ABSTRACT
The mortality rate of clear cell renal cell carcinoma (ccRCC) remains high. Immunohistochemical staining, Western blotting and real-time quantitative polymerase chain reaction were employed to evaluate ADAM (a disintegrin and metalloproteinase) metallopeptidase with thrombospondin type 1 motif 16 (ADAMTS16) levels in ccRCC tissues and paired normal tissues, and all tissues were obtained from clinical samples of 46 cases of ccRCC patients. Moreover, we analyzed the role ADAMTS16 in the progression of ccRCC using Cell Counting Kit-8 assay and flow cytometry. ADAMTS16 levels in ccRCC tissues were markedly low, relative to normal tissues, and ADAMTS16 level closely correlated with tumor stage, lymph node metastasis as well as pathological grade. Patients with elevated ADAMTS16 expressions have a more favorable survival outcome, relative to patients with low expression of ADAMTS16. In vitro study showed ADAMTS16 expression markedly decreased in ccRCC cells and acted as a tumor suppressor compared with the normal cells. The expression of ADAMTS16 is down-regulated in ccRCC tissues, relative to normal tissues, and it may inhibit the malignancies of ccRCC. Such inhibitory effect may be ascribed to the involvement of AKT/mammalian target of rapamycin signaling. Hence, the present study of ADAMTS16 will provide new insight into the underlying biological mechanisms of ccRCC.
Subject(s)
Carcinoma, Renal Cell , Carcinoma , Kidney Neoplasms , Humans , Carcinoma, Renal Cell/pathology , Kidney Neoplasms/pathology , Thrombospondins/metabolism , Prognosis , Cell Line, Tumor , Cell Proliferation , Gene Expression Regulation, NeoplasticABSTRACT
OBJECTIVE: Herein, we purposed to explore the NRCAM expression in gastric cancer (GC) along with its clinical implication. METHODS: The TCGA dataset was utilized to analyze the expression coupled with the clinical worthiness of NRCAM in GC. The expressions of NRCAM were examined in clinical GC specimens via qRT-PCR along with western blotting. Moreover, we analyzed the role NRCAM in the progression of GC using flow cytometry, Wound-healing, CCK-8, as well as Transwell assays. EMT markers (E-cadherin, vimentin along with N-cadherin) protein expression were examined via western blotting. RESULTS: TCGA data resource revealed that NRCAM expression in GC tissues is much lower in contrast with normal tissues and patients with higher NRCAM expression showed poorer prognosis. In vitro study revealed that the over-expression NRCAM accelerated cell growth, migration, as well as infiltration while decreasing cell apoptosis but silencing of NRCAM had the opposite effect. Upregulation of NRCAM reduced E-cadherin contents, however elevated vimentin coupled with N-cadherin protein levels in GC cells. Nonetheless, NRCAM downregulation led to the opposite results. CONCLUSION: According to our findings, NRCAM is an oncogene with the potential to works as a prognostic biomarker and treatment target for GC.
Subject(s)
Stomach Neoplasms , Cadherins/genetics , Cadherins/metabolism , Cell Adhesion Molecules/metabolism , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Epithelial-Mesenchymal Transition/genetics , Gene Expression Regulation, Neoplastic/genetics , Humans , Neoplasm Invasiveness , Prognosis , Stomach Neoplasms/metabolism , Vimentin/genetics , Vimentin/metabolismABSTRACT
OBJECTIVE: To investigate the effects of gastric bypass surgery(GBP) on hepatic phosphoenolpyruvate carboxykinase(PEPCK) mRNA expression in type 2 diabetic Goto-Kakizaki rats. METHODS: Male GK rats were randomized into three groups: gastric bypass surgery(n=10), sham operation with diet restriction(n=10), and sham operation alone(n=10). Liver specimens of GK rats were collected during the intraoperative period for self-control study and 8 weeks after surgery. Fasting blood glucose, food intake, and body weight were recorded before surgery and 1, 2, 4, 8 weeks after surgery. The expression of PEPCK mRNA was measured by real-time PCR. RESULTS: The fasting plasma glucose level decreased from(17.6±2.1) mmol/L before surgery to(7.5±0.9) mmol/L 8 weeks after surgery in GBP group. The level of PEPCK mRNA decreased from 1.08±0.38 before surgery to 0.41±0.10 8 weeks after surgery, significantly lower than that in sham operation alone group(1.04±0.12)(P<0.01). The level of PEPCK mRNA in diet restriction group increased from 1.15±0.16 before surgery to 2.54±0.82 8 weeks after surgery(P<0.01). The expression of PEPCK mRNA in diet restriction was significantly higher than that in CBP group(P<0.01). CONCLUSIONS: GBP can significantly improve hyperglycemia in type 2 diabetic GK rat models, which may be associated with the decrease of hepatic PEPCK mRNA level.