ABSTRACT
Colon cancer (CC) is one of the leading causes of cancerrelated mortality in China and western countries. Several studies have demonstrated that long noncoding RNAs (lncRNAs) play critical roles in cancer development. However, the function of lncRNA RP11619L19.2 in colon cancer remains unclear. The aim of the present study was to investigate the expression pattern, function and underlying mechanism of action of RP11619L19.2 in CC development and metastasis. RP11619L19.2 was found to be highly expressed in CC tissues and cell lines, and it was associated with advanced TNM stage and lymph node metastasis. Furthermore, knockdown of RP11619L19.2 inhibited CC cell proliferation, migration, invasion and epithelialtomesenchymal transition (EMT). It was also observed that RP11619L19.2 was reciprocally repressed by miR12715p. Of note, miR12715p negatively regulated CD164 expression by directly targeting the 3'untranslated region of CD164. Overexpression of CD164 reversed the antimetastatic activity of RP11619L19.2 knockdown in CC cells. Mechanistically, it was demonstrated that lncRNA RP11619L19.2 played an oncogenic role and promoted CC development and metastasis by regulating the miR12715p/CD164 axis and EMT. In conclusion, the findings of the present study indicated that RP11619L19.2 regulates CD164 expression and EMT by sponging miR12715p, which may provide novel targets for lncRNAdirected diagnosis and therapy for patients with CC.
Subject(s)
Colonic Neoplasms/genetics , MicroRNAs/metabolism , RNA, Long Noncoding/metabolism , 3' Untranslated Regions/genetics , Cell Line, Tumor , Cell Movement/drug effects , Cell Movement/genetics , Cell Proliferation/drug effects , Cell Proliferation/genetics , China , Colon/pathology , Colonic Neoplasms/pathology , Endolyn/genetics , Epithelial-Mesenchymal Transition/drug effects , Epithelial-Mesenchymal Transition/genetics , Gene Expression Regulation, Neoplastic/drug effects , Gene Expression Regulation, Neoplastic/genetics , Gene Knockdown Techniques , Humans , Intestinal Mucosa/pathology , MicroRNAs/agonists , MicroRNAs/antagonists & inhibitors , RNA, Long Noncoding/geneticsABSTRACT
The transmembrane protease, serine 3 (TMPRSS3), a member of the type II transmembrane serine protease family, plays an important role in mediating tissue development, homeostasis and various biological processes. Recently, TMPRSS3 has been reported to be involved in cancer progression. However, the role of TMPRSS3 in gastric cancer (GC) remains largely unknown. In this study, we found that TMPRSS3 was highly expressed in GC tissues and cell lines. Knockdown of TMPRSS3 inhibited GC cell proliferation, invasion and epithelial-mesenchymal transition (EMT) in vitro as well as suppressed GC cell growth and dissemination in vivo. These inhibitory effects were mediated by regulation of the ERK1/2 signaling pathway. Moreover, TMPRSS3-mediated ERK1/2 activation was dependent on the PI3K/Akt pathway. In conclusion, TMPRSS3 contributed to GC progression via activation of the PI3K/Akt/ERK signaling pathway and might act as a therapeutic target for GC treatment.
Subject(s)
Epithelial-Mesenchymal Transition , Gene Knockdown Techniques , MAP Kinase Signaling System , Membrane Proteins/genetics , Neoplasm Proteins/genetics , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Serine Endopeptidases/genetics , Stomach Neoplasms/pathology , Animals , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Female , Gene Expression Regulation, Neoplastic , Humans , Male , Membrane Proteins/metabolism , Mice, Inbred BALB C , Mice, Nude , Middle Aged , Neoplasm Invasiveness , Neoplasm Proteins/metabolism , Serine Endopeptidases/metabolism , Stomach Neoplasms/geneticsABSTRACT
OBJECTIVE: To investigate the role of vascular endothelial growth factor (VEGF) in the pathogenesis of severe acute pancreatitis (SAP) in rats. METHODS: Sixty-four male SD rats were randomly divided into control group and SAP group, and in the latter group, SAP was induced by retrograde injection of 5% sodium taurocholate in the pancreaticobiliary duct. The rats were sacrificed at 1, 3, 6 and 12 h after the operation, and the severity of pancreatitis was assessed according to histological scoring. The serum levels of VEGF were examined with enzyme-linked immunosorbent assay, and the expression of VEGF in the pancreatic tissues was measured by SP immunohistochemistry. Another 30 SD rats were randomized into the control group, SAP group and SAP+recombinant rat VEGF injection group, and the vascular permeability of the pancreatic microcirculation was determined by Evans Blue leakage test. RESULTS: At each of the time points for measurement, both the serum VEGF level and scores of pancreatic tissue injury were significantly higher in SAP group than in the control group (P<0.05). Compared with the control group, the expressions of VEGF in the pancreatic tissues of SAP group were significantly up-regulated following the operation (P<0.05). The vascular permeability of the pancreatic microcirculation significantly increased after the onset of SAP, and injection of recombinant rat VEGF significantly increased the leakage rate of Evans Blue. CONCLUSION: VEGF may play an important role in the pathogenesis of pancreatitis and in causing edema and hemorrhage in SAP, and the level of serum VEGF may reflect the severity of pancreatic injury.
Subject(s)
Capillary Permeability/physiology , Pancreatitis/metabolism , Vascular Endothelial Growth Factor A/blood , Acute Disease , Animals , Biomarkers , Male , Pancreatitis/pathology , Random Allocation , Rats , Rats, Sprague-DawleyABSTRACT
OBJECTIVE: To investigate the protective effects of captopril against lung injury in a rat model of severe acute pancreatitis (SAP). METHODS: Seventy-two male SD rats were randomized into sham-operated group (SO group), SAP group and captopril intervention group (CAP group). Serum amylase and myeloperoxidase (MPO) activity in the lung tissue were examined at 1, 6 and 12 h after the operation. TNF-α and AngII in the lung tissue were detected by ELISA, and the histopathological changes of the pancreas and lung were observed microscopically. RESULTS: The MPO activity , which was similar between SAP group and CAP group at 1 h, were significantly lowered in CAP group at 6 and 12 h (P<0.05). Serum amylase level and the levels of TNF-α and AngII in the lung tissue homogenate were all reduced significantly in CAP group as compared to those in SAP group (P<0.01). The pathological injury of the lung was obviously lessened in CAP group in comparison with that in SAP group. CONCLUSION: Captopril can ameliorate SAP-induced lung injury in rats.
Subject(s)
Captopril/pharmacology , Lung Injury/prevention & control , Pancreatitis/complications , Amylases/blood , Angiotensin II/metabolism , Animals , Captopril/therapeutic use , Disease Models, Animal , Lung/metabolism , Lung/pathology , Lung Injury/etiology , Male , Pancreatitis/drug therapy , Peroxidase/metabolism , Rats , Rats, Sprague-Dawley , Tumor Necrosis Factor-alpha/metabolismABSTRACT
AIM: To observe the effect of proteasome inhibitor MG-132 on severe acute pancreatitis (SAP) and associated lung injury of rats. METHODS: Male adult SD rats were randomly divided into SAP group, sham-operation group, and MG-132 treatment group. A model of SAP was established by injection of 5% sodium taurocholate into the biliary-pancreatic duct of rats. The MG-132 group was pretreated with 10 mg/kg MG-132 intraperitoneally (ip) 30 min before the induction of pancreatitis. The changes in serum amylase, myeloperoxidase (MPO) activity of pancreatic and pulmonary tissue were measured. The TNF-alpha level in pancreatic cytosolic fractions was assayed with an enzyme-linked immunosorbent assay (ELISA) kit. Meanwhile, the pathological changes in both pancreatic and pulmonary tissues were also observed. RESULTS: MG-132 significantly decreased serum amylase, pancreatic weight/body ratio, pancreatic TNF-alpha level, pancreatic and pulmonary MPO activity (P < 0.05). Histopathological examinations revealed that pancreatic and pulmonary samples from rats pretreated with MG-132 demonstrated milder edema, cellular damage, and inflammatory activity (P < 0.05). CONCLUSION: The proteasome inhibitor MG-132 shows a protective effect on severe acute pancreatitis and associated lung injury of rats.
Subject(s)
Cysteine Proteinase Inhibitors/pharmacology , Leupeptins/pharmacology , Lung Diseases/prevention & control , Lung/drug effects , Pancreas/drug effects , Pancreatitis/prevention & control , Proteasome Inhibitors , Acute Disease , Amylases/blood , Animals , Disease Models, Animal , Enzyme-Linked Immunosorbent Assay , Lung/enzymology , Lung/pathology , Lung Diseases/enzymology , Lung Diseases/etiology , Male , Organ Size , Pancreas/enzymology , Pancreas/pathology , Pancreatitis/chemically induced , Pancreatitis/complications , Pancreatitis/enzymology , Peroxidase/metabolism , Proteasome Endopeptidase Complex/metabolism , Rats , Rats, Sprague-Dawley , Severity of Illness Index , Taurocholic Acid , Tumor Necrosis Factor-alpha/metabolismABSTRACT
OBJECTIVE: To observe the protective effect of the proteasome inhibitor MG-132 in rats with severe acute pancreatitis (SAP) and the associated lung injury. METHODS: In rat models of the SAP established with injection of 5% sodium taurocholate into the biliary-pancreatic duct, the changes of the serum amylase and myeloperoxidase (MPO) activity in the pancreatic and lung tissues were evaluated. The pathological changes of the pancreatic and lung tissues were also observed. RESULTS: MG-132 significantly decreased serum amylase, pancreatic weight/body weight ratio, and pancreatic and pulmonary myeloperoxidase activity (P<0.05). Histopathological examinations revealed milder edema, cellular damage, and inflammation in the pancreatic and lung tissues of rats pretreated with the peptide (P<0.05). CONCLUSION: MG-132 ameliorates SAP and the associated lung injury in rats.
