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
Tumor progression is usually characterized by proliferation,migration,and angiogenesis,which is essential for supplying both nutrients and oxygen to the tumor cells.Therefore,targeting angiogenesis has been considered...Tumor progression is usually characterized by proliferation,migration,and angiogenesis,which is essential for supplying both nutrients and oxygen to the tumor cells.Therefore,targeting angiogenesis has been considered a promising therapeutic strategy for cancer prevention and treatment.In the present study,we demonstrated that in addition to suppressing lung cancer cell proliferation and migration in vitro,10-hydroxycamptothecin(10-HCPT)is also capable of inhibiting angiogenesis in vivo with a miR-181a-dependent manner.Mechanistically,by upregulating miR-181a,which in turn downregulating FOXP1,10-HCPT can inhibit the PI3K/Akt/ERK signaling pathwaymediated angiogenesis.Furthermore,reduced levels of miR-181a have been found in both lung cancer cell lines and xenograft with concurrently elevated levels of FOXP1,VEGF,bFGF,and HDGF.Consistent with the findings from the in vitro experiments,miR-181a impairs neovascularization in our xenograft model.In summary,our findings have not only established the anti-oncogenic role of miR-181a in lung cancer angiogenesis but also suggest that 10-HCPT could be a potential therapeutic reagent for lung cancer treatment.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)has been a pervasive malignancy throughout the world with elevated mortality.Efficient therapeutic targets are beneficial to treat and predict the disease.Currently,the exact mo...BACKGROUND Hepatocellular carcinoma(HCC)has been a pervasive malignancy throughout the world with elevated mortality.Efficient therapeutic targets are beneficial to treat and predict the disease.Currently,the exact molecular mechanisms leading to the progression of HCC are still unclear.Research has shown that the microRNA-142-3p level decreases in HCC,whereas bioinformatics analysis of the cancer genome atlas database shows the ASH1L expression increased among liver tumor tissues.In this paper,we will explore the effects and mechanisms of microRNA-142-3p and ASH1L affect the prognosis of HCC patients and HCC cell bioactivity,and the association between them.AIM To investigate the effects and mechanisms of microRNA-142-3p and ASH1L on the HCC cell bioactivity and prognosis of HCC patients.METHODS In this study,we grouped HCC patients according to their immunohistochemistry results of ASH1L with pathological tissues,and retrospectively analyzed the prognosis of HCC patients.Furthermore,explored the roles and mechanisms of microRNA-142-3p and ASH1L by cellular and animal experiments,which involved the following experimental methods:Immunohistochemical staining,western blot,quantitative real-time-polymerase chain reaction,flow cytometric analysis,tumor xenografts in nude mice,etc.The statistical methods involved in this study contained t-test,one-way analysis of variance,theχ^(2)test,the Kaplan-Meier approach and the log-rank test.RESULTS In this study,we found that HCC patients with high expression of ASH1L possess a more recurrence rate as well as a decreased overall survival rate.ASH1L promotes the tumorigenicity of HCC and microRNA-142-3p exhibits reduced expression in HCC tissues and interacts with ASH1L through targeting the ASH1L 3′untranslated region.Furthermore,microRNA-142-3p promotes apoptosis and inhibits proliferation,invasion,and migration of HCC cell lines in vitro via ASH1L.For the exploration mechanism,we found ASH1L may promote an immunosuppressive microenvironment in HCC and ASH1L affects the expression of the cell junction protein zonula occludens-1,which is potentially relevant to the immune system.CONCLUSION Loss function of microRNA-142-3p induces cancer progression and immune evasion through upregulation of ASH1L in HCC.Both microRNA-142-3p and ASH1L can feature as new biomarker for HCC in the future.展开更多
Background Cisplatin （DDP） is one of most effective and most commonly used therapeutic agent in treating tumors,it can accumulate in the kidney and lead to acute renal failure.MicroRNA-181a can induce cell apoptosis...Background Cisplatin （DDP） is one of most effective and most commonly used therapeutic agent in treating tumors,it can accumulate in the kidney and lead to acute renal failure.MicroRNA-181a can induce cell apoptosis by suppressing the expression of Bcl-2 family.In the present study,we investigated the role of microRNA-181a in the apoptosis of tubular epithelial cell induced by DDP.Methods HK-2 cells were cultured,transfected with microRNA-181a inhibitor for 48 hours,and stimulated with 50 μmol/L cisplatin for 24 hours.MicroRNA-181a expression was analyzed by real time PCR,and cell apoptosis was detected by flow cytometry.Moreover,Bcl-2 and Bcl-2-associated X protein （Bax） expression were measured by Western blotting.Results MicroRNA-181a expression significantly down-regulated in cells transfected with microRNA-181a inhibitor,compared with that in untransfectd cells （21.19±2.01 vs.38.87±1.97,P 〈0.05）.Cell apoptosis induced by DDP significantly decreased in cells transfected with MicroRNA-181a inhibitor.Compared with DDP treated cells alone,Bcl-2 expression strikingly was up-regulated and Bax expression was down-regulated in cells transfected with microRNA-181a inhibitor.Conclusion One pathway of DDP induces apoptosis of tubular epithelial cell by suppressing Bcl-2 expression is achieved by regulating the target gene of MicroRNA-181a.展开更多
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supported by the National Natural Science Foundation of China(Nos.81702296,81772281)the Shandong Science and Technology Committee(Nos.2017GSF18124,ZR2019PC019,ZR2019MH022)+1 种基金the Health Commission of Shandong Province(Nos.2017WS737,2019KJK014)the Shandong Province Taishan Scholar Project(No.ts201712067).
文摘Tumor progression is usually characterized by proliferation,migration,and angiogenesis,which is essential for supplying both nutrients and oxygen to the tumor cells.Therefore,targeting angiogenesis has been considered a promising therapeutic strategy for cancer prevention and treatment.In the present study,we demonstrated that in addition to suppressing lung cancer cell proliferation and migration in vitro,10-hydroxycamptothecin(10-HCPT)is also capable of inhibiting angiogenesis in vivo with a miR-181a-dependent manner.Mechanistically,by upregulating miR-181a,which in turn downregulating FOXP1,10-HCPT can inhibit the PI3K/Akt/ERK signaling pathwaymediated angiogenesis.Furthermore,reduced levels of miR-181a have been found in both lung cancer cell lines and xenograft with concurrently elevated levels of FOXP1,VEGF,bFGF,and HDGF.Consistent with the findings from the in vitro experiments,miR-181a impairs neovascularization in our xenograft model.In summary,our findings have not only established the anti-oncogenic role of miR-181a in lung cancer angiogenesis but also suggest that 10-HCPT could be a potential therapeutic reagent for lung cancer treatment.
基金Supported by the Haihe Laboratory of Cell Ecosystem Innovation Fund,No.22HHXBJC00001the Key Discipline Special Project of Tianjin Municipal Health Commission,No.TJWJ2022XK016.
文摘BACKGROUND Hepatocellular carcinoma(HCC)has been a pervasive malignancy throughout the world with elevated mortality.Efficient therapeutic targets are beneficial to treat and predict the disease.Currently,the exact molecular mechanisms leading to the progression of HCC are still unclear.Research has shown that the microRNA-142-3p level decreases in HCC,whereas bioinformatics analysis of the cancer genome atlas database shows the ASH1L expression increased among liver tumor tissues.In this paper,we will explore the effects and mechanisms of microRNA-142-3p and ASH1L affect the prognosis of HCC patients and HCC cell bioactivity,and the association between them.AIM To investigate the effects and mechanisms of microRNA-142-3p and ASH1L on the HCC cell bioactivity and prognosis of HCC patients.METHODS In this study,we grouped HCC patients according to their immunohistochemistry results of ASH1L with pathological tissues,and retrospectively analyzed the prognosis of HCC patients.Furthermore,explored the roles and mechanisms of microRNA-142-3p and ASH1L by cellular and animal experiments,which involved the following experimental methods:Immunohistochemical staining,western blot,quantitative real-time-polymerase chain reaction,flow cytometric analysis,tumor xenografts in nude mice,etc.The statistical methods involved in this study contained t-test,one-way analysis of variance,theχ^(2)test,the Kaplan-Meier approach and the log-rank test.RESULTS In this study,we found that HCC patients with high expression of ASH1L possess a more recurrence rate as well as a decreased overall survival rate.ASH1L promotes the tumorigenicity of HCC and microRNA-142-3p exhibits reduced expression in HCC tissues and interacts with ASH1L through targeting the ASH1L 3′untranslated region.Furthermore,microRNA-142-3p promotes apoptosis and inhibits proliferation,invasion,and migration of HCC cell lines in vitro via ASH1L.For the exploration mechanism,we found ASH1L may promote an immunosuppressive microenvironment in HCC and ASH1L affects the expression of the cell junction protein zonula occludens-1,which is potentially relevant to the immune system.CONCLUSION Loss function of microRNA-142-3p induces cancer progression and immune evasion through upregulation of ASH1L in HCC.Both microRNA-142-3p and ASH1L can feature as new biomarker for HCC in the future.
基金This work was supported by the National Natural Science Foundation of China （No.61101218 and No.81102673）,the New Star Program of Beijing Science and Technology Commission （No.2011111） and the National Basic Research Program of China （No.2011 CB944004）.
文摘Background Cisplatin （DDP） is one of most effective and most commonly used therapeutic agent in treating tumors,it can accumulate in the kidney and lead to acute renal failure.MicroRNA-181a can induce cell apoptosis by suppressing the expression of Bcl-2 family.In the present study,we investigated the role of microRNA-181a in the apoptosis of tubular epithelial cell induced by DDP.Methods HK-2 cells were cultured,transfected with microRNA-181a inhibitor for 48 hours,and stimulated with 50 μmol/L cisplatin for 24 hours.MicroRNA-181a expression was analyzed by real time PCR,and cell apoptosis was detected by flow cytometry.Moreover,Bcl-2 and Bcl-2-associated X protein （Bax） expression were measured by Western blotting.Results MicroRNA-181a expression significantly down-regulated in cells transfected with microRNA-181a inhibitor,compared with that in untransfectd cells （21.19±2.01 vs.38.87±1.97,P 〈0.05）.Cell apoptosis induced by DDP significantly decreased in cells transfected with MicroRNA-181a inhibitor.Compared with DDP treated cells alone,Bcl-2 expression strikingly was up-regulated and Bax expression was down-regulated in cells transfected with microRNA-181a inhibitor.Conclusion One pathway of DDP induces apoptosis of tubular epithelial cell by suppressing Bcl-2 expression is achieved by regulating the target gene of MicroRNA-181a.
