To confirm the relationship between Circ_0003855 and EC,we purchased the Human esophageal carcinoma cell line Eca109 and normal human esophageal epithelial cells HEEC,and the expression levels of Circ_0003855,miR-622,...To confirm the relationship between Circ_0003855 and EC,we purchased the Human esophageal carcinoma cell line Eca109 and normal human esophageal epithelial cells HEEC,and the expression levels of Circ_0003855,miR-622,and FLOT1 were detected.The results show that Circ_0003855 and FLOT1 were highly expressed in Eca109 cells,while miR-622 was lowly expressed(p<0.05).Subsequently,Circ_0003855 small interfering RNA(si-Circ_0003855)and its negative control(si-NC)were used to detect changes in cellular biological behaviors.We found that the activity of Eca109 cells was reduced after interfering with the expression of Circ_0003855,and miR-622 expression was elevated,while FLOT1 was decreased(p<0.05).Additionally,si-Circ_0003855 and miR-622 inhibitor sequence(miR-622-inhibition)were co-transfected into cells with miR-622-inhibition alone,and untreated Eca109 cells were used as a control to detect the expression of FLOT1.Co-transfection of si-Circ_0003855 and miR-622-inhibition showed no significant difference in FLOT1 expression compared to the control cells(p>0.05).Synthesizing the results of these experiments above,we believe that interfering with the expression of Circ_0003855 can inhibit the activity of EC cells,and its mechanism is related to miR-622 and FLOT1.展开更多
BACKGROUND Increasing data indicated that long noncoding RNAs(lncRNAs)were directly or indirectly involved in the occurrence and development of tumors,including hepatocellular carcinoma(HCC).Recent studies had found t...BACKGROUND Increasing data indicated that long noncoding RNAs(lncRNAs)were directly or indirectly involved in the occurrence and development of tumors,including hepatocellular carcinoma(HCC).Recent studies had found that the expression of lncRNA HAND2-AS1 was downregulated in HCC tissues,but its role in HCC progression is unclear.Ultrasound targeted microbubble destruction mediated gene transfection is a new method to overexpress genes.AIM To study the role of ultrasound microbubbles(UTMBs)mediated HAND2-AS1 in the progression of HCC,in order to provide a new reference for the treatment of HCC.METHODS In vitro,we transfected HAND2-AS1 siRNA into HepG2 cells by UTMBs,and detected cell proliferation,apoptosis,invasion and epithelial-mesenchymal transition(EMT)by cell counting kit-8 assay,flow cytometry,Transwell invasion assay and Western blotting,respectively.In addition,we transfected miR-837-5p mimic into UTMBs treated cells and observed the changes of cell behavior.Next,the UTMBs treated HepG2 cells were transfected together with miR-837-5p mimic and tissue inhibitor of matrix metalloproteinase-2(TIMP2)overexpression vector,and we detected cell proliferation,apoptosis,invasion and EMT.In vivo,we established a mouse model of subcutaneous transplantation of HepG2 cells and observed the effect of HAND2-AS1 silencing on tumor formation ability.RESULTS We found that UTMBs carrying HAND2-AS1 restricted cell proliferation,invasion,and EMT,encouraged apoptosis,and HAND2-AS1 silencing eliminated the effect of UTMBs.Additionally,miR-873-5p targets the gene HAND2-AS1,which also targets the 3’UTR of TIMP2.And miR-873-5p mimic counteracted the impact of HAND2-AS1.Further,miR-873-5p mimic solely or in combination with pcDNA-TIMP2 had been transformed into HepG2 cells exposed to UTMBs.We discovered that TIMP2 reversed the effect of miR-873-5p mimic caused by the blocked signalling cascade for matrix metalloproteinase(MMP)2/MMP9.In vivo results showed that HAND2-AS1 silencing significantly inhibited tumor formation in mice.CONCLUSION LncRNA HAND2-AS1 promotes TIMP2 expression by targeting miR-873-5p to inhibit HepG2 cell growth and delay HCC progression.展开更多
AIM:To evaluate the biological and clinical characteristics of miR-622 in gastric cancer. METHODS:We analyzed the expression of miR-622 in 57 pair matched gastric neoplastic and adjacent non-neoplastic tissues by quan...AIM:To evaluate the biological and clinical characteristics of miR-622 in gastric cancer. METHODS:We analyzed the expression of miR-622 in 57 pair matched gastric neoplastic and adjacent non-neoplastic tissues by quantitative real-time polymerase chain reaction. Functional analysis of miR-622 expression was assessed in vitro in gastric cancer cell lines with miR-622 precursor and inhibitor. The roles of miR-622 in tumorigenesis and tumor metastasis were analyzed using a stable miR-622 expression plasmid in nude mice. A luciferase reporter assay was used to assess the effect of miR-622 on inhibitor of growth family,member 1 (ING1) expression. RESULTS:Expression of miR-622 was down-regulated in gastric cancer. MiR-622 was found involved in differentia-tion and lymphatic metastasis in human gastric cancer. Ectopic expression of miR-622 promoted invasion,tumorigenesis and metastasis of gastric cancer cells both in vitro and in vivo. ING1 is a direct target of miR-622. CONCLUSION:These findings help clarify the molecular mechanisms involved in gastric cancer metastasis and indicate that miR-622 modulation may be a bona fide treatment of gastric cancer.展开更多
In recent years histone deacetylase inhibitors (HDACi’s) have emerged as promising therapeutics for cancer. While favorable responses to HDACi’s as single agents have been shown in several hematological malignancies...In recent years histone deacetylase inhibitors (HDACi’s) have emerged as promising therapeutics for cancer. While favorable responses to HDACi’s as single agents have been shown in several hematological malignancies, very little efficacy has been demonstrated in solid tumors. c-Myc (Myc), an oncoprotein commonly over-expressed in cancer, has been shown by several studies to play a critical role in HDACi-mediated cellular death. To expand upon these findings and determine the role that Myc plays in this process in solid tumors, we compared the effect of two HDAC inhibitors, SAHA and LAQ824, on the proliferation of solid tumor cell lines expressing high versus low levels of Myc. We found that cells expressing high levels of Myc were more sensitive to HDACi. In addition, there were significant differences in the type of response to HDACi treatment between the two cell types with prominent apoptosis in cells expressing higher levels of Myc while cell cycle arrest was more commonly observed in cells expressing lower levels of Myc. Interestingly, HDACi reduced the expression of Myc and one of its well-known oncogenic miRNA targets, miR-17~92 cluster, resulting in an increase in the expression of the master pro-apoptotic protein Bim. We propose that this novel mechanism may play a role in the potent anti-proliferative effects mediated by HDACi. Furthermore, these studies suggest that Myc expression could be used as a predictive biomarker to select patients with solid tumors who may be more responsive to HDACi treatment.展开更多
AIM To investigate the underlying molecularmechanisms of miR-451 to inhibit proliferation ofesophageal carcinoma cell line EC9706.METHODS： Assays for cell growth, apoptosis andinvasion were used to evaluate the effec...AIM To investigate the underlying molecularmechanisms of miR-451 to inhibit proliferation ofesophageal carcinoma cell line EC9706.METHODS： Assays for cell growth, apoptosis andinvasion were used to evaluate the effects of miR-451expression on EC cells. Luciferase reporter and Westernblot assays were used to test whether cyclin-dependentkinase inhibitor 2D （CDKN2D） and MAP3K1 act as majortargets of miR-451.RESULTS： The results showed that CDKN2D andMAP3K1 are direct targets of miR-451. CDKN2D andMAP3K1 overexpression reversed the effect of miR-451.MiR-451 inhibited the proliferation of EC9706 bytargeting CDKN2D and MAP3K1.CONCLUSION： These findings suggest that miR-451might be a novel prognostic biomarker and a potentialtarget for the treatment of esophageal squamous cellcarcinoma in the future.展开更多
文摘To confirm the relationship between Circ_0003855 and EC,we purchased the Human esophageal carcinoma cell line Eca109 and normal human esophageal epithelial cells HEEC,and the expression levels of Circ_0003855,miR-622,and FLOT1 were detected.The results show that Circ_0003855 and FLOT1 were highly expressed in Eca109 cells,while miR-622 was lowly expressed(p<0.05).Subsequently,Circ_0003855 small interfering RNA(si-Circ_0003855)and its negative control(si-NC)were used to detect changes in cellular biological behaviors.We found that the activity of Eca109 cells was reduced after interfering with the expression of Circ_0003855,and miR-622 expression was elevated,while FLOT1 was decreased(p<0.05).Additionally,si-Circ_0003855 and miR-622 inhibitor sequence(miR-622-inhibition)were co-transfected into cells with miR-622-inhibition alone,and untreated Eca109 cells were used as a control to detect the expression of FLOT1.Co-transfection of si-Circ_0003855 and miR-622-inhibition showed no significant difference in FLOT1 expression compared to the control cells(p>0.05).Synthesizing the results of these experiments above,we believe that interfering with the expression of Circ_0003855 can inhibit the activity of EC cells,and its mechanism is related to miR-622 and FLOT1.
文摘BACKGROUND Increasing data indicated that long noncoding RNAs(lncRNAs)were directly or indirectly involved in the occurrence and development of tumors,including hepatocellular carcinoma(HCC).Recent studies had found that the expression of lncRNA HAND2-AS1 was downregulated in HCC tissues,but its role in HCC progression is unclear.Ultrasound targeted microbubble destruction mediated gene transfection is a new method to overexpress genes.AIM To study the role of ultrasound microbubbles(UTMBs)mediated HAND2-AS1 in the progression of HCC,in order to provide a new reference for the treatment of HCC.METHODS In vitro,we transfected HAND2-AS1 siRNA into HepG2 cells by UTMBs,and detected cell proliferation,apoptosis,invasion and epithelial-mesenchymal transition(EMT)by cell counting kit-8 assay,flow cytometry,Transwell invasion assay and Western blotting,respectively.In addition,we transfected miR-837-5p mimic into UTMBs treated cells and observed the changes of cell behavior.Next,the UTMBs treated HepG2 cells were transfected together with miR-837-5p mimic and tissue inhibitor of matrix metalloproteinase-2(TIMP2)overexpression vector,and we detected cell proliferation,apoptosis,invasion and EMT.In vivo,we established a mouse model of subcutaneous transplantation of HepG2 cells and observed the effect of HAND2-AS1 silencing on tumor formation ability.RESULTS We found that UTMBs carrying HAND2-AS1 restricted cell proliferation,invasion,and EMT,encouraged apoptosis,and HAND2-AS1 silencing eliminated the effect of UTMBs.Additionally,miR-873-5p targets the gene HAND2-AS1,which also targets the 3’UTR of TIMP2.And miR-873-5p mimic counteracted the impact of HAND2-AS1.Further,miR-873-5p mimic solely or in combination with pcDNA-TIMP2 had been transformed into HepG2 cells exposed to UTMBs.We discovered that TIMP2 reversed the effect of miR-873-5p mimic caused by the blocked signalling cascade for matrix metalloproteinase(MMP)2/MMP9.In vivo results showed that HAND2-AS1 silencing significantly inhibited tumor formation in mice.CONCLUSION LncRNA HAND2-AS1 promotes TIMP2 expression by targeting miR-873-5p to inhibit HepG2 cell growth and delay HCC progression.
基金Supported by Grants from Science Foundation of Shandong Province of China (2003-23)Key Research Project from Shan-dong Science and Technology Commission, No. 2005GG3202066
文摘AIM:To evaluate the biological and clinical characteristics of miR-622 in gastric cancer. METHODS:We analyzed the expression of miR-622 in 57 pair matched gastric neoplastic and adjacent non-neoplastic tissues by quantitative real-time polymerase chain reaction. Functional analysis of miR-622 expression was assessed in vitro in gastric cancer cell lines with miR-622 precursor and inhibitor. The roles of miR-622 in tumorigenesis and tumor metastasis were analyzed using a stable miR-622 expression plasmid in nude mice. A luciferase reporter assay was used to assess the effect of miR-622 on inhibitor of growth family,member 1 (ING1) expression. RESULTS:Expression of miR-622 was down-regulated in gastric cancer. MiR-622 was found involved in differentia-tion and lymphatic metastasis in human gastric cancer. Ectopic expression of miR-622 promoted invasion,tumorigenesis and metastasis of gastric cancer cells both in vitro and in vivo. ING1 is a direct target of miR-622. CONCLUSION:These findings help clarify the molecular mechanisms involved in gastric cancer metastasis and indicate that miR-622 modulation may be a bona fide treatment of gastric cancer.
文摘In recent years histone deacetylase inhibitors (HDACi’s) have emerged as promising therapeutics for cancer. While favorable responses to HDACi’s as single agents have been shown in several hematological malignancies, very little efficacy has been demonstrated in solid tumors. c-Myc (Myc), an oncoprotein commonly over-expressed in cancer, has been shown by several studies to play a critical role in HDACi-mediated cellular death. To expand upon these findings and determine the role that Myc plays in this process in solid tumors, we compared the effect of two HDAC inhibitors, SAHA and LAQ824, on the proliferation of solid tumor cell lines expressing high versus low levels of Myc. We found that cells expressing high levels of Myc were more sensitive to HDACi. In addition, there were significant differences in the type of response to HDACi treatment between the two cell types with prominent apoptosis in cells expressing higher levels of Myc while cell cycle arrest was more commonly observed in cells expressing lower levels of Myc. Interestingly, HDACi reduced the expression of Myc and one of its well-known oncogenic miRNA targets, miR-17~92 cluster, resulting in an increase in the expression of the master pro-apoptotic protein Bim. We propose that this novel mechanism may play a role in the potent anti-proliferative effects mediated by HDACi. Furthermore, these studies suggest that Myc expression could be used as a predictive biomarker to select patients with solid tumors who may be more responsive to HDACi treatment.
基金Supported by National Natural Science Foundation of China,No.81301726
文摘AIM To investigate the underlying molecularmechanisms of miR-451 to inhibit proliferation ofesophageal carcinoma cell line EC9706.METHODS： Assays for cell growth, apoptosis andinvasion were used to evaluate the effects of miR-451expression on EC cells. Luciferase reporter and Westernblot assays were used to test whether cyclin-dependentkinase inhibitor 2D （CDKN2D） and MAP3K1 act as majortargets of miR-451.RESULTS： The results showed that CDKN2D andMAP3K1 are direct targets of miR-451. CDKN2D andMAP3K1 overexpression reversed the effect of miR-451.MiR-451 inhibited the proliferation of EC9706 bytargeting CDKN2D and MAP3K1.CONCLUSION： These findings suggest that miR-451might be a novel prognostic biomarker and a potentialtarget for the treatment of esophageal squamous cellcarcinoma in the future.
