ABSTRACT
Colorectal cancer is one of the most common malignancies. Previous studies have reported that cortactin (CTTN) is often overexpressed in tumors and is associated with metastasis and poor prognosis of patients. The abnormal expression of microRNAs (miRNAs or miRs) is closely related to the development and progression of various types of cancer, including colorectal cancer. However, little is known about the miRNAs targeting cortactin. In the present study, prediction using biological software revealed that cortactin has binding sites for miR-542-3p. Transfection with miR-542-3p mimic demonstrated that miR542-3p reduced the expression of cortactin in colorectal cancer cells. Dual luciferase reporter assays further demonstrated that miR-542-3p regulated cortactin in a targeted manner and that miR-542-3p expression was significantly downregulated in colorectal cancer cells. A cell proliferation assay and Transwell migration assay were undertaken: we noted that miR542-3p inhibited the proliferation and invasion of colorectal cancer cells while promoting their apoptosis. By contrast, cortactin acted antagonistically. When co-transfected with miR-542-3p mimic and CTTN overexpression vector, the inhibitory effect of miR-542-3p was blocked. This indicates that miR-542-3p regulates CTTN in a targeted manner to modulate the growth and invasion of colorectal cancer cells. The present study thus provides new targets for the prevention and treatment of colorectal cancer.
Subject(s)
Colorectal Neoplasms/genetics , Cortactin/genetics , Gene Expression Regulation, Neoplastic , MicroRNAs/genetics , Neoplasm Invasiveness/genetics , Apoptosis , Cell Line, Tumor , Cell Movement , Cell Proliferation , Colon/metabolism , Colon/pathology , Colorectal Neoplasms/pathology , Humans , Neoplasm Invasiveness/pathology , Rectum/metabolism , Rectum/pathology , TransfectionABSTRACT
OBJECTIVE: To explore the effect of rosiglitazone on the activity of signal transducer and activator of transcription 1 in rats with severe acute pancreatitis. METHODS: Fifty-four male Wistar rats were randomly allocated into three groups (n = 18). SO group: sham-operated animals served as control, operation was executed and sodium chloride but not sodium taurocholate was injected. SAP group: SAP was induced by the retrograde injection of 5% sodium taurocholate into the biliopancreatic duct. ROSI group: same as SAP group, but rosiglitazone (6 mg/kg) was administered intravenously 30 min before operation. Rats in each group were sacrificed at 3,6 and 12 h after operation. The levels of serum amylase and histologic scores of pancreatic tissue were measured. The expression of TNF-alpha mRNA in pancreatic tissue were determined by reverse transcription-polymerase chain reaction (RT-PCR). The expression of phosphorylated STAT1 in pancreatic tissue was assayed by immunohistochemistry. RESULTS: Compared to SO group, the levels of serum amylase and phosphorylated STAT1, TNF-alpha mRNA and histologic scores of pancreatic tissue were significantly elevated at the same time points after SAP (P < 0.01). The levels of these detection in ROSI group were lower than those of the SAP group at the same time points (P < 0.05), but higher than SO group (P < 0.05). CONCLUSIONS: STAT1 was activated in severe acute pancreatitis. Rosiglitazone has a protective effects in rats with severe acute pancreatitis. The mechanism of its protective effects maybe that it inhibits the activation of JAK/STAT pathway, which can down-regulate the expression of TNF-alpha mRNA and block the the inflammatory cascade partially.