There are several malignancies of the digestive system(including gastric, pancreatic and colorectal cancers, and hepatocellular carcinoma), which are the most common types of cancer and a major cause of death worldwid...There are several malignancies of the digestive system(including gastric, pancreatic and colorectal cancers, and hepatocellular carcinoma), which are the most common types of cancer and a major cause of death worldwide. MicroRNA(miR)-7 is abundant in the pancreas, playing an important role in pancreatic development and endocrine function. Expression of miR-7 is downregulated in digestive system malignancies compared with normal tissue. Although there are contrasting results for miR-7 expression, almost all research reveals that miR-7 is a tumor suppressor, by targeting various genes in specific pathways. Moreover, miR-7 can target different genes simultaneously in different malignancies of the digestive system. By acting on many cytokines, miR-7 is also involved in many gastrointestinal inflammatory diseases as a significant carcinogenic factor. Consequently, miR-7 might be a biomarker or therapeutic target gene in digestive system malignancies.展开更多
AIM：To investigate the changes in the expression of micro RNA-181a（mi R-181a）and Bim in a rat model of retinal ischemia-reperfusion（RIR）,to explore their target relationship in RIR and their involvement in regula...AIM：To investigate the changes in the expression of micro RNA-181a（mi R-181a）and Bim in a rat model of retinal ischemia-reperfusion（RIR）,to explore their target relationship in RIR and their involvement in regulating apoptosis of retinal ganglion cells（RGCs）.·M ETHODS：Target gene prediction for mi R-181a was performed with the aid of bioinformatics and Bim was identified as a potential target gene of mi R-181a.A rat model of RIR was created by increasing the intraocular pressure.RGCs in the flatmounted retinas were labeled with Brn3,a marker for alive RGCs,by immunofluorescent staining.The changes in the number of RGCs after RIR were recorded.Quantitative reverse transcription-polymerase chain reaction（q RT-PCR）was used to determine the expression level of mi R-181a in the retina.Bim/Brn3 double immunofluorescence was used to detect the localization of Bim.The expression of Bim in the retina was determined with the aids of Western blot and q RT-PCR.·R ESULTS：Compared with the negative control group,the density of RGCs was significantly lower in the ischemia/reperfusion（I/R）-24h and I/R-72h groups（〈0.001）.The expression level of mi R-181a started to decrease at 0h after RIR,and further decreased at 24h and 72h compared with the negative control group（〈0.001）.Bim was significantly upregulated at 12h after RIR（〈0.05）and reached peak at 24,72h compared with the negative control group（〈0.01）.Pearson correlation analysis showed that the expression level of Bim was negatively correlated with the expression level of mi R-181a and the density of RGCs.·CONCLUSION：Bim may be a potential target gene of mi R-181a.Both mi R-181a and Bim are involved in RGCs death in RIR.RIR may promote RGCs apoptosis in the retina downregulation of mi R-181a and its inhibition on Bim expression.展开更多
Objective： Intratumoral administration of adenoviral vector encoding herpes simplex virus （HSV） thymidine kinase （TK） gene （Ad-TK） followed by systemic ganciclovir （GCV） is an effective approach in treating e...Objective： Intratumoral administration of adenoviral vector encoding herpes simplex virus （HSV） thymidine kinase （TK） gene （Ad-TK） followed by systemic ganciclovir （GCV） is an effective approach in treating experimental hepatocellular carcinoma （HCC）. However, hepatotoxicity due to unwanted vector spread and suicide gene expression limited the application of this therapy, miR-122 is an abundant, liver-specific microRNA whose expression is decreased in human primary HCC and HCC-derived cell lines. These different expression profiles provide an opportunity to induce tumor-specific gene expression by miR-122 regulation. Methods： By inserting miR-122 target sequences （miR-122T） in the 3＇ untranslated region （UTR） ofTK gene, we constructed adenovirus （Ad） vectors expressing miR-122-regulated TK （Ad-TK-122T） and report genes. After intratumoral administration of Ad vectors into an orthotopic miR-122-deficient HCC mouse model, we observed the miR-122-regulated transgene expression and assessed the antitumor activity and safety of Ad-TK-122T. Results： Insertion of miR-122T specifically down-regulated transgene expression in vitro and selectively protected the miR-122-positive cells from killing by TK/GCV treatment. Insertion of miR-122T led to significant reduction of tansgene expression in the liver without inhibition of its expression in tumors in vivo, resulting in an 11-fold improvement of tumor-specific transgene expression. Intratumoral injection of Ad vectors mediated TK/GCV system led to a vector dosage-dependent regression of tumor. The insertion of miR-122T does not influence the antitumor effects of suicide gene therapy. Whereas mice administrated with Ad-TK showed severe lethal hepatotoxicity at the effective therapeutic dose, no liver damage was found in Ad-TK-122T group. Conclusions： miR-122-regulated TK expression achieved effective anti-tumor effects and increased the safety of intratumoral delivery of adenovirus-mediated TK/GCV gene therapy for miR-122-deficient HCC.展开更多
基金Supported by National Natural Science Foundation of China,No.81273735Science and Technology Planning Project of Guangdong Province,China,No.2013B021800169Traditional Chinese Medicine Science and Technology Research Projects of Guangdong Provincial Hospital of Chinese Medicine,China,No.YN2014ZH05
文摘There are several malignancies of the digestive system(including gastric, pancreatic and colorectal cancers, and hepatocellular carcinoma), which are the most common types of cancer and a major cause of death worldwide. MicroRNA(miR)-7 is abundant in the pancreas, playing an important role in pancreatic development and endocrine function. Expression of miR-7 is downregulated in digestive system malignancies compared with normal tissue. Although there are contrasting results for miR-7 expression, almost all research reveals that miR-7 is a tumor suppressor, by targeting various genes in specific pathways. Moreover, miR-7 can target different genes simultaneously in different malignancies of the digestive system. By acting on many cytokines, miR-7 is also involved in many gastrointestinal inflammatory diseases as a significant carcinogenic factor. Consequently, miR-7 might be a biomarker or therapeutic target gene in digestive system malignancies.
基金Supported by the National Natural Science Foundation of China(No.81070742/H1205)the International Collaboration Foundation from the Department of Science and Technology of Sichuan Province,China(No.2010HH0030)
文摘AIM：To investigate the changes in the expression of micro RNA-181a（mi R-181a）and Bim in a rat model of retinal ischemia-reperfusion（RIR）,to explore their target relationship in RIR and their involvement in regulating apoptosis of retinal ganglion cells（RGCs）.·M ETHODS：Target gene prediction for mi R-181a was performed with the aid of bioinformatics and Bim was identified as a potential target gene of mi R-181a.A rat model of RIR was created by increasing the intraocular pressure.RGCs in the flatmounted retinas were labeled with Brn3,a marker for alive RGCs,by immunofluorescent staining.The changes in the number of RGCs after RIR were recorded.Quantitative reverse transcription-polymerase chain reaction（q RT-PCR）was used to determine the expression level of mi R-181a in the retina.Bim/Brn3 double immunofluorescence was used to detect the localization of Bim.The expression of Bim in the retina was determined with the aids of Western blot and q RT-PCR.·R ESULTS：Compared with the negative control group,the density of RGCs was significantly lower in the ischemia/reperfusion（I/R）-24h and I/R-72h groups（〈0.001）.The expression level of mi R-181a started to decrease at 0h after RIR,and further decreased at 24h and 72h compared with the negative control group（〈0.001）.Bim was significantly upregulated at 12h after RIR（〈0.05）and reached peak at 24,72h compared with the negative control group（〈0.01）.Pearson correlation analysis showed that the expression level of Bim was negatively correlated with the expression level of mi R-181a and the density of RGCs.·CONCLUSION：Bim may be a potential target gene of mi R-181a.Both mi R-181a and Bim are involved in RGCs death in RIR.RIR may promote RGCs apoptosis in the retina downregulation of mi R-181a and its inhibition on Bim expression.
基金funded by the National 863 Program (No.2012AA020810)Beijing city strategic emerging industry (No.Z121102002912040)
文摘Objective： Intratumoral administration of adenoviral vector encoding herpes simplex virus （HSV） thymidine kinase （TK） gene （Ad-TK） followed by systemic ganciclovir （GCV） is an effective approach in treating experimental hepatocellular carcinoma （HCC）. However, hepatotoxicity due to unwanted vector spread and suicide gene expression limited the application of this therapy, miR-122 is an abundant, liver-specific microRNA whose expression is decreased in human primary HCC and HCC-derived cell lines. These different expression profiles provide an opportunity to induce tumor-specific gene expression by miR-122 regulation. Methods： By inserting miR-122 target sequences （miR-122T） in the 3＇ untranslated region （UTR） ofTK gene, we constructed adenovirus （Ad） vectors expressing miR-122-regulated TK （Ad-TK-122T） and report genes. After intratumoral administration of Ad vectors into an orthotopic miR-122-deficient HCC mouse model, we observed the miR-122-regulated transgene expression and assessed the antitumor activity and safety of Ad-TK-122T. Results： Insertion of miR-122T specifically down-regulated transgene expression in vitro and selectively protected the miR-122-positive cells from killing by TK/GCV treatment. Insertion of miR-122T led to significant reduction of tansgene expression in the liver without inhibition of its expression in tumors in vivo, resulting in an 11-fold improvement of tumor-specific transgene expression. Intratumoral injection of Ad vectors mediated TK/GCV system led to a vector dosage-dependent regression of tumor. The insertion of miR-122T does not influence the antitumor effects of suicide gene therapy. Whereas mice administrated with Ad-TK showed severe lethal hepatotoxicity at the effective therapeutic dose, no liver damage was found in Ad-TK-122T group. Conclusions： miR-122-regulated TK expression achieved effective anti-tumor effects and increased the safety of intratumoral delivery of adenovirus-mediated TK/GCV gene therapy for miR-122-deficient HCC.
