Objective: To investigate the expression of miRNA21 in hippocampus of rats with pentylenetetrazol-induced epilepsy and its possible mechanism. Methods: Twenty-four healthy male wister rats was randomly divided into tw...Objective: To investigate the expression of miRNA21 in hippocampus of rats with pentylenetetrazol-induced epilepsy and its possible mechanism. Methods: Twenty-four healthy male wister rats was randomly divided into two groups, the normal group and the epilepsy group. The Racine grade scores of the two groups of rats were recorded to evaluate the establishment of a rat model of epilepsy. The differentially expressed of microRNAs targeting bcl-2 in the hippocampus of epileptic rats was screened by bioinformatics method. The expression of microRNA21 in hippocampus of epileptic rats was verified by qRT-PCR. Western blot and immunohistochemistry were used to detect the expression of Bcl-2 in rat hippocampus;Hoechst 33258 was used to detect the apoptosis of rat hippocampal neurons. Results: The Racine score of the rats in the epilepsy group was significantly higher than that in the normal control group (P<0.01). Compared with the normal group, the expression of miRNA21 in the hippocampus of the epileptic group increased (P<0.01) and the expression of Bcl-2 decreased (P<0.01). Conclusion: Epilepsy can up-regulate the expression of miRNA21 in rat hippocampal neurons, and it may further induce apoptosis of hippocampal neurons by down-regulating Bcl-2, which may affect epileptic rats.展开更多
Oncogenic microRNAs are essential components in regulating the gene expression of cancer cells. Especially miR21, which is a major player involved of tumor initiation, progression, invasion and metastasis in several c...Oncogenic microRNAs are essential components in regulating the gene expression of cancer cells. Especially miR21, which is a major player involved of tumor initiation, progression, invasion and metastasis in several cancers. The delivery of anti-miR21 sequences has significant potential for cancer treatment. Nevertheless, since anti-miR21 sequences are extremely unstable and they need to obtain certain concentration to function, it is intensely difficult to build an effective delivery system for them.The purpose of this work is to construct a self-assembled glutathione(GSH)-responsive system with tumor accumulation capacity for effective anti-miR21 delivery and cancer therapy. A novel drug delivery nanosphere carrying millions of anti-miR21 sequences was developed through the rolling circle transcription(RCT) method. GSH-responsive cationic polymer polyethyleneimine(pOEI) was synthesized to protect the nanosphere from degradation by Dicer or other RNase in normal cells and optimize the pompon-like nanoparticle to suitable size. Dehydroascorbic acid(DHA), a targeting molecule, which is a substrate of glucose transporter 1(GLUT 1) and highly expressed on malignant tumor cells, was connected to pOEI through PEG, and then the polymer was used for contracting a RNA nanospheres into nanopompons. The anti-miR21 nanopompons showed its potential for effective cancer therapy.展开更多
文摘Objective: To investigate the expression of miRNA21 in hippocampus of rats with pentylenetetrazol-induced epilepsy and its possible mechanism. Methods: Twenty-four healthy male wister rats was randomly divided into two groups, the normal group and the epilepsy group. The Racine grade scores of the two groups of rats were recorded to evaluate the establishment of a rat model of epilepsy. The differentially expressed of microRNAs targeting bcl-2 in the hippocampus of epileptic rats was screened by bioinformatics method. The expression of microRNA21 in hippocampus of epileptic rats was verified by qRT-PCR. Western blot and immunohistochemistry were used to detect the expression of Bcl-2 in rat hippocampus;Hoechst 33258 was used to detect the apoptosis of rat hippocampal neurons. Results: The Racine score of the rats in the epilepsy group was significantly higher than that in the normal control group (P<0.01). Compared with the normal group, the expression of miRNA21 in the hippocampus of the epileptic group increased (P<0.01) and the expression of Bcl-2 decreased (P<0.01). Conclusion: Epilepsy can up-regulate the expression of miRNA21 in rat hippocampal neurons, and it may further induce apoptosis of hippocampal neurons by down-regulating Bcl-2, which may affect epileptic rats.
基金supported by the grants from National Science Fund for Distinguished Young Scholars(81425023,China)Program of Shanghai Academic Research Leader(18XD1400500,China)
文摘Oncogenic microRNAs are essential components in regulating the gene expression of cancer cells. Especially miR21, which is a major player involved of tumor initiation, progression, invasion and metastasis in several cancers. The delivery of anti-miR21 sequences has significant potential for cancer treatment. Nevertheless, since anti-miR21 sequences are extremely unstable and they need to obtain certain concentration to function, it is intensely difficult to build an effective delivery system for them.The purpose of this work is to construct a self-assembled glutathione(GSH)-responsive system with tumor accumulation capacity for effective anti-miR21 delivery and cancer therapy. A novel drug delivery nanosphere carrying millions of anti-miR21 sequences was developed through the rolling circle transcription(RCT) method. GSH-responsive cationic polymer polyethyleneimine(pOEI) was synthesized to protect the nanosphere from degradation by Dicer or other RNase in normal cells and optimize the pompon-like nanoparticle to suitable size. Dehydroascorbic acid(DHA), a targeting molecule, which is a substrate of glucose transporter 1(GLUT 1) and highly expressed on malignant tumor cells, was connected to pOEI through PEG, and then the polymer was used for contracting a RNA nanospheres into nanopompons. The anti-miR21 nanopompons showed its potential for effective cancer therapy.
