypertension.Methods:A systematic literature searching of CNKI,Wanfang and VIP databases,PubMed,Web of Science and EMBASE by keywords was performed up to the end of November 2020.All statistical analysis was performed using the state16.0 software.Results:A total of 9 studies including 577 hypertension patients and 344 healthy controls were selected.The combined effect SMD was 1.53(95%CI:0.58-2.47,P=0.002).It is suggested that the level of miR-21 in peripheral blood of patients with hypertension is higher than that of controls.In subgroup analysis,the level of miR-21 in peripheral blood mononuclear cells(PBMC)in hypertensives was higher than that in controls(SMD=3.49,95%CI:1.24-5.74),and the difference was statistically significant(P=0.002).But the association was not found in plasma(P=0.375).No publication bias was found in our study by Begg's funnel plot and Egger's test.Conclusion:The increased level of miR-21 in peripheral blood,especially in PBMC,is a risk factor for hypertension.Limited by the number of included studies,the conclusion still needs to be verified by more high-quality studies.
文摘miRNAs play an important regulatory role in variety of cellular functions and several diseases, including cancer. MicroRNA-21 (miR-21) is overexpressed in almost all types of human cancers. Studies revealed that the knockdown of miR-21 results in reduced tumor cell growth, cell cycle arrest and cell apoptosis. In this study, we evaluated the effect of doxorubicin on miR-21 expression in mcf-7 breast cancer cells. miRNA was extracted from mcf-7 cells treated with doxorubicin and untreated cells using miRNeasy Kit (Qiagen) according to the manufacturer’s instructions. cDNA synthesis was performed using miScript II RT Kit (Qiagen) and Real Time-PCR was performed using Real Q Plus 2x Master Mix Green-(Ampliqon, Denmark). The relative expression of miR-16 and miR-21 was calculated using comparative Ct method. All tests were run in triplicate to minimize the experimental errors. Samples with a Ct > 37 were excluded from the analysis. Statistically, a significant decrease in cell proliferation of mcf-7 cells was found in doxorubicin group compared with control groups 24 hours after transfection, dose dependently (p value< 0.001). After 24 hours, Doxorubicin (100 μm) significantly decreased miR-21 expression in mcf-7 cells (p = 0.0001). Also, the expression of caspase 9 significantly increased after Doxorubicin (100 μm) treatment (p = 0.0003). Together, these findings indicate that miR-21 plays a key role in regulating cell apoptosis in mcf-7 cells and may serve as a target for effective therapies.
文摘Objective: To study the miR-21 expression in bladder cancer lesion and its effect on cancer cell invasion and angiogenesis. Methods: A total of 94 patients with bladder cancer who received surgical resection in our hospital between February 2015 and June 2017 were selected as the research subjects, and proper amount of bladder cancer lesion and adjacent lesion were collected to detect the expression of miR-21 as well as the mRNA expression of invasion genes and angiogenesis genes. Results: miR-21 expression in bladder cancer lesion was significantly higher than that in adjacent lesion;CDH13 and CBX7 mRNA expression in bladder cancer lesion were significantly lower than those in adjacent lesion while TRAP-1, KPNA2, TRPM8, EDIL3, HGF, VEGF and Epha2 mRNA expression were significantly higher than those in adjacent lesion. CDH13 and CBX7 mRNA expression in bladder cancer lesion with high miR-21 expression were significantly lower than those in bladder cancer lesion with low miR-21 expression while TRAP-1, KPNA2, TRPM8, EDIL3, HGF, VEGF and Epha2 mRNA expression were significantly higher than those in bladder cancer lesion with low miR-21 expression. Conclusion: The high expression of miR-21 in bladder cancer can promote the invasion of cancer cells and the angiogenesis in the lesion.
基金supported by the National Natural Science Foundation of China,No.81771351the National Key R&D Program of China,No.2017YFA0105802+1 种基金the Joint Research Fund Liaoning-Shenyang National Laboratory for Materials Science,No.2019JH3/30100022the National Science Foundation for Post-doctoral Scientists of China,No.2018M641732(all to QA and LLW)。
文摘The functional properties of endogenous Schwann cells(SCs)during nerve repair are dynamic.Optimizing the functional properties of SCs at different stages of nerve repair may have therapeutic benefit in improving the repair of damaged nerves.Previous studies showed that miR-221-3p promotes the proliferation and migration of SCs,and miR-338-3p promotes the myelination of SCs.In this study,we established rat models of sciatic nerve injury by bridging the transected sciatic nerve with a silicone tube.We injected a miR-221 lentiviral vector system together with a doxycycline-inducible Tet-On miR-338 lentiviral vector system into the cavity of nerve conduits of nerve stumps to sequentially regulate the biological function of endogenous SCs at different stages of nerve regeneration.We found that the biological function of SCs was sequentially regulated,the diameter and density of myelinated axons were increased,the expression levels of NF200 and myelin basic protein were increased,and the function of injured peripheral nerve was improved using this system.miRNA Target Prediction Database prediction,Nanopore whole transcriptome sequencing,quantitative PCR,and dual luciferase reporter gene assay results predicted and verified Cdkn1b and Nrp1 as target genes of miR-221-3p and miR-338-3p,respectively,and their regulatory effects on SCs were confirmed in vitro.In conclusion,here we established a new method to enhance nerve regeneration through sequential regulation of biological functions of endogenous SCs,which establishes a new concept and model for the treatment of peripheral nerve injury.The findings from this study will provide direct guiding significance for clinical treatment of sciatic nerve injury.
