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
BACKGROUND Gastric variceal hemorrhage is one of the primary manifestations of left-sided portal hypertension(LSPH).The hemorrhage is fatal and requires safe and effective interventions.AIM To evaluate the clinical sa...BACKGROUND Gastric variceal hemorrhage is one of the primary manifestations of left-sided portal hypertension(LSPH).The hemorrhage is fatal and requires safe and effective interventions.AIM To evaluate the clinical safety and efficacy of modified endoscopic ultrasound(EUS)-guided selective N-butyl-2-cyanoacrylate(NBC)injections for gastric variceal hemorrhage in LSPH.METHODS A retrospective observational study of patients with LSPH-induced gastric variceal hemorrhage was conducted.Preoperative EUS evaluations were performed.Enrolled patients were divided into modified and conventional groups according to the NBC injection technique.The final selection of NBC injection technique depended on the patients’preferences and clinical status.The technical and clinical success rates,operation time,NBC doses,perioperative complications,postoperative hospital stay,and recurrent bleeding rates were analyzed,respectively.RESULTS A total of 27 patients were enrolled.No statistically significant differences were observed between the two groups regarding baseline characteristics.In comparison to patients in the conventional group,patients in the modified group demonstrated significantly reduced NBC doses(2.0±0.6 mL vs 3.1±1.0 mL;P=0.004)and increased endoscopic operation time(71.9±11.9 min vs 22.5±6.7 min;P<0.001).Meanwhile,the two groups had no significant difference in the technical and clinical success rates,perioperative complications,postoperative hospital stay,and recurrent bleeding rates.CONCLUSION Modified EUS-guided selective NBC injections demonstrated safety and efficacy for LSPH-induced gastric variceal hemorrhage,with advantages of reduced injection dose and no radiation risk.Drawbacks were time consumption and technical challenge.展开更多
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Program for Youth Innovation in Future Medicine,Chongqing Medical University,China,No.W0138.
文摘BACKGROUND Gastric variceal hemorrhage is one of the primary manifestations of left-sided portal hypertension(LSPH).The hemorrhage is fatal and requires safe and effective interventions.AIM To evaluate the clinical safety and efficacy of modified endoscopic ultrasound(EUS)-guided selective N-butyl-2-cyanoacrylate(NBC)injections for gastric variceal hemorrhage in LSPH.METHODS A retrospective observational study of patients with LSPH-induced gastric variceal hemorrhage was conducted.Preoperative EUS evaluations were performed.Enrolled patients were divided into modified and conventional groups according to the NBC injection technique.The final selection of NBC injection technique depended on the patients’preferences and clinical status.The technical and clinical success rates,operation time,NBC doses,perioperative complications,postoperative hospital stay,and recurrent bleeding rates were analyzed,respectively.RESULTS A total of 27 patients were enrolled.No statistically significant differences were observed between the two groups regarding baseline characteristics.In comparison to patients in the conventional group,patients in the modified group demonstrated significantly reduced NBC doses(2.0±0.6 mL vs 3.1±1.0 mL;P=0.004)and increased endoscopic operation time(71.9±11.9 min vs 22.5±6.7 min;P<0.001).Meanwhile,the two groups had no significant difference in the technical and clinical success rates,perioperative complications,postoperative hospital stay,and recurrent bleeding rates.CONCLUSION Modified EUS-guided selective NBC injections demonstrated safety and efficacy for LSPH-induced gastric variceal hemorrhage,with advantages of reduced injection dose and no radiation risk.Drawbacks were time consumption and technical challenge.